Nitrogen-containing heterocyclic compounds, pharmaceutically acceptable salts thereof, and methods for their preparation and use.

Abstract

This invention discloses nitrogen-containing heterocyclic compounds, pharmaceutically acceptable salts thereof, and methods for preparing and using them. The invention provides compounds represented by formula (I) or pharmaceutically acceptable salts thereof. The compounds of the present invention can be used as muscarinic receptor positive allosteric modulators, and the compounds of the present invention can treat diseases mediated by (or associated with) M receptors. [Formula 1] JPEG2026515254000633.jpg10169

Description

[Technical Field]

[0001] This application claims priority to Chinese patent application 202211339268.9, filed on 28 October 2022, and this application incorporates the entire text of the aforementioned Chinese patent application.

[0002] This application claims priority to Chinese Patent Application No. 202211686868.2, filed on December 26, 2022, and this application incorporates the entire text of the aforementioned Chinese Patent Application.

[0003] This application claims priority to Chinese patent application 202310099794.0, filed on 08 February 2023, and this application incorporates the entire text of the aforementioned Chinese patent application.

[0004] This application claims priority to Chinese Patent Application No. 202310186197.1, filed on March 1, 2023, and this application incorporates the entire text of the aforementioned Chinese Patent Application.

[0005] This application claims priority to Chinese Patent Application No. 202310263463.6, filed on March 17, 2023, and this application incorporates the entire text of the aforementioned Chinese Patent Application.

[0006] This application claims priority to Chinese patent application 202310719553.1, filed on June 16, 2023, and this application incorporates the entire text of the aforementioned Chinese patent application.

[0007] This application claims priority to Chinese Patent Application No. 202311378324.4, filed on October 23, 2023, and this application incorporates the entire text of the aforementioned Chinese Patent Application.

[0008] This invention relates to nitrogen-containing heterocyclic compounds, pharmaceutically acceptable salts thereof, and methods for preparing and using them. [Background technology]

[0009] Muscarinic receptors (M receptors) belong to the G protein-coupled receptor class and are a type of acetylcholine receptor. There are five subtypes of M receptors: M1, M3, and M5 bind to the Gq protein, activating phospholipase C and increasing intracellular calcium levels. M2 and M4 bind to the Gi protein, inhibiting adenylyl cyclase and decreasing cAMP levels. M1 receptors are distributed throughout the central nervous system, digestive system, and lymphoid tissues, and as the major subtype of M receptors, they can regulate both cellular excitability and cholinergic transmission. M4 receptors are mainly located in the cortex, hippocampus, and striatum, playing a crucial role in regulating dopamine release and motor activity, but they do not regulate important peripheral physiological functions (Neuropharmacology 2018, 136, 362).

[0010] M receptor agonists have been widely studied by numerous scientific research institutions and pharmaceutical companies as treatments for mental disorders. For example, xanomeline, an M1 / M4 receptor agonist, underwent a Phase II clinical trial in the 1990s to treat Alzheimer's disease. While patients' cognitive function improved after treatment with this drug, serious toxic side effects were observed in the peripheral and gastrointestinal tract. KarXT, a drug for treating schizophrenia developed by Karuna, consists of xanomeline and the M1 receptor antagonist trospium. A recent Phase II clinical trial showed that the KarXT treatment group achieved significantly improved Positive and Negative Symptom Scale (PANSS) scores compared to the placebo group, reaching the primary endpoint, but peripheral cholinergic side effects remained present (N Engl J Med 2021, 384, 717).

[0011] Positive allosteric modulators (PAMs) of the M1 receptor are one of the hot spots in recent research in the field of mental illness. In a genetic mouse model of schizophrenia, the M1 receptor positive allosteric modulator TAK-071 significantly improved impairments in memory, cognition, sociality, and sensorimotor gating in mice (Neurosci Lett 2021, 764, 136240), and this compound is currently undergoing Phase 2 clinical trials as a treatment for Parkinson's syndrome. Another M1 receptor positive allosteric modulator, MK-7622, ​​is currently undergoing Phase II clinical trials to evaluate its efficacy in treating Alzheimer's disease (ACS Med Chem Lett 2018, 9, 652). In a clinical trial Ib involving schizophrenia patients, Cerevel's M4 receptor positive allosteric modulator CVL-231 significantly reduced patients' total PANSS scores, while common side effects were the same as in the placebo group, and no extrapyramidal side effects were reported. Compared to conventional M receptor orthosteric agonists, positive allosteric modulators may have lower potential risks to the peripheral and central nervous systems, potentially maintaining efficacy while minimizing toxic side effects. Therefore, acting on the allosteric regulatory pocket represents a new direction in treating mental disorders by targeting M receptors. With its excellent drug potential, in vivo efficacy, and safety, M receptor positive allosteric modulators have greater development value and market prospects. [Overview of the project]

[0012] This invention provides nitrogen-containing heterocyclic compounds, pharmaceutically acceptable salts thereof, and methods for preparing and using them. The compounds of this invention can be used as muscarinic receptor positive allosteric modulators. The compounds of this invention can treat diseases mediated by (or associated with) M receptors.

[0013] The present invention provides a compound represented by formula I or a pharmaceutically acceptable salt thereof.

[0014] [ka]

[0015] however,

[0016] [ka]

[0017] teeth,

[0018] [ka]

[0019] And, m is a natural number between 0 and 3. n is a natural number between 0 and 3, and m and n are not both 0 at the same time. k is a natural number between 0 and 3. X1, X2, X3, X4, and X5 are independently -CR 1 -, N, O, S,

[0020] [ka]

[0021] or chemical bond, R N-1 R is hydrogen, C1-C6 alkyl, C1-C6 alkoxy, or 3-7 membered cycloalkyl, where the C1-C6 alkyl and C1-C6 alkoxy are independently 1, 2, 3, or 4 R N-2 Replaced by choice, Each R N-2 It is independently a halogen, Y and Z are independently carbonyl (CO) and -(CR). 2 R 3 ) r- or a chemical bond, r is a natural number from 0 to 5, Each W is independently a carbonyl (CO), -O-, -(CR 4 R 5 )-, -NR 6 - or a chemical bond, Each R 1 is independently hydrogen, halogen, cyano, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, 3-7 member cycloalkyl, 3-7 member heterocycloalkyl or -NR 1-1 R 1-2 , wherein the C1-C6 alkylthio, C1-C6 alkyl and C1-C6 alkoxy are each independently optionally substituted by one, two, three or four R<s a or two R 1 form 3-7 member cycloalkyl or 3-7 member heterocycloalkyl with the atoms to which they are attached, Each R a is independently halogen, cyano, hydroxy, C1-C3 alkyl, C1-C6 alkoxy or -NR 1-4 R 1-5 , or two R a form 3-7 member cycloalkyl or 3-7 member heterocycloalkyl with the atoms to which they are attached, R 1-1 and R 1-2 are independently hydrogen or C1-C6 alkyl, wherein the C1-C6 alkyl is independently optionally substituted by one, two, three or four R b or R 1-1 and R 1-2 form 3-7 member heterocycloalkyl with the atoms to which they are attached, wherein the 3-7 member heterocycloalkyl is independently optionally substituted by one, two, three or four R b-2 , Each R b is independently halogen, cyano, hydroxy, C1-C6 alkoxy, 3-7 member cycloalkyl, 3-7 member heterocycloalkyl, C1-C3 alkyl and NR 1-1-1 R 1-2-1Here, the 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, and C1-C3 alkyl groups are independently one, two, three, or four R groups. b-1 Replaced by choice, Each R b-1 These are independently halogens, hydroxyls, or cyanos. Each R b-2 These are independently halogens, C1-C6 alkyls, or cyanos. R 1-4 and R 1-5 R is independently hydrogen or a C1-C3 alkyl group, where the C1-C3 alkyl group is independently one, two, three, or four R groups. 1-4-1 Replaced by any choice, or R 1-4 and R 1-5 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. R 1-1-1 and R 1-2-1 R is independently hydrogen or a C1-C3 alkyl group, where the C1-C3 alkyl group is independently one, two, three, or four R groups. 1-1-1-1 Replaced by choice, Each R 1-4-1 and R 1-1-1-1 These are independently halogens, hydroxyls, or cyanos. R 2 and R 3 These are independently hydrogen, halogen, cyano, hydroxy, C1-C6 alkoxy or NR 2-1 R 2-2 And, or, R 2 and R 3 These atoms form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them. R 2-1 and R 2-2 R is independently hydrogen or a C1-C6 alkyl group, where the C1-C6 alkyl group is independently one, two, three, or four R groups. d Replaced by any choice, or R 2-1 and R 2-2 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. Each Rd These are independently halogen, cyano, hydroxy, C1-C6 alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, or C1-C3 alkyl. R 4 , R 5 and R 6 These are independently hydrogen, halogen, cyano, hydroxy, C1-C6 alkoxy, C1-C6 alkyl or NR 4-1 R 4-2 Here, the C1-C6 alkyl groups are independently one, two, three, or four R e Replaced by choice, Each R e These are independently halogen, cyano, hydroxy, C1-C3 alkyl, C1-C3 alkoxy, or -NR 4-4 R 4-5 And, R 4-1 and R 4-2 R is independently hydrogen or a C1-C6 alkyl group, where the C1-C6 alkyl group is independently one, two, three, or four R groups. f Replaced by any choice, or R 4-1 and R 4-2 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. Each R f These are independently halogens, cyano, hydroxy, 3-7 membered cycloalkyls, 3-7 membered heterocycloalkyls, C1-C3 alkyls, C1-C3 alkoxys, or -NR 4-1-1 R 4-2-1 And, R 4-4 and R 4-5 R is independently hydrogen or a C1-C3 alkyl group, or 4 and R 5 These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them. R 4-1-1 and R 4-2-1 These are independently hydrogen or C1-C3 alkyl groups. L is

[0022] [ka]

[0023] And, t is a natural number between 0 and 3. u is a natural number between 0 and 3. E is carbonyl,

[0024] [ka]

[0025] , -NHCO-, or a chemical bond, F is carbonyl,

[0026] [ka]

[0027] , -O-, -NH- or chemical bond, R 8 and R 9 R is independently hydrogen, halogen, cyano, hydroxy, or C1-C6 alkyl, where the C1-C6 alkyl is independently one, two, three, or four R g Replaced by any choice, or R 8 and R 9 These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them. Each R g These are independently halogens, cyano, hydroxy, C1-C3 alkyl, or C1-C3 alkoxy. B is a 3-7 member cycloalkyl, a 4-6 member heterocycloalkyl, a 6-10 member aryl, or a 5-12 member heteroaryl, where the 3-7 member cycloalkyl, 4-6 member heterocycloalkyl, 6-10 member aryl, and 5-12 member heteroaryl are independently one, two, or three R i Replaced by choice, Each R iis independently hydrogen, halogen, hydroxy, C1-C3 alkyl, 3-7 member cycloalkyl, 3-7 member heterocycloalkyl, cyano, -NR 11-1 R 11-2 , -OR 11-3 or -SR 11-4 wherein the C1-C3 alkyl is independently optionally substituted by one, two, three or four R i-1 or two R i on the same atom form a 3-7 member cycloalkyl or 3-7 member heterocycloalkyl with the atoms to which they are attached, or two adjacent R i form a 3-7 member cycloalkyl or 3-7 member heterocycloalkyl with the atoms to which they are attached (wherein the 3-7 member cycloalkyl or 3-7 member heterocycloalkyl forms a condensed ring with B), each R i-1 is independently C1-C3 alkyl, halogen, cyano or hydroxy, R 11-1 and R 11-2 are independently hydrogen, C1-C3 alkyl, 3-7 member cycloalkyl or 3-7 member heterocycloalkyl, or R 11-1 and R 11-2 form a 3-7 member cycloalkyl or 3-7 member heterocycloalkyl with the atoms to which they are attached, R 11-3 and R 11-4 are independently C1-C3 alkyl, 3-7 member cycloalkyl or 3-7 member heterocycloalkyl, R 11-1 , R 11-2 , R 11-3 and R 11-4 in which the C1-C3 alkyl, 3-7 member cycloalkyl and 3-7 member heterocycloalkyl are independently optionally substituted by one, two or three R i-2 , each R i-2 is independently C1-C3 alkyl, 3-7 member cycloalkyl, 3-7 member heterocycloalkyl, halogen, cyano or hydroxy, D is hydrogen, halogen, cyano, hydroxy, C1-C6 alkyl, 3-7 member cycloalkyl, 3-7 member heterocycloalkyl, 6-10 member aryl, or 5-12 member heteroaryl, where the C1-C6 alkyl, 3-7 member cycloalkyl, 3-7 member heterocycloalkyl, 6-10 member aryl, and 5-12 member heteroaryl are independently one, two, or three R j Replaced by choice, Each R j These are independently hydrogen, halogen, cyano, hydroxy, C1-C3 alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, and -NR. 12-1 R 12-2 , -OR 12-3 or -SR 12-4 The C1-C3 alkyl, 3-7 membered cycloalkyl, and 3-7 membered heterocycloalkyl groups are independently one, two, or three R groups. k Replaced by choice, R 12-1 , R 12-2 , R 12-3 and R 12-4 R is independently hydrogen, a C1-C3 alkyl, a 3-7 membered cycloalkyl, or a 3-7 membered heterocycloalkyl, where the C1-C3 alkyl, 3-7 membered cycloalkyl, and 3-7 membered heterocycloalkyl are independently one, two, or three R k-1 Replaced by any choice, or R 12-1 and R 12-2 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. Each R k These are independently halogen, cyano, hydroxy, C1-C3 alkyl, 3-7 membered cycloalkyl, or 3-7 membered heterocycloalkyl. Each R k-1 These are independently halogen, cyano, hydroxy, C1-C3 alkyl, 3-7 membered cycloalkyl, or 3-7 membered heterocycloalkyl. A

[0028] [ka]

[0029] And X1, X2 and X3 are CR 1 If this is the case, the compound represented by formula I satisfies one of the following conditions.

[0030] (1) E is -NHCO- or a chemical bond, and F is -O-, -NH- or a chemical bond. (2) The condition is that E is a carbonyl group and F is a -NH- group. (3) L is -(CH2)-, -(CH2)2-,

[0031] [ka]

[0032] The condition, (4) If E or F is a carbonyl, B is a 4-7 membered cycloalkyl, a 6-10 membered aryl, a 5-12 membered heteroaryl, or one, two, or three R i A 4-6 member heterocycloalkyl substituted with R, where R is located on two identical atoms. i These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, or two adjacent R i These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them (where the 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl forms a fused ring with B), where the 4-7 membered cycloalkyl, 6-10 membered aryl, and 5-12 membered heteroaryl independently form one, two, or three R i Conditions that are optionally replaced by, (5)

[0033] [ka]

[0034] teeth,

[0035] [ka]

[0036] And, A

[0037] [ka]

[0038] In this case, the number of heteroatoms in X1, X2, and X4 is one or two. A

[0039] [ka]

[0040] And if L is a carbonyl group, then u is a natural number from 1 to 3, B is a 4-6 member heterocycloalkyl group, and the 4-6 member heterocycloalkyl group independently has one, two or three R groups. i Replaced by choice, In the aforementioned 3- to 7-membered heterocycloalkyl, 4- to 6-membered heterocycloalkyl, and 5- to 12-membered heteroaryl, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 5.

[0041] In one embodiment, some groups in the compound represented by formula I or a pharmaceutically acceptable salt thereof have the following definitions, and the definitions of groups not mentioned are as described in any one embodiment of the present invention (hereinafter, the contents of this paragraph are referred to as “in one embodiment,” “in several embodiments,” “in one form,” or “in one preferred embodiment.”).

[0042] In one embodiment,

[0043] [ka]

[0044] And, Here,

[0045] [ka]

[0046] teeth,

[0047] [ka]

[0048] And, m is a natural number between 0 and 3. n is a natural number between 0 and 3, and m and n are not both 0 at the same time. k is a natural number between 0 and 3. X1, X2, X3, X4, and X5 are independently -CR 1 -, N, O, S,

[0049] [ka]

[0050] or chemical bond, R N-1 R is hydrogen or a C1-C6 alkyl, C1-C6 alkoxy, or 3-7 membered cycloalkyl, where the C1-C6 alkyl and C1-C6 alkoxy are independently 1, 2, 3, or 4 R N-2 Replaced by choice, Each R N-2 It is independently a halogen, Y and Z are independently carbonyl (CO) and -(CR). 2 R 3 ) r -or a chemical bond, where r is a natural number between 0 and 5. Each W is independently carbonyl (CO), -O-, and -(CR). 4 R 5 )-, -NR6 -or chemical bond, Each R 1 These are independently hydrogen, halogen, cyano, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, or -NR 1-1 R 1-2 Here, the C1-C6 alkyl and C1-C6 alkoxy are independently one, two, three, or four R a It is optionally replaced by, or two R 1 These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them. Each R a These are independently halogen, cyano, hydroxy, C1-C3 alkyl, C1-C6 alkoxy, or -NR 1-4 R 1-5 And, or, two R's a These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, R 1-1 and R 1-2 R is independently hydrogen or a C1-C6 alkyl group, where the C1-C6 alkyl group is independently one, two, three, or four R groups. b Replaced by any choice, or R 1-1 and R 1-2 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. Each R b These are independently halogens, cyano, hydroxy, C1-C6 alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, C1-C3 alkyl, and NR 1-1-1 R 1-2-1 Here, the 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, and C1-C3 alkyl groups are independently one, two, three, or four R groups. b-1 Replaced by choice, Each R b-1 These are independently halogens, hydroxyls, or cyanos. R 1-4 and R 1-5R is independently hydrogen or a C1-C3 alkyl group, where the C1-C3 alkyl group is independently one, two, three, or four R groups. 1-4-1 Replaced by any choice, or R 1-4 and R 1-5 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. R 1-1-1 and R 1-2-1 R is independently hydrogen or a C1-C3 alkyl group, where the C1-C3 alkyl group is independently one, two, three, or four R groups. 1-1-1-1 Replaced by choice, Each R 1-4-1 and R 1-1-1-1 These are independently halogens, hydroxyls, or cyanos. R 2 and R 3 These are independently hydrogen, halogen, cyano, hydroxy, C1-C6 alkoxy or NR 2-1 R 2-2 And, or, R 2 and R 3 These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them. R 2-1 and R 2-2 R is independently hydrogen or a C1-C6 alkyl group, where the C1-C6 alkyl group is independently one, two, three, or four R groups. d Replaced by any choice, or R 2-1 and R 2-2 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. Each R d These are independently halogen, cyano, hydroxy, C1-C6 alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, or C1-C3 alkyl. R 4 , R 5 and R 6 These are independently hydrogen, halogen, cyano, hydroxy, C1-C6 alkoxy, C1-C6 alkyl or NR 4-1 R 4-2Here, the C1-C6 alkyl groups are independently one, two, three, or four R e Replaced by choice, Each R e These are independently halogen, cyano, hydroxy, C1-C3 alkyl, C1-C3 alkoxy, or -NR 4-4 R 4-5 And, R 4-1 and R 4-2 R is independently hydrogen or a C1-C6 alkyl group, where the C1-C6 alkyl group is independently one, two, three, or four R groups. f Replaced by any choice, or R 4-1 and R 4-2 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. Each R f These are independently halogens, cyano, hydroxy, 3-7 membered cycloalkyls, 3-7 membered heterocycloalkyls, C1-C3 alkyls, C1-C3 alkoxys, or -NR 4-1-1 R 4-2-1 And, R 4-4 and R 4-5 R is independently hydrogen or a C1-C3 alkyl group, or 4 and R 5 These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them. R 4-1-1 and R 4-2-1 These are independently hydrogen or C1-C3 alkyl groups. L is

[0051] [ka]

[0052] And, t is a natural number between 0 and 3. u is a natural number between 0 and 3. E is a carbonyl, -NHCO-, or chemical bond. F is a carbonyl, -O-, -NH-, or chemical bond. R 8 and R 9 R is independently hydrogen, halogen, cyano, hydroxy, or C1-C6 alkyl, where the C1-C6 alkyl is independently one, two, three, or four R g Replaced by any choice, or R 8 and R 9 These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them. Each R g These are independently halogens, cyano, hydroxy, C1-C3 alkyl, or C1-C3 alkoxy. B is a 3-7 member cycloalkyl, a 4-6 member heterocycloalkyl, a 6-10 member aryl, or a 5-12 member heteroaryl, where the 3-7 member cycloalkyl, 4-6 member heterocycloalkyl, 6-10 member aryl, and 5-12 member heteroaryl are independently one, two, or three R i Replaced by choice, Each R i These are independently hydrogen, halogen, hydroxyl, C1-C3 alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, cyano, and -NR. 11-1 R 11-2 , -OR 11-3 or -SR 11-4 Here, the C1-C3 alkyl groups are independently one, two, three, or four R i-1 It is optionally replaced by, or R on two identical atoms. i These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, or two adjacent R i These atoms form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them (where the 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups form a fused ring with B), Each R i-1 These are independently C1-C3 alkyl, halogen, cyano, or hydroxy, R 11-1 and R 11-2R is independently hydrogen, C1-C3 alkyl, 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl, or R 11-1 and R 11-2 These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them. R 11-3 and R 11-4 These are independently C1-C3 alkyl, 3-7 membered cycloalkyl, or 3-7 membered heterocycloalkyl. R 11-1 , R 11-2 , R 11-3 and R 11-4 In this, the C1-C3 alkyl, 3-7 membered cycloalkyl, and 3-7 membered heterocycloalkyl groups are independently one, two, or three R groups. i-2 Replaced by choice, Each R i-2 These are independently C1-C3 alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, halogen, cyano, or hydroxy. D is hydrogen, halogen, cyano, hydroxy, C1-C6 alkyl, 3-7 member cycloalkyl, 3-7 member heterocycloalkyl, 6-10 member aryl, or 5-12 member heteroaryl, where the C1-C6 alkyl, 3-7 member cycloalkyl, 3-7 member heterocycloalkyl, 6-10 member aryl, and 5-12 member heteroaryl are independently one, two, or three R j Replaced by choice, Each R j These are independently hydrogen, halogen, cyano, hydroxy, C1-C3 alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, and -NR. 12-1 R 12-2 , -OR 12-3 or -SR 12-4 The C1-C3 alkyl, 3-7 membered cycloalkyl, and 3-7 membered heterocycloalkyl groups are independently one, two, or three R groups. k Replaced by choice, R 12-1 , R 12-2 , R 12-3 and R 12-4R is independently hydrogen, a C1-C3 alkyl, a 3-7 membered cycloalkyl, or a 3-7 membered heterocycloalkyl, where the C1-C3 alkyl, 3-7 membered cycloalkyl, and 3-7 membered heterocycloalkyl are independently one, two, or three R k-1 Replaced by any choice, or R 12-1 and R 12-2 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. Each R k These are independently halogen, cyano, hydroxy, C1-C3 alkyl, 3-7 membered cycloalkyl, or 3-7 membered heterocycloalkyl. Each R k-1 These are independently halogen, cyano, hydroxy, C1-C3 alkyl, 3-7 membered cycloalkyl, or 3-7 membered heterocycloalkyl. A

[0053] [ka]

[0054] And X1, X2 and X3 are CR 1 If this is the case, the compound represented by formula I satisfies one of the following conditions.

[0055] (1) E is -NHCO- or a chemical bond, and F is -O-, -NH- or a chemical bond. (2) The condition is that E is a carbonyl group and F is a -NH- group. (3) L is -(CH2)-, -(CH2)2-,

[0056] [ka]

[0057] The condition, (4) If E or F is a carbonyl, B is a 4-7 membered cycloalkyl, a 6-10 membered aryl, a 5-12 membered heteroaryl, or one, two, or three R iA 4-6 member heterocycloalkyl substituted with R, where R is located on two identical atoms. i These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, or two adjacent R i These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them (where the 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl forms a fused ring with B), where the 4-7 membered cycloalkyl, 6-10 membered aryl, and 5-12 membered heteroaryl independently form one, two, or three R i Conditions that are optionally replaced by, (5)

[0058] [ka]

[0059] teeth,

[0060] [ka]

[0061] And, A

[0062] [ka]

[0063] In this case, the number of heteroatoms in X1, X2, and X4 is one or two. A

[0064] [ka]

[0065] And if L is a carbonyl group, then u is a natural number between 1 and 3, B is a 4-6 member heterocycloalkyl group, and the 4-6 member heterocycloalkyl group independently has one, two or three R groups. i Replaced by choice, In the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl, the heteroatoms are N, O, or S, and the number of heteroatoms is 1 to 5, or in the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 5.

[0066] In one embodiment, m is preferably a natural number between 0 and 3, for example, 0, 1, 2, or 3, and also, for example, 1, 2, or 3.

[0067] In one embodiment, n is preferably a natural number between 1 and 3, for example, 1, 2, or 3, and also, for example, 1 or 2.

[0068] In one embodiment, n is 1.

[0069] In one embodiment, X1 is N, and X2, X3 and X4 are -CR 1 -If Y and Z are independently -(CH2)-, m and n are 2, R j It is trifluoromethyl.

[0070] In one embodiment,

[0071] [ka]

[0072] teeth,

[0073] [ka]

[0074] That is the case.

[0075] In one embodiment,

[0076] [ka]

[0077] teeth,

[0078] [ka]

[0079] That is the case.

[0080] In one embodiment, m is 1.

[0081] In one embodiment, k is preferably a natural number between 0 and 3, for example, 0, 1, 2, or 3, and also, for example, 1, 2, or 3.

[0082] In one embodiment, r is preferably a natural number between 0 and 5, for example, 0, 1, 2, 3, 4, or 5, and also, for example, 1 or 2.

[0083] In one embodiment, r is 1.

[0084] In one embodiment, r is a natural number between 0 and 3, for example, 1 or 2.

[0085] In one embodiment, R N-1 These are C1-C6 alkyl groups.

[0086] In one embodiment, R N-1 These are hydrogen, a C1-C6 alkyl group, or a 3-7 membered cycloalkyl group.

[0087] In one embodiment, each W is independently -(CR 4 R 5 )-, -O-, -NR 6 -or it is a chemical bond.

[0088] In one embodiment, each W is independently -(CR 4 R 5 )-, -NR 6 -or it is a chemical bond.

[0089] In one embodiment, Y and Z are independently carbonyl (CO) or -(CR). 2 R 3 ) r - is

[0090] In one embodiment, Y and Z are independently -(CR 2 R 3 ) r - is

[0091] In one embodiment, each R 1 These are independently hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, or -NR 1-1 R 1-2 That is the case.

[0092] In one embodiment, each R 1 These are independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, or -NR 1-1 R 1-2 That is the case.

[0093] In one embodiment, each R 1 These are independently hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, or -NR 1-1 R 1-2 For example, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio or -NR1-1 R 1-2 That is the case.

[0094] In one embodiment, each R 1 These are independently hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, or -NR 1-1 R 1-2 Here, the C1-C6 alkylthio, C1-C6 alkyl, and C1-C6 alkoxy are independently one, two, three, or four R a It is replaced by an optional choice.

[0095] In one embodiment, each R 1 These are independently hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, or -NR 1-1 R 1-2 That is the case.

[0096] In one embodiment, each R 1 These are independently C1-C6 alkyl groups.

[0097] In one embodiment, each R 1 These are independently C1-C6 alkyl or C1-C6 alkoxy.

[0098] In one embodiment, R 1-1 and R 1-2 R is independently hydrogen or a C1-C6 alkyl group, or 1-1 and R 1-2 These form 3-7 member heterocycloalkyl groups with the atoms linked to them, for example, R 1-1 and R 1-2 These atoms form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them.

[0099] In one embodiment, X1 and X3 are independently N, and X4 and X2 are independently -CR 1 -If each R 1These are independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, 3-7 member heterocycloalkyl, or -NR 1-1 R 1-2 That is the case.

[0100] In one embodiment, X2 independently becomes -CR 1 -If R 1 (In X2) is a C1-C6 alkyl or C1-C6 alkoxy.

[0101] In one embodiment, if D is pyrimidinyl, then each R 1 These are independently halogens or 3- to 7-membered cycloalkyl groups.

[0102] In one embodiment, X2 and X3 are independently N, and X4 and X1 are independently -CR 1 -If each R 1 These are independently C1-C6 alkyl or 3-7 membered heterocycloalkyl groups.

[0103] In one embodiment, each R a These are independently hydroxy, C1-C3 alkoxy, or NR 1-4 R 1-5 That is the case.

[0104] In one embodiment, each R a These are independently halogens, hydroxyls, C1-C6 alkoxys, or -NRs. 1-4 R 1-5 For example, each R a These are independently hydroxy, C1-C6 alkoxy, or -NR 1-4 R 1-5 And also, for example, hydroxyl.

[0105] In one embodiment, each R b These are independently hydroxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, C1-C3 alkyl, C1-C3 alkoxy, or NR 1-1-1 R 1-2-1 That is the case.

[0106] In one embodiment, each R b These are independently hydroxy, 3-7 membered cycloalkyl, or C1-C3 alkyl, for example, each R b These are independently hydroxy, 3- to 7-membered cycloalkyl groups.

[0107] In one embodiment, each R b These are independently 3- to 7-membered cycloalkyl groups.

[0108] In one embodiment, R b-1 It is independently hydroxyl.

[0109] In one embodiment, each R b-1 It is independently hydroxyl.

[0110] In one embodiment, each R b-2 These are independently halogens and C1-C6 alkyl groups.

[0111] In one embodiment, R 1-4 and R 1-5 These are independently C1-C3 alkyl groups.

[0112] In one embodiment, each R 1-4-1 These are halogens, independently.

[0113] In one embodiment, R 1-4-1 It is a halogen.

[0114] In one embodiment, R 2 and R 3 It is independently hydrogen or NR 2-1 R 2-2 That is the case.

[0115] In one embodiment, R 2 and R 3 It is hydrogen independently.

[0116] In one embodiment, R 2-1 and R 2-2 This is independently hydrogen or a C1-C6 alkyl group, for example, hydrogen.

[0117] In one embodiment, R 4 , R 5 and R 6 It is hydrogen independently.

[0118] In one embodiment, R 4 , R 5 and R 6 It is independently hydrogen or NR 4-1 R 4-2 That is the case.

[0119] In one embodiment, R 4-1 and R 4-2 It is hydrogen independently.

[0120] In one embodiment, R e -NR 4-4 R 4-5 That is the case.

[0121] In one embodiment, R 4-4 and R 4-5 These are independently hydrogen or C1-C3 alkyl groups.

[0122] In one embodiment, E is a carbonyl,

[0123] [ka]

[0124] It is -NHCO- or a chemical bond.

[0125] In one embodiment, E is a carbonyl or chemical bond.

[0126] In one embodiment, E is a carbonyl group.

[0127] In one embodiment, t is 0.

[0128] In one embodiment, F is -NH-, -O-, or a chemical bond.

[0129] In one embodiment, F is a carbonyl,

[0130] [ka]

[0131] It is -O-, -NH-, or a chemical bond.

[0132] In one embodiment, F is a chemical bond.

[0133] In one embodiment, R 8 and R 9 R is independently hydrogen or a C1-C6 alkyl group, or 8 and R 9 These atoms form 3- to 7-membered cycloalkyl or 3- to 7-membered heterocycloalkyl groups with the atoms linked to them.

[0134] In one embodiment, R 8 and R 9 R is independently hydrogen or a C1-C6 alkyl group, or 8 and R 9 These atoms form 3- to 7-membered cycloalkyl groups with the atoms linked to them.

[0135] In one embodiment, R 8 and R 9 These are independently C1-C6 alkyl groups, or R 8 and R 9 These atoms form 3- to 7-membered cycloalkyl or 3- to 7-membered heterocycloalkyl groups with the atoms linked to them.

[0136] In one embodiment, B is a 4-6 member heterocycloalkyl, a 6-10 member aryl, or a 5-12 member heteroaryl, where the 5-12 member heteroaryl, 6-10 member aryl, and 4-6 member heterocycloalkyl are independently one, two, or three R i It is replaced by an optional choice.

[0137] In one embodiment, B is a 4-6 member heterocycloalkyl or a 5-12 member heteroaryl, where the 5-12 member heteroaryl and the 4-6 member heterocycloalkyl are independently one, two or three R i It is replaced by an optional choice.

[0138] In one embodiment, B is a 4-6 member heterocycloalkyl, where the 4-6 member heterocycloalkyl is independently one, two, or three R i Replaced by choice, In one embodiment, if B is a 6-10 member aryl or 5-12 member heteroaryl, then D is hydrogen, halogen, cyano, hydroxy, C1-C6 alkyl, 3-7 member cycloalkyl, or 3-7 member heterocycloalkyl, where the C1-C6 alkyl, 3-7 member cycloalkyl, or 3-7 member heterocycloalkyl independently comprises one, two, or three R j It is optionally substituted by, and preferably, D is hydrogen or a C1-C6 alkyl group.

[0139] In one embodiment, X2 and X3 are independently N, and X4 and X1 are independently -CR 1 -If B is azetidinil (for example,

[0140] [ka]

[0141] )

[0142] In one embodiment, X1 and X3 (or X2 and X4) are -CR 1 - and R 1 If the alkyl group is C1-C6, then each R j These are independently -OR 12-3 or -SR 12-4 That is the case.

[0143] In one embodiment, R i is hydrogen, halogen, hydroxyl, or C1-C3 alkyl, or two R i These atoms form 3- to 7-membered cycloalkyl or 3- to 7-membered heterocycloalkyl groups with the atoms linked to them.

[0144] In one embodiment, each R i These are independently hydrogen, halogen, hydroxyl, or C1-C3 alkyl, or two R i These form 3- to 7-membered cycloalkyl groups with the atoms linked to them, for example, R i is hydrogen or a C1-C3 alkyl group, for example, a C1-C3 alkyl group. In one embodiment, R i It is hydrogen.

[0145] In one embodiment, D is hydrogen, a C1-C6 alkyl or a 5-12 member heteroaryl, where the C1-C6 alkyl and 5-12 member heteroaryl are independently one, two or three R j It is replaced by an optional choice.

[0146] In one embodiment, D is hydrogen, a 3- to 7-membered cycloalkyl, a C1- to C6 alkyl, or a 5- to 6-membered heteroaryl, where the C1- to C6 alkyl and the 5- to 6-membered heteroaryl are independently one, two, or three R j It is replaced by an optional choice.

[0147] In one embodiment, D is a 5- to 12-membered heteroaryl, where the 5- to 12-membered heteroaryl is independently one, two, or three R jIt is replaced by an optional choice.

[0148] In one embodiment, D is a 5-6 member heteroaryl, where the 5-6 member heteroaryl is independently one, two, or three R j It is replaced by an optional choice.

[0149] In one embodiment, X2 and X3 are independently N, and X4 and X1 are independently -CR 1 -If D is a 6-membered heteroaryl (for example,

[0150] [ka]

[0151] ) where the 6-membered heteroaryl is independently one, two or three R j It is replaced by an optional choice.

[0152] In one embodiment, if D is a 5-membered heteroaryl, then the 5-membered heteroaryl is

[0153] [ka]

[0154] And each R 1 These are independently C1-C6 alkyl or C1-C6 alkoxy.

[0155] In one embodiment, R j These are halogens, C1-C3 alkyls, OR 12-3 or SR 12-4 That is the case.

[0156] In one embodiment, each R j These are independently C1-C3 alkyl, OR 12-3 or SR 12-4 The C1-C3 alkyl groups are independently one, two, or three R groups.k They are optionally replaced by each R j OR 12-3 or SR 12-4 That is the case.

[0157] In one embodiment, each R j These are independently halogens, C1-C3 alkyls, and OR 12-3 or SR 12-4 That is the case.

[0158] In one embodiment, each R j These are independently hydrogen, halogen, C1-C3 alkyl, 3-7 membered cycloalkyl, and -OR 12-3 or -SR 12-4 That is the case.

[0159] In one embodiment, each R j These are independently hydrogen, halogen, C1-C3 alkyl, 3-7 membered cycloalkyl, and -OR 12-3 or -SR 12-4 The C1-C3 alkyl and 3-7 membered cycloalkyl groups are independently one, two, or three R groups. k It is replaced by an optional choice.

[0160] In one embodiment, R j is OR 12-3 That is the case.

[0161] In one embodiment, each R j OR 12-3 That is the case.

[0162] In one embodiment, R j These are halogens or C1-C3 alkyl groups.

[0163] In one embodiment, each R j These are independently halogens or C1-C3 alkyl groups.

[0164] In one embodiment, X1 and X3 are independently N, and X4 and X2 are independently -CR 1 - and each R 1 If R is independently a C1-C6 alkyl and a C1-C6 alkoxy, then each R j These are independently halogens, 3-7 membered cycloalkyls, OCH2CF3,

[0165] [ka]

[0166] or SR 12-4 That is the case.

[0167] In one embodiment,

[0168] [ka]

[0169] but

[0170] [ka]

[0171] If so, each R j OR 12-3 or SR 12-4 That is the case.

[0172] In one embodiment, X1 or X4 is -CR 1 - and R 1 These are independently 3-7 member heterocycloalkyl or -NR 1-1 R 1-2 If so, each R j OR 12-3 or SR 12-4 That is the case.

[0173] In one embodiment, R 12-3 and R 12-4These are independently C1-C3 alkyl groups.

[0174] In one embodiment, R 12-3 and R 12-4 These are independently C1-C3 alkyl groups, where the C1-C3 alkyl group independently has one, two, or three R groups. k-1 It is replaced by an optional choice.

[0175] In one embodiment, R 12-1 , R 12-2 , R 12-3 and R 12-4 These are independently C1-C3 alkyl groups.

[0176] In one embodiment, each R k These are halogens, independently.

[0177] In one embodiment, R k These are halogens, independently.

[0178] In one embodiment, each R k-1 These are halogens, independently.

[0179] In one embodiment, R k-1 These are halogens, independently.

[0180] In one embodiment, the heteroatoms in the 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl are N, O, or S, and the number of heteroatoms is 1 to 3.

[0181] In one embodiment, the heteroatoms in the 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl are N, O, or S, and the number of heteroatoms is 1 to 5.

[0182] In one embodiment, the heteroatoms in the 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, 5-6 member heteroaryl, and 5-12 member heteroaryl are N, O, or S, and the number of heteroatoms is 1 to 3.

[0183] In one embodiment, the heteroatoms in the 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, 5-6 member heteroaryl, and 5-12 member heteroaryl are selected from one, two, or three of N, O, or S, and the number of heteroatoms is one, two, or three.

[0184] In one embodiment, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, where the heteroatoms are, for example, one or two of N and O, and the number of heteroatoms is, for example, one or two.

[0185] In one embodiment, the 4- to 6-membered heterocycloalkyl is a 4-membered heterocycloalkyl, where the heteroatoms are, for example, one or two of N and O, and the number of heteroatoms is, for example, one.

[0186] In one embodiment, the 5-6 membered heteroaryl is a 6-membered heteroaryl, where the heteroatoms are, for example, one or two of N and O, and the number of heteroatoms is, for example, one.

[0187] In one embodiment, the 5-12 membered heteroaryl is a 5-10 membered heterocycloalkyl, where the heteroatoms are, for example, one or two of N and O, and the number of heteroatoms is, for example, one.

[0188] In one embodiment, A

[0189] [ka]

[0190] And X1, X2 and X3 are CR 1 If so, then E or F in the compound represented by formula I is

[0191] [ka]

[0192] And, In one embodiment, R N-1 The C1-C6 alkyl group in is preferably a C1-C3 alkyl group, such as methyl, ethyl, n-propyl, or isopropyl.

[0193] In one embodiment, R N-1 The C1-C6 alkoxy in the above is preferably a C1-C3 alkoxy, such as methoxy, ethoxy, n-propoxy, or isopropoxy.

[0194] In one embodiment, R N-1 The 3- to 7-membered cycloalkyl group in the above is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl.

[0195] In one embodiment, R N-2 The halogen in is F, Cl, Br, or I, for example, F or Cl.

[0196] In one embodiment, R 1 The halogen in is F, Cl, Br, or I, for example, F or Cl, and also for example, Cl.

[0197] In one embodiment, R 1 The C1-C6 alkyl group in is preferably a C1-C3 alkyl group, such as methyl, ethyl, n-propyl, or isopropyl.

[0198] In one embodiment, R 1 The C1-C6 alkoxy in is preferably a C1-C3 alkoxy, such as methoxy, ethoxy, n-propoxy, or isopropoxy, or, for example, methoxy or ethoxy.

[0199] In one embodiment, R 1 The C1-C6 alkylthio in is preferably a C1-C3 alkylthio, such as methylthio, ethylthio, n-propylthio, or isopropylthio, and also, for example, methylthio.

[0200] In one embodiment, R 1 The 3- to 7-membered cycloalkyl group in the above is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl, or, for example, cyclopropyl or cyclobutyl.

[0201] In one embodiment, R 1 The 3-7 member heterocycloalkyl in is preferably a 3-6 member heterocycloalkyl, the heteroatom in the 3-6 member heterocycloalkyl is preferably N or O, the number of heteroatoms in the 3-6 member heterocycloalkyl is preferably 1 or 2, and the 3-6 member heterocycloalkyl is more preferably a 4 member heterocycloalkyl, for example,

[0202] [ka]

[0203] That is the case.

[0204] In one embodiment, R 1The 3-7 member heterocycloalkyl in is preferably a 3-6 member heterocycloalkyl, the heteroatom in the 3-6 member heterocycloalkyl is preferably N or O, the number of heteroatoms in the 3-6 member heterocycloalkyl is preferably 1 or 2, and the 3-6 member heterocycloalkyl is more preferably a 4 member heterocycloalkyl, for example,

[0205] [ka]

[0206] That is the case.

[0207] In one embodiment, R a The halogen in is preferably F, Cl, Br, or I, for example, F or Cl, and also for example, F.

[0208] In one embodiment, R a The C1-C3 alkyl group in the above is preferably methyl, ethyl, n-propyl, or isopropyl.

[0209] In one embodiment, R a The C1-C6 alkoxy in is preferably a C1-C3 alkoxy, such as methoxy, ethoxy, n-propoxy, or isopropoxy, and also, for example, methoxy.

[0210] In one embodiment, R a The 3-7 member heterocycloalkyl in is preferably a 3-6 member heterocycloalkyl, the heteroatom in the 3-6 member heterocycloalkyl is preferably N or O, the number of heteroatoms in the 3-6 member heterocycloalkyl is preferably 1 or 2, and the 3-6 member heterocycloalkyl is more preferably a 4 member heterocycloalkyl, for example,

[0211] [ka]

[0212] That is the case.

[0213] In one embodiment, R a The 3- to 7-membered cycloalkyl group in the above is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl.

[0214] In one embodiment, R 1-1 and R 1-2 The C1-C6 alkyl group in is preferably a C1-C3 alkyl group, such as methyl, ethyl, n-propyl, or isopropyl, and also, for example, methyl or ethyl (for example, methyl).

[0215] In one embodiment, R 1-1 and R 1-2 The 3-7 member heterocycloalkyl in is preferably a 3-6 member heterocycloalkyl, the heteroatom in the 3-6 member heterocycloalkyl is preferably N or O, the number of heteroatoms in the 3-6 member heterocycloalkyl is preferably one or two, the 3-6 member heterocycloalkyl is, for example, a 4 member heterocycloalkyl, and also, for example,

[0216] [ka]

[0217] That is the case.

[0218] In one embodiment, R b The halogen in is preferably F, Cl, Br, or I, for example, F or Cl.

[0219] In one embodiment, R bThe C1-C6 alkoxy in the above is preferably a C1-C3 alkoxy, such as methoxy, ethoxy, n-propoxy, or isopropoxy.

[0220] In one embodiment, R b The 3- to 7-membered cycloalkyl group in the above is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl, and also, for example, cyclopropyl.

[0221] In one embodiment, R b The 3- to 7-membered heterocycloalkyl group is preferably a 3- to 6-membered heterocycloalkyl group, the heteroatom in the 3- to 6-membered heterocycloalkyl group is preferably N or O, and the number of heteroatoms in the 3- to 6-membered heterocycloalkyl group is preferably one or two.

[0222] In one embodiment, R b The C1-C3 alkyl group in the above is preferably methyl, ethyl, n-propyl, or isopropyl, for example, methyl.

[0223] In one embodiment, R b-1 The halogen in is preferably F, Cl, Br, or I, for example, F or Cl.

[0224] In one embodiment, R b-2 The halogen in is preferably F, Cl, Br, or I, for example, F.

[0225] In one embodiment, R b-2 The C1-C6 alkyl group in is preferably a C1-C3 alkyl group, for example, methyl, ethyl, n-propyl, or isopropyl, and also, for example, methyl (for example,

[0226] [ka]

[0227] )

[0228] In one embodiment, R 1-4 and R 1-5 The C1-C3 alkyl group in is preferably methyl, ethyl, n-propyl, or isopropyl, for example, methyl, ethyl, or n-propyl, and also, for example, methyl.

[0229] In one embodiment, R 1-4 and R 1-5 The 3-7 member heterocycloalkyl in is preferably a 3-6 member heterocycloalkyl, the heteroatom in the 3-6 member heterocycloalkyl is preferably N or O, the number of heteroatoms in the 3-6 member heterocycloalkyl is preferably 1 or 2, and the 3-6 member heterocycloalkyl is more preferably a 4 member heterocycloalkyl, for example,

[0230] [ka]

[0231] That is the case.

[0232] In one embodiment, R 1-1-1 and R 1-2-1 The C1-C3 alkyl group in the above is preferably methyl, ethyl, n-propyl, or isopropyl.

[0233] In one embodiment, R 1-4-1 and R 1-1-1-1 The halogen in is preferably F, Cl, Br, or I, for example, F or Cl, and also for example, F.

[0234] In one embodiment, R 2 and R 3The halogen in is preferably F, Cl, Br, or I, for example, F or Cl.

[0235] In one embodiment, R 2 and R 3 The C1-C6 alkoxy in the above is preferably a C1-C3 alkoxy, such as methoxy, ethoxy, n-propoxy, or isopropoxy.

[0236] In one embodiment, R 2 and R 3 The 3- to 7-membered cycloalkyl group in the above is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl.

[0237] In one embodiment, R 2 and R 3 The 3- to 7-membered heterocycloalkyl group is preferably a 3- to 6-membered heterocycloalkyl group, the heteroatom in the 3- to 6-membered heterocycloalkyl group is preferably N or O, and the number of heteroatoms in the 3- to 6-membered heterocycloalkyl group is preferably one or two.

[0238] In one embodiment, R 2-1 and R 2-2 The C1-C6 alkyl group in is preferably a C1-C3 alkyl group, such as methyl, ethyl, n-propyl, or isopropyl, and also, for example, methyl or ethyl.

[0239] In one embodiment, R 2-1 and R 2-2 The 3- to 7-membered heterocycloalkyl group is preferably a 3- to 6-membered heterocycloalkyl group, the heteroatom in the 3- to 6-membered heterocycloalkyl group is preferably N or O, and the number of heteroatoms in the 3- to 6-membered heterocycloalkyl group is preferably one or two.

[0240] In one embodiment, R d The halogen in is preferably F, Cl, Br, or I, for example, F or Cl.

[0241] In one embodiment, R d The C1-C6 alkoxy in the above is preferably a C1-C3 alkoxy, such as methoxy, ethoxy, n-propoxy, or isopropoxy.

[0242] In one embodiment, R d The 3- to 7-membered cycloalkyl group in the above is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl.

[0243] In one embodiment, R d The 3- to 7-membered heterocycloalkyl group is preferably a 3- to 6-membered heterocycloalkyl group, the heteroatom of the 3- to 7-membered heterocycloalkyl group is preferably N or O, and the number of heteroatoms of the 3- to 6-membered heterocycloalkyl group is preferably one or two.

[0244] In one embodiment, R d The C1-C3 alkyl group in the above is preferably methyl, ethyl, n-propyl, or isopropyl.

[0245] In one embodiment, R 4 , R 5 and R 6 The halogen in is preferably F, Cl, Br, or I, for example, F or Cl.

[0246] In one embodiment, R 4 , R 5 and R 6 The C1-C6 alkoxy in the above is preferably a C1-C3 alkoxy, such as methoxy, ethoxy, n-propoxy, or isopropoxy.

[0247] In one embodiment, R 4 , R 5 and R 6 The C1-C6 alkyl group in the above is preferably a C1-C3 alkyl group, such as methyl, ethyl, n-propyl, or isopropyl.

[0248] In one embodiment, R e The halogen in is preferably F, Cl, Br, or I, for example, F or Cl.

[0249] In one embodiment, R e The C1-C3 alkyl group in the above is preferably methyl, ethyl, n-propyl, or isopropyl.

[0250] In one embodiment, R e The C1-C3 alkoxys in the above are preferably methoxy, ethoxy, n-propoxy, or isopropoxy.

[0251] In one embodiment, R 4-1 and R 4-2 The C1-C6 alkyl group in the above is preferably a C1-C3 alkyl group, such as methyl, ethyl, n-propyl, or isopropyl.

[0252] In one embodiment, R 4-1 and R 4-2 The 3- to 7-membered heterocycloalkyl group is preferably a 3- to 6-membered heterocycloalkyl group, the heteroatom in the 3- to 6-membered heterocycloalkyl group is preferably N or O, and the number of heteroatoms in the 3- to 6-membered heterocycloalkyl group is preferably one or two.

[0253] In one embodiment, R f The halogen in is preferably F, Cl, Br, or I, for example, F or Cl.

[0254] In one embodiment, R f The 3- to 7-membered cycloalkyl group in the above is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclopropyl, or cyclopentyl.

[0255] In one embodiment, R f The 3- to 7-membered heterocycloalkyl group is preferably a 3- to 6-membered heterocycloalkyl group, the heteroatom in the 3- to 6-membered heterocycloalkyl group is preferably N or O, and the number of heteroatoms in the 3- to 6-membered heterocycloalkyl group is preferably one or two.

[0256] In one embodiment, R f The C1-C3 alkyl group in the above is preferably methyl, ethyl, n-propyl, or isopropyl.

[0257] In one embodiment, R f The C1-C3 alkoxys in the above are preferably methoxy, ethoxy, n-propoxy, or isopropoxy.

[0258] In one embodiment, R 4-4 and R 4-5 The C1-C3 alkyl group in the above is preferably methyl, ethyl, n-propyl, or isopropyl.

[0259] In one embodiment, t is a natural number between 0 and 3, for example 0, 1, 2, or 3, and further, for example 0, 1, or 2, and for example 0.

[0260] In one embodiment, u is a natural number between 0 and 3, for example, 0, 1, 2, or 3, and further, for example, 0, 1, or 2, and for example, 1.

[0261] In one embodiment, R 8 and R 9The halogen in is preferably F, Cl, Br, or I, for example, F or Cl.

[0262] In one embodiment, R 8 and R 9 The C1-C6 alkyl group in is preferably a C1-C3 alkyl group, such as methyl, ethyl, n-propyl, or isopropyl, and also, for example, methyl.

[0263] In one embodiment, R 8 and R 9 The 3- to 7-membered cycloalkyl group in the above is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl, and also, for example, cyclopropyl.

[0264] In one embodiment, R 8 and R 9 The 3- to 7-membered heterocycloalkyl in the above is preferably a 3- to 6-membered heterocycloalkyl, the heteroatom in the 3- to 6-membered heterocycloalkyl is preferably N or O, the number of heteroatoms in the 3- to 6-membered heterocycloalkyl is preferably one or two, the 3- to 6-membered heterocycloalkyl is, for example, a 4-membered heterocycloalkyl, or, for example, oxetane.

[0265] In one embodiment, R g The halogen in is preferably F, Cl, Br, or I, for example, F or Cl.

[0266] In one embodiment, R g The C1-C3 alkyl group in the above is preferably methyl, ethyl, n-propyl, or isopropyl, for example, methyl.

[0267] In one embodiment, R gThe C1-C3 alkoxys in the above are preferably methoxy, ethoxy, n-propoxy, or isopropoxy.

[0268] In one embodiment, the 3- to 7-membered cycloalkyl group in B is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl.

[0269] In one embodiment, the 4- to 7-membered cycloalkyl group in B is preferably a 3- to 6-membered cycloalkyl group, such as cyclobutyl or cyclopentyl.

[0270] In one embodiment, the 4- to 6-membered heterocycloalkyl in B is preferably a 4-membered heterocycloalkyl, a 5-membered heterocycloalkyl, or a 6-membered heterocycloalkyl, and the heteroatom in the 4-membered heterocycloalkyl, 5-membered heterocycloalkyl, and 6-membered heterocycloalkyl is preferably N, and the number of heteroatoms in the 4- to 6-membered heterocycloalkyl is preferably one or two, for example, the 4- to 6-membered heterocycloalkyl is a 4-membered azacycloalkyl (for example,

[0271] [ka]

[0272] ) or 5-membered azacycloalkyl (for example,

[0273] [ka]

[0274] )

[0275] In one embodiment, the 6-10 membered aryl in B is preferably phenyl or naphthyl, for example, phenyl.

[0276] In one embodiment, R i The halogen in is preferably F, Cl, Br, or I, for example, F or Cl, and also for example, F.

[0277] In one embodiment, R i The C1-C3 alkyl group in the above is preferably methyl, ethyl, n-propyl, or isopropyl, and is also, for example, methyl.

[0278] In one embodiment, R i The 3- to 7-membered cycloalkyl group in the above is preferably a 3- to 6-membered cycloalkyl group, for example, cyclopropyl, cyclobutyl, or cyclopentyl, and also, for example, cyclopropyl or cyclobutyl, and for example, cyclopropyl.

[0279] In one embodiment, R i The 3- to 7-membered heterocycloalkyl group is preferably a 3- to 6-membered heterocycloalkyl group, the heteroatom in the 3- to 6-membered heterocycloalkyl group is preferably N or O, and the number of heteroatoms in the 3- to 6-membered heterocycloalkyl group is preferably one or two.

[0280] In one embodiment, R i-1 The halogen in is preferably F, Cl, Br, or I, for example, F or Cl.

[0281] In one embodiment, R i-1 The C1-C3 alkyl group in the above is preferably methyl, ethyl, n-propyl, or isopropyl.

[0282] In one embodiment, R 11-1 , R 11-2 , R 11-3 and R 11-4 The C1-C3 alkyl groups in this compound are, for example, methyl, ethyl, n-propyl, or isopropyl.

[0283] In one embodiment, R 11-3 and R 11-4 The 3- to 7-membered cycloalkyl group in the above-mentioned material may also be a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl.

[0284] In one embodiment, R 11-3 and R 11-4 The 3- to 7-membered heterocycloalkyl group is preferably a 3- to 6-membered heterocycloalkyl group, the heteroatom in the 3- to 6-membered heterocycloalkyl group is preferably N or O, and the number of heteroatoms in the 3- to 6-membered heterocycloalkyl group is preferably one or two.

[0285] In one embodiment, R 11-1 and R 11-2 The 3- to 7-membered cycloalkyl group in the above is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl.

[0286] In one embodiment, R 11-1 and R 11-2 The 3- to 7-membered heterocycloalkyl group is preferably a 3- to 6-membered heterocycloalkyl group, the heteroatom in the 3- to 6-membered heterocycloalkyl group is preferably N or O, and the number of heteroatoms in the 3- to 6-membered heterocycloalkyl group is preferably one or two.

[0287] In one embodiment, R i-2 The halogen in is preferably F, Cl, Br, or I, for example, F or Cl.

[0288] In one embodiment, R i-2 The C1-C3 alkyl group in the above is preferably methyl, ethyl, n-propyl, or isopropyl.

[0289] In one embodiment, Ri-2 The 3- to 7-membered cycloalkyl group in the above is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl.

[0290] In one embodiment, R i-2 The 3- to 7-membered heterocycloalkyl group is preferably a 3- to 6-membered heterocycloalkyl group, the heteroatom in the 3- to 6-membered heterocycloalkyl group is preferably N or O, and the number of heteroatoms in the 3- to 6-membered heterocycloalkyl group is preferably one or two.

[0291] In one embodiment, the halogen in D is preferably F, Cl, Br, or I, for example, F or Cl.

[0292] In one embodiment, the C1-C6 alkyl in D is preferably a C1-C3 alkyl, such as methyl, ethyl, n-propyl, or isopropyl, and also, for example, methyl.

[0293] In one embodiment, the 3- to 7-membered cycloalkyl group in D is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl, for example, cyclopropyl.

[0294] In one embodiment, the 6-10 membered aryl in D is phenyl or naphthyl.

[0295] In one embodiment, R j The halogen in is preferably F, Cl, Br, or I, for example, F or Cl, and also for example, F.

[0296] In one embodiment, R jThe C1-C3 alkyl group in is preferably methyl, ethyl, n-propyl, or isopropyl, and is also, for example, methyl, ethyl, or isopropyl, and preferably methyl.

[0297] In one embodiment, R j The 3- to 7-membered cycloalkyl group in the above is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl, and also, for example, cyclopropyl.

[0298] In one embodiment, R j The 3- to 7-membered heterocycloalkyl group is preferably a 3- to 6-membered heterocycloalkyl group, the heteroatom in the 3- to 6-membered heterocycloalkyl group is preferably N or O, and the number of heteroatoms in the 3- to 6-membered heterocycloalkyl group is preferably one or two.

[0299] In one embodiment, R 12-1 , R 12-2 , R 12-3 and R 12-4 The C1-C3 alkyl group in is preferably methyl, ethyl, n-propyl, or isopropyl, for example, methyl or ethyl, or for example, methyl, ethyl, or isopropyl.

[0300] In one embodiment, R 12-1 , R 12-2 , R 12-3 and R 12-4 The 3- to 7-membered cycloalkyl group in the above is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl.

[0301] In one embodiment, R 12-1 , R 12-2 , R 12-3 and R 12-4The 3- to 7-membered heterocycloalkyl group is preferably a 3- to 6-membered heterocycloalkyl group, the heteroatom in the 3- to 6-membered heterocycloalkyl group is preferably N or O, and the number of heteroatoms in the 3- to 6-membered heterocycloalkyl group is preferably one or two.

[0302] In one embodiment, R k The halogen in is preferably F, Cl, Br, or I, for example, F or Cl, and also for example, F.

[0303] In one embodiment, R k The C1-C3 alkyl group in the above is preferably methyl, ethyl, n-propyl, or isopropyl.

[0304] In one embodiment, R k The 3- to 7-membered cycloalkyl group in the above is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl.

[0305] In one embodiment, R k The 3- to 7-membered heterocycloalkyl group is preferably a 3- to 6-membered heterocycloalkyl group, the heteroatom in the 3- to 6-membered heterocycloalkyl group is preferably N or O, and the number of heteroatoms in the 3- to 6-membered heterocycloalkyl group is preferably one or two.

[0306] In one embodiment, R k-1 The halogen in is preferably F, Cl, Br, or I, for example, F or Cl, and also for example, F.

[0307] In one embodiment, R k-1 The C1-C3 alkyl group in the above is preferably methyl, ethyl, n-propyl, or isopropyl, for example, methyl.

[0308] In one embodiment, R k-1 The 3- to 7-membered cycloalkyl group in the above is preferably a 3- to 6-membered cycloalkyl group, such as cyclopropyl, cyclobutyl, or cyclopentyl.

[0309] In one embodiment, R k-1 The 3- to 7-membered heterocycloalkyl group is preferably a 3- to 6-membered heterocycloalkyl group, the heteroatom in the 3- to 6-membered heterocycloalkyl group is preferably N or O, and the number of heteroatoms in the 3- to 6-membered heterocycloalkyl group is preferably one or two.

[0310] In some embodiments, the compound represented by formula I is the compound represented by formula I-1, the compound represented by formula I-2, the compound represented by formula I-3, the compound represented by formula I-4, or the compound represented by formula I-5.

[0311] [ka]

[0312] Here, X6 is N or CH, and X1, R i ,X2,X3,X4,X5,Y,Z,m,n,E,R j , R 1 B, D, W, k, F, u, R 8 and R 9 This is as described in any one of the claims of the present invention.

[0313] In some embodiments, the compound represented by formula I-1 is the compound represented by formula I-1-1, the compound represented by formula I-1-2, the compound represented by formula I-1-3, or the compound represented by formula I-1-4.

[0314] [ka]

[0315] Here, R 1, R j Z, n, X6, X2, and X4 are as described in any one of the claims of the present invention.

[0316] In some embodiments, the compound represented by formula I-5 is the compound represented by formula I-5-1,

[0317] [ka]

[0318] Here, R 1 , R 8 , R 9 and R j This is as described in any one of the claims of the present invention.

[0319] In some embodiments, the compound represented by formula I-4 is the compound represented by formula I-4-1,

[0320] [ka]

[0321] Here, B is as described in any one of the claims of the present invention.

[0322] In one embodiment, X1, X2, X3, X4, and X5 are independently -CR 1 -, N, O, S,

[0323] [ka]

[0324] Alternatively, it is a chemical bond, and the number of heteroatoms in X1, X2, X3, X4, and X5 is 0, 1, 2, or 3.

[0325] In one embodiment, X1, X2, X3, X4, and X5 are independently -CR 1 -, N, S,

[0326] [ka]

[0327] Alternatively, it is a chemical bond, and the number of heteroatoms in X1, X2, X3, X4, and X5 is one or two.

[0328] In one embodiment, X1 and X3 are independently N, and X4 and X2 are independently -CR 1 - is

[0329] In one embodiment, X2 and X3 are independently N, and X4 and X1 are independently -CR 1 - is

[0330] In one embodiment, X1 and X4 are independently N, and X2 and X3 are independently -CR 1 - is

[0331] In some embodiments,

[0332] [ka]

[0333] X1, X2, X3, and X4 in this case are independently -CR 1 - or N, and the number of heteroatoms is 0, 1, or 2.

[0334] In some embodiments,

[0335] [ka]

[0336] In this case, Y and Z are independently carbonyl (CO) or -(CR). 2 R 3 ) r- and r is 1, R 2 and R 3 These are independently H, -(CH2)-, -(NHCH2)-, -(NHCH2CH2)- or

[0337] [ka]

[0338] That is the case.

[0339] In some embodiments,

[0340] [ka]

[0341] In this case, m is 2, n is 2, and Y and Z are independently -(CR 2 R 3 ) r - and r is 1, R 2 and R 3 These are independently H.

[0342] In some embodiments,

[0343] [ka]

[0344] This is a benzo-5-membered heterocycloalkyl, where the heteroatom in the 5-membered heterocycloalkyl is N, and the number of heteroatoms is 1, for example,

[0345] [ka]

[0346] And e is independently 1, 2, or 3, and also, for example,

[0347] [ka]

[0348] That is the case.

[0349] In some embodiments,

[0350] [ka]

[0351] This is a benzo-5-membered heterocycloalkyl, where the heteroatom in the 5-membered heterocycloalkyl is N, and the number of heteroatoms is 1, for example,

[0352] [ka]

[0353] That is the case.

[0354] In some embodiments,

[0355] [ka]

[0356] This is a benzo-7-membered heterocycloalkyl, where the heteroatom in the 7-membered heterocycloalkyl is N, and the number of heteroatoms is one or two, for example,

[0357] [ka]

[0358] And e is independently 0, 1, 2, or 3, and also, for example,

[0359] [ka]

[0360] That is the case.

[0361] In some embodiments,

[0362] [ka]

[0363] This is a benzo-7-membered heterocycloalkyl, where the heteroatom in the 7-membered heterocycloalkyl is N, and the number of heteroatoms is one or two, for example,

[0364] [ka]

[0365] That is the case.

[0366] In some embodiments,

[0367] [ka]

[0368] This is a 6-membered heteroaryl condensed 5-membered heterocycloalkyl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is one or two, preferably the heteroatom in the 5-membered heterocycloalkyl is N, and the number of heteroatoms is one, for example,

[0369] [ka]

[0370] And e is independently 0, 1, or 2, and also, for example,

[0371] [ka]

[0372] That is the case.

[0373] In some embodiments,

[0374] [ka]

[0375] This is a 6-membered heteroaryl condensed 5-membered heterocycloalkyl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is one or two, preferably the heteroatom in the 5-membered heterocycloalkyl is N, and the number of heteroatoms is one, for example,

[0376] [ka]

[0377] That is the case.

[0378] In some embodiments,

[0379] [ka]

[0380] This is a 6-membered heteroaryl condensed 5-membered heterocycloalkyl, where the heteroatom in the 6-membered heteroaryl is N, and there are 2 heteroatoms. Preferably, the heteroatom in the 5-membered heterocycloalkyl is N, and there is 1 heteroatom. For example,

[0381] [ka]

[0382] And e is independently 0, 1, or 2.

[0383] In some embodiments,

[0384] [ka]

[0385] This is a 6-membered heteroaryl condensed 5-membered heterocycloalkyl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is 1, for example,

[0386] [ka]

[0387] And e is independently 0, 1, 2, or 3, and also, for example,

[0388] [ka]

[0389] That is the case.

[0390] In some embodiments,

[0391] [ka]

[0392] This is a 6-membered heteroaryl condensed 5-membered heterocycloalkyl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is 1, for example,

[0393] [ka]

[0394] That is the case.

[0395] In some embodiments,

[0396] [ka]

[0397] This is a 6-membered heteroaryl condensed 6-membered heterocycloalkyl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is 1, preferably the heteroatom in the 6-membered heterocycloalkyl is N, and the number of heteroatoms is 1, for example,

[0398] [ka]

[0399] And e is independently 0, 1, 2, or 3, and also, for example,

[0400] [ka]

[0401] That is the case.

[0402] In some embodiments,

[0403] [ka]

[0404] This is a 6-membered heteroaryl condensed 6-membered heterocycloalkyl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is 1, preferably the heteroatom in the 6-membered heterocycloalkyl is N, and the number of heteroatoms is 1, for example,

[0405] [ka]

[0406] That is the case.

[0407] In some embodiments,

[0408] [ka]

[0409] This is a 6-membered heteroaryl condensed 7-membered heterocycloalkyl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is one or two, preferably the heteroatom in the 7-membered heterocycloalkyl is N, and the number of heteroatoms is one, for example,

[0410] [ka]

[0411] And e is independently 0, 1, 2, or 3.

[0412] [ka]

[0413] That is the case.

[0414] In some embodiments,

[0415] [ka]

[0416] This is a 6-membered heteroaryl condensed 7-membered heterocycloalkyl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is one or two, preferably the heteroatom in the 7-membered heterocycloalkyl is N, and the number of heteroatoms is one, for example,

[0417] [ka]

[0418] That is the case.

[0419] In some embodiments,

[0420] [ka]

[0421] This is a 5-membered heteroaryl condensed 5-membered heterocycloalkyl, where the heteroatom in the 5-membered heteroaryl is N or S, and the number of heteroatoms is one or two, preferably the heteroatom in the 5-membered heterocycloalkyl is N, and the number of heteroatoms is one, for example,

[0422] [ka]

[0423] That is the case.

[0424] In some embodiments,

[0425] [ka]

[0426] This is a 5-membered heteroaryl condensed 5-membered heterocycloalkyl, where the heteroatoms in the 5-membered heteroaryl are N and / or S, and the number of heteroatoms is one or two, preferably the heteroatom in the 5-membered heterocycloalkyl is N, and the number of heteroatoms is one, for example,

[0427] [ka]

[0428] That is the case.

[0429] In some embodiments,

[0430] [ka]

[0431] This is a 5-membered heteroaryl condensed 6-membered heterocycloalkyl, where the heteroatom in the 5-membered heteroaryl is N, and the number of heteroatoms is one or two, preferably the heteroatom in the 6-membered heterocycloalkyl is N, and the number of heteroatoms is one, for example,

[0432] [ka]

[0433] And also, for example,

[0434] [ka]

[0435] That is the case.

[0436] In some embodiments,

[0437] [ka]

[0438] This is a 5-membered heteroaryl condensed 6-membered heterocycloalkyl, where the heteroatom in the 5-membered heteroaryl is N, and the number of heteroatoms is 1. Preferably, the heteroatom in the 6-membered heterocycloalkyl is N, and the number of heteroatoms is 1. For example,

[0439] [ka]

[0440] And also, for example,

[0441] [ka]

[0442] That is the case.

[0443] In some embodiments,

[0444] [ka]

[0445] This is a 5-membered heteroaryl condensed 6-membered heterocycloalkyl, where the heteroatom in the 5-membered heteroaryl is N, and the number of heteroatoms is 1. Preferably, the heteroatom in the 6-membered heterocycloalkyl is N, and the number of heteroatoms is 1. For example,

[0446] [ka]

[0447] That is the case.

[0448] In some embodiments,

[0449] [ka]

[0450] X1, X2, X3, X4, and X5 in this case are independently -CR 1 -, N, S,

[0451] [ka]

[0452] Alternatively, it is a chemical bond, and the number of heteroatoms in X1, X2, X3, X4, and X5 is 0, 1, or 2.

[0453] In some embodiments,

[0454] [ka]

[0455] is C-(W) k - and here C is,

[0456] [ka]

[0457] C is a 5-membered heteroaryl, a 6-membered heteroaryl, or phenyl, preferably the heteroatom in the 5-membered heteroaryl is N and the number of heteroatoms is 1 or 2, or the heteroatom in the 6-membered heteroaryl is N and the number of heteroatoms is 1, for example C is pyridyl, phenyl, or

[0458] [ka]

[0459] That is the case.

[0460] In some embodiments,

[0461] [ka]

[0462] In this case, W is -O-, -CH2-, or -NH-.

[0463] In some embodiments, the 5-12 member heteroaryl in B is preferably a 5-6 member heteroaryl, a benzo-5-6 member heteroaryl, a 5-7 member cycloalkyl condensed phenyl, a 5-7 member cycloalkyl condensed 5-6 member heteroaryl, a 5-6 member heteroaryl condensed 5-6 member heteroaryl, a 5-7 member heterocycloalkyl condensed 5-6 member heteroaryl, or a 5-7 member heterocycloalkyl condensed 5-6 member aryl, and more preferably a 5-6 member heteroaryl, a benzo-5-6 member heteroaryl, a 5-6 member heteroaryl condensed 5-6 member heteroaryl, a 5-7 member heterocycloalkyl condensed 5-6 member heteroaryl, or a 5-7 member heterocycloalkyl condensed phenyl.

[0464] In some embodiments, the heteroatom in the 4-6 membered heterocycloalkyl group B is N, and the number of heteroatoms is 1, for example,

[0465] [ka]

[0466] And e is independently 0, 1, 2, or 3, and also, for example,

[0467] [ka]

[0468] That is the case.

[0469] In some embodiments, the heteroatom in the 4-6 membered heterocycloalkyl group B is N, and the number of heteroatoms is 1, for example,

[0470] [ka]

[0471] That is the case.

[0472] In some embodiments, B is two R i A 4-6 member heterocycloalkyl substituted with R on two identical atoms. i These form a 3- to 7-membered cycloalkyl group with the atoms linked to them, and the 3- to 7-membered cycloalkyl group is preferably a 3- to 6-membered cycloalkyl group, for example, B is a 4-membered heterocycloalkyl group or a 5-membered heterocycloalkyl group, and the two R i It forms a 3-4 membered cycloalkyl group, and for example, B is

[0473] [ka]

[0474] That is the case.

[0475] In some embodiments, B is two R i A 4-6 member heterocycloalkyl substituted with R on two identical atoms. i These atoms form a 3-7 membered cycloalkyl group with the atoms linked to them, and the 3-7 membered cycloalkyl group is preferably a 3-6 membered cycloalkyl group, for example, B is a 4 membered heterocycloalkyl group, and two R i It forms a 3-4 membered cycloalkyl group, and for example, B is

[0476] [ka]

[0477] That is the case.

[0478] In some embodiments, B is two R i A 4-6 member heterocycloalkyl substituted with R on two identical atoms. i These atoms form a 3-7 membered cycloalkyl group with the atoms linked to them, and the 3-7 membered cycloalkyl group is preferably a 3-6 membered cycloalkyl group, for example, B is a 5 membered heterocycloalkyl group, and the two R iIt forms a 3-4 membered cycloalkyl group, and for example, B is

[0479] [ka]

[0480] That is the case.

[0481] In some embodiments, B is two R i It is a 4-6 member heterocycloalkyl substituted in the ortho position, with two adjacent R i These atoms form a 3- to 7-membered cycloalkyl group with the atoms linked to them (where the 3- to 7-membered cycloalkyl group forms a fused ring with B), and the 3- to 7-membered cycloalkyl group is preferably a 3- to 6-membered cycloalkyl group, for example, B is a 5-membered heterocycloalkyl group, and the two R i These form a three-membered cycloalkyl group with the atoms linked to them, and for example, B is

[0482] [ka]

[0483] That is the case.

[0484] In some embodiments, B is a 5-membered heteroaryl, where the heteroatoms in the 5-membered heteroaryl are N and / or S, and the number of heteroatoms is one or two, for example,

[0485] [ka]

[0486] That is the case.

[0487] In some embodiments, B is a 5-membered heteroaryl, where the heteroatoms in the 5-membered heteroaryl are N or S, and the number of heteroatoms is one or two, for example,

[0488] [ka]

[0489] That is the case.

[0490] In some embodiments, B is a 6-membered heteroaryl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is one or two, for example,

[0491] [ka]

[0492] That is the case.

[0493] In some embodiments, the 6- to 10-membered aryl group in B is, for example, phenyl.

[0494] In some embodiments, B is a benzo-5-membered heterocycloalkyl, where the heteroatom in the 5-membered heterocycloalkyl is N, and the number of heteroatoms is 1, for example,

[0495] [ka]

[0496] And e is independently 0, 1, 2, or 3, and also, for example,

[0497] [ka]

[0498] That is the case.

[0499] In some embodiments, B is a benzo-5-membered heterocycloalkyl, where the heteroatom in the 5-membered heterocycloalkyl is N, and the number of heteroatoms is 1, for example,

[0500] [ka]

[0501] That is the case.

[0502] In some embodiments, B is a benzo-6-membered heteroaryl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is one or two, for example,

[0503] [ka]

[0504] That is the case.

[0505] In some embodiments, B is a benzo-6-membered heterocycloalkyl, where the heteroatoms in the 6-membered heterocycloalkyl are N and / or O, and the number of heteroatoms is one or two, for example,

[0506] [ka]

[0507] That is the case.

[0508] In some embodiments, B is a benzo-6-membered heterocycloalkyl, where the heteroatoms in the 6-membered heterocycloalkyl are N or O, and the number of heteroatoms is one or two, for example,

[0509] [ka]

[0510] That is the case.

[0511] In some embodiments, B is a 6-membered heteroaryl condensed 5-membered heteroaryl, where the heteroatom in the 6-membered heteroaryl is N and there is one heteroatom; preferably, the heteroatom in the 5-membered heteroaryl is N or S and there is one heteroatom; for example,

[0512] [ka]

[0513] That is the case.

[0514] In some embodiments, B is a 6-membered heteroaryl condensed 6-membered heterocycloalkyl, where the heteroatom in the 6-membered heteroaryl is N and there is one heteroatom, preferably the heteroatom in the 6-membered heterocycloalkyl is O and there is one heteroatom, for example,

[0515] [ka]

[0516] That is the case.

[0517] In some embodiments, the 5-12 member heteroaryl in D is preferably a 5-6 member heteroaryl, a benzo-5-6 member heteroaryl, a 5-7 member cycloalkyl condensed phenyl, a 5-7 member cycloalkyl condensed 5-6 member heteroaryl, a 5-6 member heteroaryl condensed 5-6 member heteroaryl, a 5-7 member heterocycloalkyl condensed 5-6 member heteroaryl, or a 5-7 member heterocycloalkyl condensed 5-6 member aryl, and more preferably a 5-6 member heteroaryl, a benzo-5-6 member heteroaryl, a 5-7 member cycloalkyl condensed 5-6 member heteroaryl, a 5-6 member heteroaryl condensed 5-6 member heteroaryl, a 5-7 member heterocycloalkyl condensed 5-6 member heteroaryl, or a 5-7 member heterocycloalkyl condensed phenyl.

[0518] In some embodiments, the 5-12 membered heteroaryl in D is a 5-6 membered heteroaryl, a benzo-5-6 membered heteroaryl, a 5-7 membered cycloalkyl condensed 5-6 membered heteroaryl, a 5-6 membered heteroaryl condensed 5-6 membered heteroaryl, a 5-7 membered heterocycloalkyl condensed 5-6 membered heteroaryl, or a 5-7 membered heterocycloalkyl condensed phenyl, where the heteroatoms in the 5-6 membered heteroaryl and 5-7 membered heterocycloalkyl are preferably selected from one, two, or three of N, O, and S, and the number of heteroatoms is preferably one, two, or three.

[0519] In some embodiments, the 5-6 membered heteroaryl in D is preferably a 5-membered heteroaryl or a 6-membered heteroaryl.

[0520] In some embodiments, D is hydrogen, methyl, ethyl, isopropyl, cyclopropyl, or trifluoromethyl.

[0521] In some embodiments, D is a 6-membered heteroaryl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is one or two, for example,

[0522] [ka]

[0523] And e is independently 0, 1, 2, or 3, and also, for example,

[0524] [ka]

[0525] That is the case.

[0526] In some embodiments, D is a 6-membered heteroaryl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is one or two, for example,

[0527] [ka]

[0528] That is the case.

[0529] In some embodiments, D is a five-membered heteroaryl molecule, where the heteroatoms in the five-membered heteroaryl molecule are one or more of N, O, and S, and the number of heteroatoms is one, two, or three, for example,

[0530] [ka]

[0531] That is the case.

[0532] In some embodiments, D is a 5-membered heteroaryl, where the heteroatoms in the 5-membered heteroaryl are N and / or S, and the number of heteroatoms is 1, 2, or 3, for example,

[0533] [ka]

[0534] That is the case.

[0535] In some embodiments, D is a 5-membered heteroaryl, where the heteroatoms in the 5-membered heteroaryl are N or S, and the number of heteroatoms is 1, 2, or 3, for example,

[0536] [ka]

[0537] That is the case.

[0538] In some embodiments, D is a 6-membered heteroaryl condensed 5-membered heterocycloalkyl, where the heteroatom in the 6-membered heteroaryl is N and there is one heteroatom, preferably the heteroatom in the 5-membered heterocycloalkyl is N or O and there is one heteroatom, for example,

[0539] [ka]

[0540] And e is independently 0, 1, 2, or 3, and also, for example,

[0541] [ka]

[0542] That is the case.

[0543] In some embodiments, D is a 6-membered heteroaryl condensed 5-membered heterocycloalkyl, where the heteroatom in the 6-membered heteroaryl is N and there is one heteroatom, preferably the heteroatom in the 5-membered heterocycloalkyl is N or O and there is one heteroatom, for example,

[0544] [ka]

[0545] That is the case.

[0546] In some embodiments, D is a 6-membered heteroaryl condensed 5-membered cycloalkyl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is 1, for example,

[0547] [ka]

[0548] And e is independently 0, 1, 2, or 3, and also, for example,

[0549] [ka]

[0550] That is the case.

[0551] In some embodiments, D is a 6-membered heteroaryl condensed 5-membered cycloalkyl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is 1, for example,

[0552] [ka]

[0553] That is the case.

[0554] In some embodiments, D is a benzo-5-membered heteroaryl, where the heteroatoms in the 5-membered heteroaryl are N and / or S, and the number of heteroatoms is 2, for example,

[0555] [ka]

[0556] And e is independently 0, 1, 2, or 3, and also, for example,

[0557] [ka]

[0558] That is the case.

[0559] In some embodiments, D is a 5-6 member heteroaryl condensate, where the heteroatoms in the 5-6 member heteroaryl are N and / or S, and the number of heteroatoms is one, two, or three, for example,

[0560] [ka]

[0561] And e is independently 0, 1, 2, or 3.

[0562] In some embodiments, D is a 5-6 member heteroaryl condensed 5-6 member heterocycloalkyl, where the heteroatom in the 5-6 member heteroaryl is N, and the number of heteroatoms is 1, 2, or 3, preferably the heteroatom in the 5-6 member heterocycloalkyl is O, and the number of heteroatoms is 1, 2, or 3, for example,

[0563] [ka]

[0564] And e is independently 0, 1, 2, or 3.

[0565] In some embodiments, D is a benzo-5-6 member heterocycloalkyl, where the heteroatoms in the 5-6 member heterocycloalkyl are selected from one or more of O, N, and O, and the heteroatoms are one, two, or three, for example,

[0566] [ka]

[0567] And e is independently 0, 1, 2, or 3.

[0568] In some embodiments, D is a benzo-5-6 membered heteroaryl, where the heteroatom in the 5-6 membered heteroaryl is N, and the number of heteroatoms is one, two, or three, for example,

[0569] [ka]

[0570] And e is independently 0, 1, 2, or 3.

[0571] In one embodiment,

[0572] [ka]

[0573] Preferably, it is a 6-membered heteroaryl condensed 5-membered heterocycloalkyl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is 2, for example,

[0574] [ka]

[0575] And e is independently 0, 1, or 2, and also, for example,

[0576] [ka]

[0577] That is the case.

[0578] In one embodiment,

[0579] [ka]

[0580] Preferably, it is a 6-membered heteroaryl condensed 5-membered heterocycloalkyl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is 2, for example,

[0581] [ka]

[0582] That is the case.

[0583] In one embodiment,

[0584] [ka]

[0585] Preferably, it is a 6-membered heteroaryl condensed 7-membered heterocycloalkyl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is one or two, for example,

[0586] [ka]

[0587] That is the case.

[0588] In one embodiment, E in L is preferably a carbonyl, F is a chemical bond, t is 0, and u is 1.

[0589] In one embodiment, B is preferably a four-membered heterocycloalkyl, where the heteroatom in the four-membered heterocycloalkyl is N, and the number of heteroatoms is one or two, for example,

[0590] [ka]

[0591] That is the case.

[0592] In one embodiment, D is preferably a 6-membered heteroaryl, where the heteroatom in the 6-membered heteroaryl is N, and the number of heteroatoms is one or two, for example,

[0593] [ka]

[0594] That is the case.

[0595] In one preferred embodiment, the compound represented by formula I or a pharmaceutically acceptable salt thereof,

[0596] [ka]

[0597] Here,

[0598] [ka]

[0599] z is

[0600] [ka]

[0601] And, m is a natural number between 0 and 3. n is a natural number between 0 and 3, and m and n are not both 0 at the same time. k is a natural number between 0 and 3. X1, X2, X3, X4, and X5 are independently -CR 1 -, N, S,

[0602] [ka]

[0603] or chemical bond, R N-1 These are hydrogen, C1-C6 alkyl or 3-7 membered cycloalkyl, Y and Z are independently carbonyl (CO) or -(CR) 2 R 3 ) r - and r is a natural number between 0 and 5. Each W is independently -O-, -(CR 4 R 5 )-, -NR 6 -or chemical bond, Each R 1 These are independently hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, or -NR 1-1 R 1-2 Here, the C1-C6 alkylthio, C1-C6 alkyl, and C1-C6 alkoxy are independently one, two, three, or four R a Replaced by choice, Each R aThese are independently halogens, hydroxyls, C1-C6 alkoxys, or -NRs. 1-4 R 1-5 And, R 1-1 and R 1-2 R is independently hydrogen or a C1-C6 alkyl group, where the C1-C6 alkyl group is independently one, two, three, or four R groups. b Replaced by any choice, or R 1-1 and R 1-2 These atoms form a 3-7 member heterocycloalkyl group with the atoms linked to them, where the 3-7 member heterocycloalkyl group has one, two, three or four R atoms. b-2 Replaced by choice, Each R b These are independently hydroxy, 3-7 membered cycloalkyl, or C1-C3 alkyl groups. Each R b-2 These are independently halogens or C1-C6 alkyls. R 1-4 and R 1-5 R is independently hydrogen or a C1-C3 alkyl group, where the C1-C3 alkyl group is independently one, two, three, or four R groups. 1-4-1 Replaced by any choice, or R 1-4 and R 1-5 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. Each R 1-4-1 It is independently a halogen, R 2 and R 3 It is independently hydrogen or NR 2-1 R 2-2 And, R 2-1 and R 2-2 These are independently hydrogen or C1-C6 alkyl groups. R 4 , R 5 and R 6 It is independently hydrogen or NR 4-1 R 4-2 And, R 4-1 and R 4-2 It is independently hydrogen, L is

[0604] [ka]

[0605] And, t is a natural number between 0 and 3. u is a natural number between 0 and 3. E is carbonyl,

[0606] [ka]

[0607] , -NHCO- or chemical bond, F is carbonyl,

[0608] [ka]

[0609] , -O-, -NH- or chemical bond, R 8 and R 9 R is independently hydrogen or a C1-C6 alkyl group, or 8 and R 9 These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them. B is a 4-6 member heterocycloalkyl, a 6-10 member aryl, or a 5-12 member heteroaryl, where the 4-6 member heterocycloalkyl, 6-10 member aryl, and 5-12 member heteroaryl are independently one, two, or three R i Replaced by choice, Each R i These are independently hydrogen, halogen, hydroxyl, or C1-C3 alkyl, or R on two identical atoms. i These atoms form a 3-7 membered cycloalkyl group with the atoms linked to them, or two adjacent R i These form 3-7 membered cycloalkyl groups with the atoms linked to them. D is hydrogen, a C1-C6 alkyl group, or a 5-12 member heteroaryl group, where the C1-C6 alkyl group and the 5-12 member heteroaryl group are independently one, two, or three R groups. j Replaced by choice, Each R j These are independently hydrogen, halogen, C1-C3 alkyl, 3-7 membered cycloalkyl, and -OR 12-3 or -SR 12-4 The C1-C3 alkyl and 3-7 membered cycloalkyl groups are independently one, two, or three R groups. k Replaced by choice, R 12-3 and R 12-4 These are independently C1-C3 alkyl groups, where the C1-C3 alkyl group independently has one, two, or three R groups. k-1 Replaced by choice, Each R k It is independently a halogen, Each R k-1 It is independently a halogen, In the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl, the heteroatoms are selected from one or more of N, O, and S, and the number of heteroatoms is 1 to 3.

[0610] In one preferred embodiment, the compound represented by formula I or a pharmaceutically acceptable salt thereof,

[0611] [ka]

[0612] Here,

[0613] [ka]

[0614] teeth,

[0615] [ka]

[0616] And, m is a natural number between 0 and 3. n is a natural number between 0 and 3, and m and n are not both 0 at the same time. k is a natural number between 0 and 3. X1, X2, X3, X4, and X5 are independently -CR 1 -, N, S,

[0617] [ka]

[0618] or chemical bond, R N-1 These are C1-C6 alkyl groups, Y and Z are independently carbonyl (CO) or -(CR) 2 R 3 ) r - and r is a natural number between 0 and 5. Each W is independently -(CR 4 R 5 )-, -NR 6 -or chemical bond, Each R 1 These are independently hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, or -NR 1-1 R 1-2 Here, the C1-C6 alkylthio, C1-C6 alkyl, and C1-C6 alkoxy are independently one, two, three, or four R a Replaced by choice, Each R a These are independently hydroxy, C1-C6 alkoxy, or -NR 1-4 R 1-5 And, R 1-1 and R 1-2R is independently hydrogen or a C1-C6 alkyl group, where the C1-C6 alkyl group is independently one, two, three, or four R groups. b Replaced by any choice, or R 1-1 and R 1-2 These atoms form a 3-7 member heterocycloalkyl group with the atoms linked to them, where the 3-7 member heterocycloalkyl group has one, two, three or four R atoms. b-2 Replaced by choice, Each R b These are independently 3- to 7-membered cycloalkyl groups. Each R b-2 These are independently halogens or C1-C6 alkyls. R 1-4 and R 1-5 These are independently C1-C3 alkyl groups, R 2 and R 3 It is independently hydrogen or NR 2-1 R 2-2 And, R 2-1 and R 2-2 It is independently hydrogen, R 4 , R 5 and R 6 It is independently hydrogen, L is

[0619] [ka]

[0620] And, t is a natural number between 0 and 3. u is a natural number between 0 and 3. E is carbonyl,

[0621] [ka]

[0622] , -NHCO- or chemical bond, F is a chemical bond, R 8 and R 9 R is independently hydrogen or a C1-C6 alkyl group, or 8 and R 9 These form 3-7 membered cycloalkyl groups with the atoms linked to them. B is a 4-6 member heterocycloalkyl, a 6-10 member aryl, or a 5-12 member heteroaryl, where the 4-6 member heterocycloalkyl, 6-10 member aryl, and 5-12 member heteroaryl are independently one, two, or three R i Replaced by choice, Each R i These are independently hydrogen, halogen, hydroxyl, or C1-C3 alkyl, or R on two identical atoms. i These form 3-7 membered cycloalkyl groups with the atoms linked to them. D is hydrogen, a C1-C6 alkyl group, or a 5-12 member heteroaryl group, where the C1-C6 alkyl group and the 5-12 member heteroaryl group are independently one, two, or three R groups. j Replaced by choice, Each R j These are independently hydrogen, halogen, C1-C3 alkyl, 3-7 membered cycloalkyl, and -OR 12-3 or -SR 12-4 The C1-C3 alkyl and 3-7 membered cycloalkyl groups are independently one, two, or three R groups. k Replaced by choice, R 12-3 and R 12-4 These are independently C1-C3 alkyl groups, where the C1-C3 alkyl group independently has one, two, or three R groups. k-1 Replaced by choice, Each R k It is independently a halogen, Each R k-1 It is independently a halogen, In the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 3.

[0623] In one preferred embodiment, the compound represented by formula I or a pharmaceutically acceptable salt thereof,

[0624] [ka]

[0625] Here,

[0626] [ka]

[0627] teeth,

[0628] [ka]

[0629] And, m is a natural number between 1 and 3. n is a natural number between 1 and 3. k is a natural number between 1 and 3. X1, X2, X3, X4, and X5 are independently -CR 1 -, N, O, S,

[0630] [ka]

[0631] or chemical bond, and the number of heteroatoms in X1, X2, X3, X4 and X5 is 0, 1, 2 or 3. R N-1 is hydrogen or C1-C6 alkyl, Y and Z are independently carbonyl (CO) or -(CR) 2 R 3 ) r - and r is a natural number between 1 and 2. Each W is independently -O-, -(CR 4 R5 )-, -NR 6 -or chemical bond, Each R 1 These are independently hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, or -NR 1-1 R 1-2 Here, the C1-C6 alkyl and C1-C6 alkoxy are independently one, two, three, or four R a Replaced by choice, Each R a These are independently hydroxy, C1-C3 alkoxy, or NR 1-4 R 1-5 And, R 1-1 and R 1-2 R is independently hydrogen or a C1-C6 alkyl group, where the C1-C6 alkyl group is independently one, two, three, or four R groups. b Replaced by any choice, or R 1-1 and R 1-2 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. Each R b These are independently hydroxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, C1-C3 alkyl, C1-C3 alkoxy, or NR 1-1-1 R 1-2-1 Here, the 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, and C1-C3 alkyl groups are independently one, two, three, or four R groups. b-1 Replaced by choice, Each R b-1 It is independently hydroxyl, R 1-4 and R 1-5 R is independently hydrogen or a C1-C3 alkyl group, where the C1-C3 alkyl group is independently one, two, three, or four R groups. 1-4-1 Replaced by any choice, or R 1-4 and R 1-5 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. Each R 1-4-1It is independently a halogen, R 1-1-1 and R 1-2-1 These are independently hydrogen or C1-C3 alkyl groups. R 2 and R 3 It is independently hydrogen or NR 2-1 R 2-2 And, R 2-1 and R 2-2 These are independently hydrogen or C1-C6 alkyl groups. R 4 , R 5 and R 6 It is independently hydrogen, L is

[0632] [ka]

[0633] And, t is a natural number between 0 and 2. u is a natural number between 0 and 2. E is a carbonyl, -NHCO-, or chemical bond. F is -O-, -NH-, or a chemical bond. R 8 and R 9 R is independently hydrogen or a C1-C6 alkyl group, or 8 and R 9 These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them. B is a 4-6 member heterocycloalkyl, a 6-10 member aryl, or a 5-12 member heteroaryl, where the 5-12 member heteroaryl, 6-10 member aryl, and 4-6 member heterocycloalkyl are independently one, two, or three R i Replaced by choice, Each R i These are independently hydrogen, hydroxyl, halogen, or C1-C3 alkyl, or two R iThese atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, or two adjacent R i These atoms form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them (where the 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups form a fused ring with B), D is hydrogen, a 3-7 membered cycloalkyl, a C1-C6 alkyl, or a 5-12 membered heteroaryl, where the C1-C6 alkyl and 5-12 membered heteroaryl are independently one, two, or three R j Replaced by choice, Each R j These are independently halogens, C1-C3 alkyls, and -OR 12-3 or -SR 12-4 The C1-C3 alkyl groups are independently one, two, or three R groups. k Replaced by any choice, each R k It is independently a halogen, R 12-3 and R 12-4 These are independently C1-C3 alkyl groups, and each of the C1-C3 alkyl groups independently has one, two, or three R groups. k Replaced by any choice, each R k It is independently a halogen, In the 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl compounds, the heteroatoms are N, O, or S, and the number of heteroatoms is 1 to 3; or, in the 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl compounds, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 3.

[0634] In one preferred embodiment, the compound represented by formula I or a pharmaceutically acceptable salt thereof,

[0635] [ka]

[0636] Here,

[0637] [ka]

[0638] teeth,

[0639] [ka]

[0640] And, m is a natural number between 1 and 3. n is a natural number between 1 and 3. X1, X2, X3, and X4 are independently -CR 1 -, N, S,

[0641] [ka]

[0642] or chemical bond, and the number of heteroatoms in X1, X2, X3, X4 and X5 is one or two. R N-1 These are C1-C6 alkyl groups, Y and Z are independently carbonyl (CO) or -(CR) 2 R 3 ) r - and r is a natural number between 1 and 2. Each R 1 These are independently hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, or -NR 1-1 R 1-2 Here, the C1-C6 alkyl and C1-C6 alkoxy are independently one, two, three, or four R a Replaced by choice, Each R a These are independently hydroxy, C1-C3 alkoxy, or NR 1-4 R1-5 And, R 1-1 and R 1-2 R is independently hydrogen or a C1-C6 alkyl group, where the C1-C6 alkyl group is independently one, two, three, or four R groups. b Replaced by any choice, or R 1-1 and R 1-2 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. Each R b These are independently hydroxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, C1-C3 alkyl, C1-C3 alkoxy, or NR 1-1-1 R 1-2-1 Here, the 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, and C1-C3 alkyl groups are independently one, two, three, or four R groups. b-1 Replaced by choice, Each R b-1 It is independently hydroxyl, R 1-4 and R 1-5 R is independently hydrogen or a C1-C3 alkyl group, where the C1-C3 alkyl group is independently one, two, three, or four R groups. 1-4-1 Replaced by any choice, or R 1-4 and R 1-5 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. R 1-1-1 and R 1-2-1 These are independently hydrogen or C1-C3 alkyl groups. R 1-4-1 It is a halogen, R 2 and R 3 It is independently hydrogen, L is

[0643] [ka]

[0644] And, t is a natural number between 0 and 2. u is a natural number between 0 and 2. E is a carbonyl or chemical bond, F is -O-, -NH-, or a chemical bond. R 8 and R 9 These are independently C1-C6 alkyl groups, or R 8 and R 9 These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them. B is a 4-6 member heterocycloalkyl or a 5-12 member heteroaryl, where the 5-12 member heteroaryl and 4-6 member heterocycloalkyl are independently one, two or three R i Replaced by choice, Each R i These are independently hydrogen, hydroxyl, halogen, or C1-C3 alkyl, or two R i These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, or two adjacent R i These atoms form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them (where the 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups form a fused ring with B), D is hydrogen, a 3-7 membered cycloalkyl, a C1-C6 alkyl, or a 5-6 membered heteroaryl, where the C1-C6 alkyl and 5-6 membered heteroaryl are independently one, two, or three R j Replaced by choice, Each R j These are independently halogens or C1-C3 alkyl groups, and the C1-C3 alkyl group independently has one, two, or three R groups. k Replaced by any choice, each R k It is independently a halogen, In the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, 5-6 member heteroaryl, and 5-12 member heteroaryl compounds, the heteroatoms are N, O, or S, and the number of heteroatoms is 1 to 3. Alternatively, in the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, 5-6 member heteroaryl, and 5-12 member heteroaryl compounds, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 3.

[0645] In one preferred embodiment, the compound represented by formula I or a pharmaceutically acceptable salt thereof,

[0646] [ka]

[0647] Here,

[0648] [ka]

[0649] teeth,

[0650] [ka]

[0651] And, m is a natural number between 1 and 2. n is a natural number between 1 and 2. k is a natural number between 1 and 3. X1, X2, X3, X4, and X5 are independently -CR 1 -, N, O, S,

[0652] [ka]

[0653] or chemical bond, and the number of heteroatoms in X1, X2, X3, X4 and X5 is 0, 1, 2 or 3. R N-1 These are C1-C6 alkyl groups, Each W is independently -(CR 4 R 5 )-, -O-, -NR 6 - or a chemical bond, where Y and Z are independently carbonyl (CO) or -(CR) 2 R 3 ) r - and r is a natural number between 1 and 2. Each R 1 These are independently hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, or -NR 1-1 R 1-2 Here, the C1-C6 alkyl and C1-C6 alkoxy are independently one, two, three, or four R a Replaced by choice, Each R a These are independently hydroxy, C1-C3 alkoxy, or NR 1-4 R 1-5 And, R 1-1 and R 1-2 R is independently hydrogen or a C1-C6 alkyl group, where the C1-C6 alkyl group is independently one, two, three, or four R groups. b Replaced by any choice, or R 1-1 and R 1-2 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. Each R b These are independently hydroxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, C1-C3 alkyl, C1-C3 alkoxy, or NR 1-1-1 R 1-2-1 Here, the 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, and C1-C3 alkyl groups are independently one, two, three, or four R groups. b-1 Replaced by choice, Each R b-1 It is independently hydroxyl, R 1-4 and R 1-5 R is independently hydrogen or a C1-C3 alkyl group, where the C1-C3 alkyl group is independently one, two, three, or four R groups. 1-4-1 Replaced by any choice, or R 1-4 and R 1-5 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. R 1-1-1 and R 1-2-1 These are independently hydrogen or C1-C3 alkyl groups. Each R 1-4-1 It is independently a halogen, R 2 and R 3 It is independently hydrogen or NR 2-1 R 2-2 And, R 2-1 and R 2-2 These are independently hydrogen or C1-C6 alkyl groups. R 4 , R 5 and R 6 is independently hydrogen, and L is,

[0654] [ka]

[0655] And, t is a natural number between 0 and 2. u is a natural number between 0 and 2. E is a carbonyl, -NHCO-, or chemical bond. F is -O-, -NH-, or a chemical bond. R 8 and R 9 R is independently hydrogen or a C1-C6 alkyl group, or 8 and R 9 These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them. B is a 4-6 member heterocycloalkyl, a 6-10 member aryl, or a 5-12 member heteroaryl, where the 5-12 member heteroaryl, 6-10 member aryl, and 4-6 member heterocycloalkyl are independently one, two, or three R i Replaced by choice, Each R i These are independently hydrogen, hydroxyl, halogen, or C1-C3 alkyl, or two R i These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, or two adjacent R i These atoms form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with the atoms linked to them (where the 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups form a fused ring with B), D is hydrogen, a C1-C6 alkyl group, or a 5-12 member heteroaryl group, where the C1-C6 alkyl group and the 5-12 member heteroaryl group are independently one, two, or three R groups. j Replaced by choice, Each R j These are independently halogens, C1-C3 alkyls, and OR 12-3 or SR 12-4 The C1-C3 alkyl groups are independently one, two, or three R groups. k Replaced by any choice, each R k It is independently a halogen, R 12-3 and R 12-4 These are independently C1-C3 alkyl groups, where the C1-C3 alkyl group independently has one, two, or three R groups. k-1 Replaced by any choice, each R k-1 The first is a halogen, and the heteroatoms in the 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl are N, O, or S, with 1 to 3 heteroatoms; or the second is one or more of N, O, and S, with 1 to 3 heteroatoms.

[0656] In one preferred embodiment, the compound represented by formula I or a pharmaceutically acceptable salt thereof,

[0657] [ka]

[0658] Here,

[0659] [ka]

[0660] teeth,

[0661] [ka]

[0662] And, m is 1, n is 1, X1, X2, X3, and X4 are independently -CR 1 - or N, and the number of heteroatoms in X1, X2, X3 and X4 is 2. Y and Z are independently -(CR 2 R 3 ) r - and r is 1, Each R 1 These are independently C1-C6 alkyl (e.g., methyl) or C1-C6 alkoxy (e.g., methoxy), R 2 and R 3 It is independently hydrogen, L is

[0663] [ka]

[0664] And, t is 0, u is 1, E is a carbonyl group, F is a chemical bond, B is a 4-6 member heterocycloalkyl, where the 4-6 member heterocycloalkyl is independently one, two, or three R i Replaced by choice, Each R i It is independently hydrogen, D is a 5-12 member heteroaryl, where the 5-12 member heteroaryl is independently one, two, or three R j (For example, one) is used to optionally replace it. Each R j These are independently -OR 12-3 And, R 12-3 The C1-C3 alkyl group is a C1-C3 alkyl group (e.g., ethyl or isopropyl), and the C1-C3 alkyl group may independently have one, two, or three R groups. k Replaced by any choice, each R k These are independently halogens (e.g., F), In the aforementioned 4-6 member heterocycloalkyl and 5-12 member heteroaryl compounds, the heteroatoms are N, O, or S, and the number of heteroatoms is 1 to 3; or, in the aforementioned 4-6 member heterocycloalkyl and 5-12 member heteroaryl compounds, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 3. A

[0665] [ka]

[0666] In this case, the number of heteroatoms in X1, X2, and X4 is one or two. A

[0667] [ka]

[0668] and when L is carbonyl, u is a natural number from 1 to 3, B is a 4- to 6-member heterocycloalkyl, and the 4- to 6-member heterocycloalkyl is independently substituted by one, two or three R i optionally.

[0669] In one preferred embodiment, it is the compound represented by the formula I or a pharmaceutically acceptable salt thereof, where

[0670]

Chemical formula

[0671] is

[0672]

Chemical formula

[0673] and m is 1, n is 1, X2 and X3 are N, X1 and X4 are independently -CR 1 -. Y and Z are independently -(CR 2 R 3 ) r -, r is 1, each R 1 is independently hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, 3- to 7-member cycloalkyl, 3- to 7-member heterocycloalkyl or -NR 1-1 R 1-2 , where the C1-C6 alkyl and C1-C6 alkoxy are independently substituted by one, two, three or four R a optionally, R 1-1 and R 1-2 are independently hydrogen or C1-C6 alkyl, or R 1-1 and R1-2 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. Each R a These are independently hydroxy, C1-C6 alkoxy, or NR 1-4 R 1-5 And, R 1-4 and R 1-5 These are independently hydrogen or C1-C3 alkyl groups. R 2 and R 3 It is independently hydrogen, L is

[0674] [ka]

[0675] And, t is 0, u is 1, E is a carbonyl group, F is a chemical bond, B is a 4-6 member heterocycloalkyl, where the 4-6 member heterocycloalkyl is independently one, two, or three R i Replaced by choice, Each R i These are independently hydrogen, halogen, hydroxyl, or C1-C3 alkyl, D is a 5-12 member heteroaryl, where the 5-12 member heteroaryl is independently one, two, or three R j It is optionally substituted by, preferably, D is a 5-6 member heteroaryl, where the 5-6 member heteroaryl is independently one, two or three R j The heteroatoms in the 5-6 member heteroaryl are selected from one, two, or three of N, S, and O, and the number of heteroatoms is one, two, or three. Each R j These are independently H, halogen, C1-C3 alkyl, OR 12-3 or SR 12-4Here, the C1-C3 alkyl groups are independently one, two, or three R k Replaced by choice, R 12-3 and R 12-4 These are independently C1-C3 alkyl groups, and each of the C1-C3 alkyl groups independently has one, two, or three R groups. k-1 Replaced by choice, Each R k These are independently halogens or C1-C3 alkyls. Each R k-1 These are independently halogens or C1-C3 alkyls. In the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 3.

[0676] In one preferred embodiment, the compound represented by formula I or a pharmaceutically acceptable salt thereof, Here,

[0677] [ka]

[0678] teeth,

[0679] [ka]

[0680] And, m is 1, n is 1, X1 and X3 are N, X2 and X4 are independently -CR 1 -and, Y and Z are independently -(CR 2 R 3 ) r - and r is 1, Each R 1These are independently hydrogen, halogen, cyano, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, or -NR 1-1 R 1-2 Here, the C1-C6 alkyl, C1-C6 alkoxy, and C1-C6 alkylthio are independently one, two, three, or four R a Replaced by choice, R 1-1 and R 1-2 R is independently hydrogen or a C1-C6 alkyl group, or 1-1 and R 1-2 These form 3-7 member heterocycloalkyl groups with the atoms linked to them. Each R a These are independently hydroxy, C1-C6 alkoxy, or NR 1-4 R 1-5 And, R 1-4 and R 1-5 These are independently hydrogen or C1-C3 alkyl groups. R 2 and R 3 It is independently hydrogen, L is

[0681] [ka]

[0682] And, t is 0, u is 1, E is a carbonyl group, F is a chemical bond, B is a 4-6 member heterocycloalkyl, where the 4-6 member heterocycloalkyl is independently one, two, or three R i Replaced by choice, Each R i These are independently hydrogen, halogen, hydroxyl, or C1-C3 alkyl, or two R i These form 3-7 membered cycloalkyl groups with the atoms linked to them. D is a 5- to 12-member heteroaryl, where the 5- to 12-member heteroaryl is independently optionally substituted by one, two or three Rs j and preferably, D is a 5- to 6-member heteroaryl, where the 5- to 6-member heteroaryl is independently optionally substituted by one, two or three Rs j and the heteroatoms in the 5- to 6-member heteroaryl are selected from one, two or three of N, S and O, and the number of heteroatoms is one, two or three Each R j is independently hydrogen, halogen, cyano, hydroxy, C1-C3 alkyl, 3- to 7-member cycloalkyl, 3- to 7-member heterocycloalkyl, -NR 12-1 R 12-2 , -OR 12-3 or -SR 12-4 where the C1-C3 alkyl, 3- to 7-member cycloalkyl and 3- to 7-member heterocycloalkyl are independently optionally substituted by one, two or three Rs k R 12-1 , R 12-2 , R 12-4 and R 12-3 are independently C1-C3 alkyl, and the C1-C3 alkyl is independently optionally substituted by one, two or three Rs k-1 Each R k is independently halogen or C1-C3 alkyl Each R k-1 is independently halogen or C1-C3 alkyl The heteroatoms in the 3- to 7-member heterocycloalkyl, 4- to 6-member heterocycloalkyl and 5- to 12-member heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is one to three

[0683] In one embodiment, each R 1 is independently hydrogen, methyl

[0684]

Chemical formula

[0685] ethyl, chlorine,

[0686] [ka]

[0687] methoxy,

[0688] [ka]

[0689] isopropyl,

[0690] [ka]

[0691] ,amino,

[0692] [ka]

[0693] That is the case.

[0694] In one embodiment, each R 1 These are independently hydrogen, methyl,

[0695] [ka]

[0696] ethyl, chlorine,

[0697] [ka]

[0698] methoxy,

[0699] [ka]

[0700] isopropyl,

[0701] [ka]

[0702] , amino(-NH2),

[0703] [ka]

[0704] , trifluoromethyl,

[0705] [ka]

[0706] Alternatively, it is methylthio.

[0707] Preferably, each R 1 These are independently methyl,

[0708] [ka]

[0709] That is the case.

[0710] In one embodiment,

[0711] [ka]

[0712] teeth,

[0713] [ka] TIFF2026515254000207.tif243169TIFF2026515254000208.tif34169

[0714] And, Preferably,

[0715] [ka]

[0716] teeth,

[0717] [ka]

[0718] That is the case.

[0719] In one embodiment,

[0720] [ka]

[0721] teeth,

[0722] [ka] TIFF2026515254000213.tif242169 TIFF2026515254000214.tif251169 TIFF2026515254000215.tif33169

[0723] That is the case.

[0724] In one embodiment, L is -(CH2)-, -(CH2)2-,

[0725] [ka]

[0726] And preferably, L is

[0727] [ka]

[0728] And here,

[0729] [ka]

[0730] The symbol " indicates that it is connected to A.

[0731] Preferably, L is

[0732] [ka]

[0733] That is the case.

[0734] In one embodiment, L is -(CH2)-, -(CH2)2-,

[0735] [ka]

[0736] And preferably, L is

[0737] [ka]

[0738] And here,

[0739] [ka]

[0740] The symbol " indicates that it is connected to A.

[0741] In one embodiment, B is

[0742] [ka]

[0743] That is the case.

[0744] In one embodiment, B is

[0745] [ka]

[0746] That is the case.

[0747] Preferably, B is

[0748] [ka]

[0749] That is the case.

[0750] In one embodiment, B is

[0751] [ka]

[0752] That is the case.

[0753] In one embodiment, D is hydrogen, methyl,

[0754] [ka]

[0755] ethyl, isopropyl, cyclopropyl, trifluoromethyl or

[0756] [ka]

[0757] That is the case.

[0758] Preferably, D is

[0759] [ka]

[0760] That is the case.

[0761] In one embodiment, D is hydrogen, methyl,

[0762] [ka]

[0763] ethyl, isopropyl, cyclopropyl, trifluoromethyl or

[0764] [ka]

[0765] That is the case.

[0766] In one embodiment, the compound represented by formula I is one of the following compounds.

[0767] [ka] TIFF2026515254000233.tif224169 TIFF2026515254000234.tif199169 TIFF2026515254000235.tif200169 TIFF2026515254000236.tif248169 TIFF2026515254000237.tif211169 TIFF2026515254000238.tif182169 TIFF2026515254000239.tif240169 TIFF2026515254000240.tif155169

[0768] Preferably, the compound represented by formula I is

[0769] [ka]

[0770] That is the case.

[0771] The present invention further provides a method for preparing the compound represented by formula I described above, which is prepared by any of the following schemes.

[0772] Scheme (a): In an organic solvent, in the presence of a catalyst, the compound represented by formula II and the compound represented by formula III are subjected to the following condensation reaction to obtain the compound represented by formula I.

[0773] [ka]

[0774] Scheme (b): In an organic solvent, in the presence of a catalyst, the compound represented by formula IV and the compound represented by formula V are subjected to the following condensation reaction to obtain the compound represented by formula I.

[0775] [ka]

[0776] Scheme (C): In an organic solvent, in the presence of a catalyst, the compound represented by formula IV and the compound represented by formula VII are subjected to the following cyclization reaction to obtain the compound represented by formula I.

[0777] [ka]

[0778] Here, Z is a halogen (e.g., chlorine or bromine), TsO-, hydroxy, methoxy, ethoxy, n-propoxy, or isopropoxy, preferably Z is hydroxy, methoxy, ethoxy, n-propoxy, or isopropoxy. A, L, B, D, X1, X2, X3, X4, Y, and m are as described in any one of the claims of the present invention.

[0779] The present invention further provides a method for preparing the compound represented by formula I described above, which is prepared by any of the following schemes.

[0780] Scheme (D): In an organic solvent, in the presence of a catalyst, the compound represented by formula VIII and the compound represented by formula VIIII are subjected to the following cyclization reaction to obtain the compound represented by formula I.

[0781] [ka]

[0782] Here, Z, A, L, B, and D are as described in any one of the claims of the present invention.

[0783] The present invention further provides a pharmaceutical composition comprising a therapeutically effective amount of substance A and a pharmaceutical excipient, wherein substance A is a compound represented by the above formula I or a pharmaceutically acceptable salt thereof.

[0784] The present invention further provides the use of substance A in the preparation of a muscarinic receptor positive allosteric modulator, wherein substance A is a compound represented by formula I above, a pharmaceutically acceptable salt thereof, or the above pharmaceutical composition.

[0785] The present invention further provides the use of substance A in the preparation of a medicament used for the treatment and / or prevention of muscarinic receptor-mediated diseases, wherein substance A is a compound represented by formula I above or a pharmaceutically acceptable salt thereof, or the above medicament composition, and preferably the disease is Parkinson's disease, Alzheimer's disease, Huntington's disease, schizophrenia, drug addiction, or pain.

[0786] The present invention further provides the use of substance A in the preparation of pharmaceuticals used for the treatment of Parkinson's disease, Alzheimer's disease, Huntington's disease, schizophrenia, drug addiction, or pain.

[0787] Positive and progressive effects of the present invention: The compounds of the present invention can be used as muscarinic receptor positive allosteric modulators, and the compounds of the present invention can treat diseases mediated by (or related to) M receptors (muscarinic receptors).

[0788] Terminology Explanation: The term "-" indicates that this group is linked to the rest of the molecule through this site. For example, "CH3O-" refers to an alkoxy group.

[0789] term

[0790] [ka]

[0791] This indicates that this structural fragment is linked to the rest of the molecule through this site.

[0792] The term "pharmaceutically acceptable" refers to a substance that is relatively non-toxic, safe, and suitable for patient use.

[0793] The term "pharmaceutically acceptable salt" refers to a salt obtained by reacting a compound with a pharmaceutically acceptable acid or base. When a compound contains relatively acidic functional groups, a base addition salt can be obtained by contacting the compound with a sufficient amount of a pharmaceutically acceptable base in a suitable inert solvent. pharmaceutically acceptable base addition salts include lithium salts, sodium salts, potassium salts, calcium salts, aluminum salts, magnesium salts, zinc salts, bismuth salts, ammonium salts, and diethanolamine salts. When a compound contains relatively basic functional groups, an acid addition salt can be obtained by contacting the compound with a sufficient amount of a pharmaceutically acceptable acid in a suitable inert solvent. The pharmaceutically acceptable acids include inorganic acids and organic acids (e.g., trifluoroacetic acid, hydrochloric acid, formic acid). For specific examples, see Handbook of Pharmaceutical Salts: Properties, Selection, and Use (P. Heinrich Stahl, Camille G. Wermuth, 2011, 2nd Revised Edition), for example, formate salts.

[0794] The term "pharmaceutical excipients" refers to all substances contained in pharmaceutical preparations, excluding the active pharmaceutical ingredient, and is generally classified into two categories: excipients and additives. For specifics, refer to the "Pharmacopoeia of the People's Republic of China (2020 Edition)" and the "Handbook of Pharmaceutical Excipients" (Paul J Sheskey, Bruno C Hancock, Gary P Moss, David J Goldfarb, 2020, 9th Edition).

[0795] The term "treatment" refers to removing the cause of the disease or alleviating the symptoms.

[0796] The term "prevention" refers to reducing the risk of developing a disease.

[0797] The term "patient" refers to any animal that requires treatment or prevention of a disease, and is generally a mammal, such as a human. Mammals include, but are not limited to, cattle, horses, sheep, pigs, cats, dogs, mice, rats, rabbits, guinea pigs, monkeys, and humans.

[0798] The term "therapeutic dose" refers to the amount of compound administered to a patient that is sufficient to effectively treat a disease. The therapeutic dose varies depending on the type of compound, the type of disease, the severity of the disease, the patient's age, etc., but can be appropriately adjusted by those skilled in the art depending on the circumstances.

[0799] The expression "group B substituted by one or more groups A" refers to the substitution of one or more hydrogen atoms in group B by group A independently. When multiple groups A appear simultaneously, unless otherwise specified, their definitions are independent of each other and do not affect one another.

[0800] The term "halogen" refers to fluorine, chlorine, bromine, or iodine.

[0801] The term "oxo" refers to =O, where an oxygen atom replaces two hydrogen atoms on the same atom. For example, methylene (-(CH2-)) is oxygenated to become carbonyl (-C(=O)-).

[0802] The term "alkyl" refers to a linear or branched saturated monovalent hydrocarbon group having a specific number of carbon atoms. For example, C1-C6 alkyl(C 1-6 Alkyl) or C4~C 20 Alkyl (C 4-20 It is an alkyl group, preferably a C1-C4 alkyl group (C 1-4 Alkyl) or C9~C 15 Alkyl (C 9-15Alkyl is a alkyl group. Alkyl includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl.

[0803] In the term "alkyl-O-", the definition of alkyl is the same as above. Examples of alkyl-O- include C1-C6 alkyl-O- or C1-C4 alkyl-O-, and further, for example: CH3-O-, CH3CH2-O-, CH3CH2CH2-O-, or CH3CH(CH3)-O-. Similarly, for other "Rx-O-" expressions in this application, the definition of Rx is as described in the corresponding definitions, for example, the definition of cycloalkyl in "cycloalkyl-O-" is as described in "cycloalkyl" below.

[0804] In the term "alkyl-S-", the definition of alkyl is the same as above. Examples of alkyl-S- include C1-C6 alkyl-S- or C1-C4 alkyl-S-, and further, for example: CH3-S-, CH3CH2-S-, CH3CH2CH2-S-, or CH3CH(CH3)-S-. Similarly, for other "Rx-S-" expressions in this application, the definition of Rx is as described in the corresponding definitions, for example, the definition of cycloalkyl in "cycloalkyl-S-" is as described in "cycloalkyl" below.

[0805] The term "alkoxy" refers to a structure in which an oxygen atom is bonded to one end of an alkyl group as a connecting bond, forming an "alkyl-O-" molecule. Here, the definition of "alkyl-O-" is the same as above.

[0806] The term "alkylthio" refers to a structure in which a sulfur atom is bonded to one end of an alkyl group as a connecting bond, forming an "alkyl-S-" group. Here, the definition of "alkyl-S-" is the same as above.

[0807] The term "heteroaryl" refers to a cyclic, unsaturated monovalent group having a specific number of ring atoms (e.g., 5-12 members, 5-10 members, or 5-6 members), a specific number of heteroatoms (e.g., 1, 2, or 3), and a specific type of heteroatom (one or more of N, O, and S), and is aromatic.

[0808] The term "heterocycloalkyl" refers to saturated heterocycloalkyls or partially unsaturated monocyclic or polycyclic (e.g., bicyclic, tricyclic, or more bridging, condensed, or spirocyclic systems) heterocyclils having a specific number of ring atoms (e.g., 4-12 membered, 4-10 membered, 3-7 membered, 6-10 membered, 4-7 membered, or 5-6 membered), a specific number of heteroatoms (e.g., one, two, or three), and a specific type of heteroatom or heteroatomic group (one or more of N, O, S, S(=O), and S(=O)2).

[0809] The term "cycloalkyl" refers to a saturated carbon ring substituent that may be linked to the rest of the molecule by single bonds via any suitable carbon atom, and is a C3-C7 cycloalkyl having 3-7 carbon atoms, preferably a C3-C6 cycloalkyl having 3-6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0810] The term "aryl" refers to a specific number of carbon atoms (for example, C6-C6). 10 This refers to a cyclic, unsaturated monovalent hydrocarbon group having aryl compounds. Examples of aryl compounds include, but are not limited to, phenyl or naphthyl.

[0811] The term "heteroaryl" refers to a cyclic or unsaturated monovalent group having a specific number of carbon atoms (e.g., 5-10 membered, 5-6 membered), a specific number of heteroatoms (e.g., 1, 2, or 3), and a specific type of heteroatom (one or more of N, O, and S), which may be monocyclic or polycyclic and have aromaticity (at least one ring / each ring). Heteroaryls are linked to the rest of the molecule via carbon atoms or heteroatoms, heteroaryls are linked to the rest of the molecule via rings with or without heteroatoms, and heteroaryls are linked to the rest of the molecule via rings with or without aromaticity.

[0812] Unless otherwise explained, wedge-shaped solid line connections (

[0813] [ka]

[0814] ) and wedge-shaped dotted bond represent the absolute configuration of one stereocenter, and a wavy line between the atom and its substituent (

[0815] [ka]

[0816] When connected by ),

[0817] [ka]

[0818] It represents either a mixture thereof.

[0819] Based on the common sense of this field, each of the above preferred conditions can be arbitrarily combined to obtain each of the preferred examples of the present invention.

[0820] All reagents and raw materials used in this invention are commercially available.

[0821] Abbreviation: PMB: p-methoxybenzyl.

[0822] Boc:tert-butoxycarbonyl.

[0823] DBU:1,8-diazabicyclo[5.4.0]undeca-7-ene.

[0824] NBS: N-bromosuccinimide.

[0825] DIEA: N,N-diisopropylethylamine.

[0826] DMF: N,N-dimethylformamide.

[0827] Et: Ethyl.

[0828] Me: Methyl.

[0829] i-Pr: Isopropyl.

[0830] DMSO: Dimethyl sulfoxide.

[0831] HATU:O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate.

[0832] PyBOP: 1H-benzotriazole-1-yloxytripyrrolidinophosphonium hexafluorophosphate.

[0833] TEA: Triethylamine.

[0834] LiHMDS: Lithium bis(trimethylsilyl)amide.

[0835] NCS: N-chlorosuccinimide. [Modes for carrying out the invention]

[0836] The present invention will be further described below with reference to examples, but this does not limit the present invention to the scope of the above examples. Experimental methods for which specific conditions are not shown in the following examples can all be selected according to conventional methods and conditions, or according to the product's instructions.

[0837] Intermediate A Synthesis pathway:

[0838] [ka]

[0839] Step 1 A-1 (5.0 g, 20.5 mmol) was dissolved in dichloromethane (10 mL) and trifluoroacetic acid (10 mL), and the mixture was stirred at room temperature for 2 hours. After concentrating the reaction mixture under reduced pressure, the trifluoroacetic acid salt of A-2 was obtained. 1 H NMR (400 MHz, DMSO-d6) δ 4.13-3.91 (m, 4H), 3.83-3.66 (m, 2H), 3.11-3.03 (m, 1H), 2.74-2.63 (m, 2H), 1.19-1.13 (m, 3H). ESI-MS theoretical calculation value: C7H 14 NO2 [M+H] + = 144.1, measured value: 144.2.

[0840] Step 2 Trifluoroacetate of A-2 (5.0 g, 19.4 mmol) and A-3 (6.0 g, 33.5 mmol) were dissolved in dimethyl sulfoxide (10 mL), and triethylamine (13.4 g, 132.2 mmol) and cesium fluoride (5.0 g, 33.0 mmol) were added sequentially. The mixture was then heated to 80°C and stirred for 18 hours. The reaction mixture was poured into saturated ammonium chloride solution (20 mL), and dichloromethane (50 mL x 1) was added for extraction. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3 / 2, v / v) to obtain A-4. 1H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 5.64 Hz, 1H), 6.70 (d, J = 2.28 Hz, 1H), 6.53-6.48 (m, 1H), 4.17-4.04 (m, 4H), 3.70-3.67 (m, 2H), 3.10-3.01 (m, 1H), 2.76-2.72 (m, 2H), 1.21-1.17 (m, 3H). ESI-MS theoretical calculation value: C 13 H 16 F3N2O2[M+H] + = 289.1, measured value: 289.2.

[0841] Step 3 A-4 (1.0 g, 3.5 mmol) was dissolved in tetrahydrofuran (20 mL) and water (4 mL), and lithium hydroxide (0.22 g, 5.2 mmol) was added. The mixture was then stirred at room temperature for 2 hours. The pH of the reaction solution was adjusted to 7, water (50 mL) was added, and the mixture was freeze-dried to obtain a crude product containing intermediate A, which was used directly in the next step of the reaction. 1 H NMR (400 MHz, DMSO-d6) δ 8.25 (d, J = 5.64 Hz, 1H), 6.72 (d, J = 2.26 Hz, 1H), 6.55 (dd, J = 5.64, 2.26 Hz, 1H), 4.20-4.12 (m, 2H), 3.74-3.64 (m, 2H), 3.14-3.04 (m, 1H), 2.54-2.50 (m, 2H). ESI-MS theoretical calculation value: C 11 H 11 F3N2O2[M+H] + = 261.1, measured value: 261.0.

[0842] Intermediate B Synthesis pathway:

[0843] [ka]

[0844] Step 1 B-1 (5.0 g, 30.0 mmol) was dissolved in methanol (60 mL), triethylamine (12.5 mL, 90.0 mmol) and 1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (2.2 g, 3.0 mmol) were added, and the mixture was heated to 70°C and stirred for 12 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3 / 2, v / v) to obtain B-2. 1 H NMR (400 MHz, Chloroform-d) δ 7.36 (s, 1H), 4.09 (s, 3H), 2.70 (s, 3H), 2.63 (s, 3H). ESI-MS theoretical calculation value: C 10 H 11 N2O2[M+H] + = 191.1, measured value: 191.0.

[0845] Step 2 B-2 (4.5 g, 7.89 mmol) was dissolved in methanol (20 mL), and ranney nickel (930 mg, 15.8 mmol) was added. The reaction system was purged three times with hydrogen gas, and then the temperature was raised to 50°C and stirred for 12 hours. The reaction mixture was cooled to room temperature, filtered through diatomaceous earth, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 17 / 3, v / v) to obtain B-3. 1 HNMR (400 MHz, DMSO-d6) δ 8.82 (br, s, 1H), 7.25 (s, 1H), 4.31 (s, 2H), 2.52 (s, 3H), 2.32 (s, 3H). ESI-MS theoretical calculation value: C9H 11 N2O [M+H] + = 163.1, measured value: 163.2.

[0846] Step 3 B-3 (4.5 g, 27.8 mmol) was dissolved in tetrahydrofuran (50 mL), and tetrahydrofuran boranedimethyl sulfide complex (10 mol / L, 13.9 mL, 138.7 mmol) was added. The mixture was heated to 75°C and stirred for 12 hours. The reaction mixture was cooled to 0°C, quenched with methanol (200 mL), and hydrochloric acid (6 mol / L, 69.38 mL, 416.25 mmol) was added. The mixture was heated to 70°C and stirred for 3 hours. The reaction mixture was cooled to room temperature, the pH was adjusted to 9-10 with aqueous sodium hydroxide solution (2 mol / L), and di-tert-butyl dicarbonate (12.1 g, 55.5 mmol) was added. The mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, extracted with ethyl acetate (300 mL x 3), combined with the organic phase, dried over anhydrous sodium sulfate, and concentrated to obtain a crude product containing the target compound. This was then purified by silica gel column chromatography (dichloromethane / methanol, 17 / 3, v / v) to obtain B-4. 1 H NMR (400 MHz, Chloroform-d) δ 6.88 (s, 1H), 4.73-4.56 (m, 4H), 2.53 (s, 3H), 2.25 (s, 3H), 1.54 (s, 9H). ESI-MS theoretical calculation value: C 14 H 21 N2O2[M+H] + = 249.2, Measured value: 249.2.

[0847] Step 4 B-4 (5.0 g, 20.1 mmol) was dissolved in dichloromethane (10 mL), trifluoroacetic acid (10 mL) was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain the trifluoroacetate salt of intermediate B. 1 H NMR (400 MHz, DMSO-d6) δ 7.11 (s, 1H), 4.57-4.45 (m, 4H), 2.52 (s, 3H), 2.27 (s, 3H). ESI-MS theoretical calculation value: C9H 13 N2[M+H] + = 149.1, measured value: 149.1.

[0848] Intermediate C Synthesis pathway:

[0849] [ka]

[0850] Step 1 C-1 (10.0 g, 39.9 mmol) and C-2 (4.4 g, 46.6 mmol) were dissolved in methanol (32 mL) and water (128 mL), potassium carbonate (8.1 g, 58.3 mmol) was added, and the mixture was stirred at 60°C for 18 hours. The pH of the reaction mixture was adjusted to 7 with dilute hydrochloric acid (1 mol / L), and the mixture was extracted with dichloromethane (300 mL x 1). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. Petroleum ether (50 mL) was added, the mixture was stirred at room temperature for 30 minutes, and then filtered to obtain C-3. 1 H NMR (400 MHz, DMSO-d6) δ 4.38-4.26 (m, 4H), 2.37 (s, 3H), 1.44 (s, 9H). ESI-MS theoretical calculation value: C 12 H 18 N3O3[M+H] + = 252.1, measured value: 252.2.

[0851] Step 2 C-3 (2.0 g, 7.9 mmol) and C-4 (0.9 g, 15.9 mmol) were dissolved in DMF (10 mL), and DBU (2.4 g, 15.9 mmol) and PyBOP (6.2 g, 11.9 mmol) were added sequentially. The mixture was heated to 80°C and stirred for 18 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 1, v / v) to obtain C-5. 1 H NMR (400 MHz, DMSO-d6) δ 4.58-4.50 (m, 2H), 4.34-4.20 (m, 2H), 4.18-4.10 (m, 4H), 2.33 (s, 3H), 2.32-2.26 (m, 2H), 1.45 (s, 9H). Theoretical calculation value of ESI-MS: C 15 H23 N4O2[M+H] + = 291.2, Measured value: 291.2.

[0852] Step 3 C-5 (0.6 g, 2.1 mmol) was dissolved in dichloromethane (10 mL) and trifluoroacetic acid (10 mL), and the mixture was stirred at room temperature for 2 hours. After concentrating the reaction mixture under reduced pressure, the trifluoroacetate salt of intermediate C was obtained and used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 10 H 15 N4[M+H] + = 191.1, measured value: 191.2.

[0853] Intermediate D Synthesis pathway:

[0854] [ka]

[0855] Step 1 D-1 (1.0 g, 5.37 mmol), A-3 (970 mg, 5.37 mmol), cesium fluoride (820 mg, 5.37 mmol), and triethylamine (540 mg, 5.37 mmol) were added to DMSO (10 mL), and the mixture was heated to 100°C and stirred for 10 hours. The reaction mixture was diluted with water (30 mL), extracted with ethyl acetate (10 mL x 3), the organic phases were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (dichloromethane / methanol, 23 / 2, v / v) to obtain D-2. 1H NMR (400 MHz, Chloroform-d) δ 8.20 (d, J = 5.60 Hz, 1H), 6.50 (d, J = 2.30 Hz, 1H), 6.24 (dd, J = 5.70, 2.30 Hz, 1H), 4.76-4.70 (m, 1H), 4.02-3.95 (m, 2H), 3.68-3.61 (m, 2H), 3.39-3.32 (m, 2H), 2.97-2.87 (m, 1H), 1.38 (s, 9H). ESI-MS theoretical calculation value: C 15 H 21 F3N3O2[M+H] + = 332.2, measured value: 332.2.

[0856] Step 2 D-2 (1.1 g, 3.32 mmol) was dissolved in dichloromethane (10 mL) and trifluoroacetic acid (1.0 mL), and the mixture was stirred at 25°C for 16 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by high-performance liquid chromatography (chromatography column: Boston ODS C18 120 g Flash, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 25-50%, retention time: 6 min) to obtain intermediate D. Theoretical calculation value of ESI-MS: C 10 H 13 F3N3[M+H] + = 232.1, measured value: 232.0.

[0857] Intermediate E Synthesis pathway:

[0858] [ka]

[0859] Step 1 E-2 (910 mg, 10.5 mmol) and triethylamine (4.36 mL, 31.5 mmol) were dissolved in tetrahydrofuran (20 mL), cooled to 0°C, and then E-1 (2.0 g, 10.5 mmol) was added. The reaction system was slowly heated to room temperature and stirred for 12 hours. The reaction solution was diluted with water (50 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 7 / 3, v / v) to obtain E-3. 1 HNMR (400 MHz, DMSO-d6) δ 7.68 (d, J = 8.01 Hz, 2H), 7.42 (d, J = 8.10 Hz, 2H), 4.90 (d, J = 3.52 Hz, 1H), 4.17-4.12 (m, 1H), 3.27-3.13 (m, 2H), 3.00-2.96 (m, 1H), 2.40 (s, 3H), 1.72-1.67 (m, 1H), 1.66-1.56 (m, 1H). ESI-MS theoretical calculation value: C 11 H 16 NO3S [M+H] + = 242.1, measured value: 242.0.

[0860] Step 2 E-3 (1.2 g, 4.97 mmol) was dissolved in dichloromethane (12 mL), Dess-Martin reagent (2.5 g, 5.97 mmol) was added, and the mixture was stirred at room temperature for 6 hours. After filtering the reaction mixture, the filtrate was added to saturated sodium carbonate solution (50 mL), extracted with dichloromethane (40 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 7 / 3, v / v) to obtain E-4. 1H NMR (400 MHz, DMSO-d6) δ 7.68 (d, J = 8.01 Hz, 2H), 7.47 (d, J = 8.08 Hz, 2H), 3.49-3.43 (m, 4H), 2.45-2.39 (m, 5H). ESI-MS theoretical calculation value: C 11 H 14 NO3S [M+H] + = 240.1, measured value: 240.0.

[0861] Step 3 E-4 (700 mg, 2.93 mmol) was dissolved in tetrahydrofuran (10 mL), 3-bromopyridine (937 mg, 2.93 mmol) was added, and the mixture was stirred at room temperature for 4 hours. The reaction mixture was diluted with water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 4 / 1, v / v) to obtain E-5. 1 H NMR (400 MHz, DMSO-d6) δ 7.68 (d, J = 8.01 Hz, 2H), 7.48 (d, J = 8.08 Hz, 2H), 4.76-4.74 (m, 1H), 3.93-3.84 (m, 1H), 3.61-3.58 (m, 1H), 3.56-3.50 (m, 1H), 3.47-3.38 (m, 1H), 2.42 (s, 3H). Theoretical calculation value of ESI-MS: C 11 H 13 BrNO3S [M+H] + = 318.0, measured value: 317.8.

[0862] Step 4 E-5 (500 mg, 1.57 mmol) and E-6 (142 mg, 1.89 mmol) were dissolved in DMF (5 mL). The reaction system was heated to 60°C under the protection of nitrogen gas and stirred for 2 hours. After the reaction mixture was cooled to room temperature, it was diluted with water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing E-7, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 13 H 17 N2O3S2[M+H] + =313.1, measured value: 313.0.

[0863] Step 5 E-7 (450 mg, 1.44 mmol) and triethylamine (729 mg, 7.20 mmol) were dissolved in dichloromethane (5 mL), and methanesulfonyl chloride (330 mg, 2.88 mmol) was added dropwise, stirring at room temperature for 3 hours. The reaction mixture was quenched with water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain E-8, which was used directly in the next step of the reaction. 1 HNMR (400 MHz, DMSO-d6) δ 7.78 (d, J = 8.01 Hz, 2H), 7.43 (d, J = 8.07 Hz, 2H), 4.56 (dd, J = 4.31, 2.70 Hz, 2H), 4.43 (dd, J = 4.32, 2.70 Hz, 2H), 2.60 (s, 3H), 2.38 (s, 3H). ESI-MS theoretical calculation value: C 13 H 15 N2O2S2[M+H] + = 295.1, measured value: 295.0.

[0864] Step 6 E-8 (300 mg, 1.02 mmol) and phenol (96 mg, 1.02 mmol) were dissolved in an aqueous solution of hydrobromic acid (48%, 3 mL), and the mixture was heated to 90°C and stirred for 3 hours. After cooling to room temperature, the mixture was washed with ethyl acetate (10 mL x 3) to remove impurities, and the aqueous phase was concentrated to obtain the crude hydrobromic acid product containing intermediate E, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C6H9N2S [M+H] + = 141.0, Measured value: 141.0.

[0865] Intermediate F Synthesis pathway:

[0866] [ka]

[0867] Step 1 F-1 (1.0 g, 3.45 mmol), 1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (250 mg, 0.34 mmol), potassium carbonate (1.43 g, 10.34 mmol), F-2 (1.43 g, 10.34 mmol), and 1,4-dioxane (10 mL) were added to water (1 mL), and the mixture was heated to 80°C under nitrogen gas protection and stirred for 18 hours. After the reaction mixture was cooled to room temperature, it was filtered, the filtrate was diluted with water (30 mL), extracted with ethyl acetate (10 mL x 3), the organic phases were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 7 / 3, v / v) to obtain F-3. Theoretical calculation value of ESI-MS: C 13 H 20 N3O2[M+H] + = 250.2, Measured value: 250.2.

[0868] Step 2 F-3 (13.0 g, 37.42 mmol) was dissolved in dichloromethane (10 mL), trifluoroacetic acid (2 mL) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain the trifluoroacetate salt of intermediate F. Theoretical value calculated by ESI-MS: C8H 12 N3[M+H] + = 150.1, Measured value: 150.1.

[0869] intermediate G Synthesis pathway:

[0870] [ka]

[0871] Step 1 G-1 (2.0 g, 11.3 mmol), NBS (4.2 g, 23.7 mmol), and azobisisobutyronitrile (370 mg, 2.26 mmol) were sequentially added to carbon tetrachloride (25 mL). The reaction system was heated to 80°C under nitrogen gas protection and stirred for 16 hours. The reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure to obtain an oily substance. This oil was diluted with ethyl acetate (20 mL), washed with saturated sodium thiosulfate solution (15 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 9 / 1, v / v) to obtain G-2. Theoretical calculation value from ESI-MS: C6H5Br2Cl2N2[M+H] + = 332.8, measured value: 332.0.

[0872] Step 2 G-2 (4.00 g, 11.9 mmol) and potassium carbonate (4.9 g, 35.8 mmol) were added to tetrahydrofuran (4 mL), and a solution of 4-methoxybenzylamine in tetrahydrofuran (1.64 g, 11.9 mmol) was added dropwise at room temperature, followed by stirring at room temperature for 1 hour. The reaction mixture was filtered and concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 9 / 1, v / v) to obtain G-3. Theoretical calculation value of ESI-MS: C14 H 14 Cl2N3O [M+H] + = 310.0, Measured value: 310.0.

[0873] Step 3 G-3 (400 mg, 1.29 mmol), methylboronic acid (116 mg, 1.93 mmol), potassium carbonate (535 mg, 3.87 mmol), 1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (189 mg, 0.26 mmol), and 1,4-dioxane (3 mL) were added to a 10 mL microcentrifuge tube and heated to 90 °C under nitrogen gas protection, and stirred for 18 hours. The reaction mixture was cooled to room temperature, filtered, diluted with water (15 mL), extracted with ethyl acetate (5 mL x 3), the organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 9 / 1, v / v) to obtain G-4. Theoretical calculation value of ESI-MS: C 15 H 17 ClN3O [M+H] + = 290.1, Measured value: 290.0.

[0874] Step 4 G-4 (130 mg, 0.45 mmol) and azetidine (2 mL) were added to a 10 mL microcentrifuge tube, and the mixture was heated to 90°C and stirred for 16 hours. The reaction mixture was cooled to room temperature, diluted with water (15 mL), extracted with ethyl acetate (5 mL x 3), the organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 4 / 1, v / v) to obtain G-5. Theoretical calculation value of ESI-MS: C 18 H 23 N4O [M+H] + = 311.2, measured value: 311.2.

[0875] Step 5 G-5 (120 mg, 0.39 mmol) and trifluoroacetic acid (2 mL) were added to a 5 mL microcentrifuge tube, and the mixture was heated to 100°C and stirred for 8 hours. The reaction mixture was cooled to room temperature, diluted with water (15 mL), the pH was adjusted to 8 with saturated sodium bicarbonate solution, extracted with ethyl acetate (5 mL x 3), the organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain intermediate G, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 10 H 15 N4[M+H] + = 191.1, measured value: 191.1.

[0876] Intermediate H Synthesis pathway:

[0877] [ka]

[0878] Step 1 H-1 (1.0 g, 5.04 mmol), A-3 (920 mg, 5.04 mmol), cesium fluoride (0.77 g, 5.04 mmol), and triethyla (1.0 g, 10.1 mmol) were dissolved in DMSO (8 mL), heated to 100°C, and stirred for 18 hours. The reaction mixture was diluted with water (30 mL), extracted with ethyl acetate (10 mL x 3), the organic phases were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3 / 2, v / v) to obtain H-2. Theoretical calculation value of ESI-MS: C 16 H 21 F3N3O2[M+H] + = 344.2, measured value: 344.2.

[0879] Step 2 H-2 (600 mg, 1.75 mmol) was dissolved in trifluoroacetic acid (5 mL) and stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain the trifluoroacetate of intermediate H, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 11 H 13 F3N3[M+H] + = 244.1, measured value: 244.0.

[0880] Intermediate I Synthesis pathway:

[0881] [ka]

[0882] Step 1 G-3 (1.5 g, 4.84 mmol), 1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (710 mg, 0.97 mmol), potassium carbonate (2.0 g, 14.5 mmol), F-2 (1.21 g, 9.67 mmol), and 1,4-dioxane (10 mL) were heated to 90°C under nitrogen gas protection and stirred for 18 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 4 / 1, v / v) to obtain I-1. Theoretical calculation value of ESI-MS: C 16 H 20 N3O [M+H] + = 270.2, measured value: 270.1.

[0883] Step 2 I-1 (120 mg, 0.45 mmol) and trifluoroacetic acid (2 mL) were added to a 5 mL microcentrifuge tube, and the mixture was heated to 90°C and stirred for 8 hours. The reaction mixture was cooled to room temperature, concentrated under reduced pressure to obtain the trifluoroacetate containing intermediate I, and used directly in the next step of the reaction. Theoretical value calculated by ESI-MS: C8H 12 N3[M+H] + = 150.1, Measured value: 150.1.

[0884] Intermediate J Synthesis pathway:

[0885] [ka]

[0886] Step 1 J-1 (500 mg, 2.50 mmol) was added to water (3 mL), then concentrated hydrochloric acid (12 mol / L, 1 mL) was added, and after cooling to 0°C, sodium nitrite (223 mg, 3.23 mmol) was slowly added, and the mixture was stirred for 30 minutes while controlling the temperature of the reaction mixture to less than 5°C. Then potassium iodide (1.04 g, 6.22 mmol) was added, and the mixture was stirred at room temperature for 2 hours. Saturated sodium sulfite solution (10 mL) was added to the reaction mixture, diluted with water (15 mL), and then ethyl acetate (15 mL x 3) was added for extraction. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 1, v / v) to obtain J-2. 1 H NMR (400 MHz, DMSO-d6) δ 7.13 (s, 1H), 2.35 (s, 3H), 2.29 (s, 3H). ESI-MS theoretical calculation value: C7H8BrIN [M+H] + = 311.9, measured value: 311.8.

[0887] Step 2 J-2 (500 mg, 1.60 mmol), potassium carbonate (664 mg, 4.81 mmol), J-3 (790 mg, 4.10 mmol), and 1,4-dioxane (20 mL) were mixed with water (4 mL) and 1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (120 mg, 0.16 mmol) was added. The mixture was heated to 90°C under nitrogen gas protection and stirred for 18 hours. After the reaction was complete, the mixture was diluted with water (15 mL), extracted with ethyl acetate (15 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3 / 1, v / v) to obtain J-4. Theoretical calculation value of ESI-MS: C 15 H 22 NO2 [M+H] + = 248.2, Measured value: 248.2.

[0888] Step 3 J-4 (100 mg, 0.40 mmol) was dissolved in methanol (10 mL), moist palladium carbon (10%, 43 mg) was added, and the reaction system was purged three times with hydrogen gas. The mixture was then stirred at room temperature for 3 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain J-5. 1 H NMR (400 MHz, Chloroform-d) δ 6.80 (s, 1H), 3.76 (t, J = 7.42 Hz, 2H), 3.57-3.42 (m, 6H), 3.09 (t, J = 7.42 Hz, 2H), 2.96 (t, J = 6.94 Hz, 2H), 2.43 (s, 3H), 2.30 (s, 3H), 1.25-1.14 (m, 6H). ESI-MS theoretical calculation value: C 15 H 26 NO2 [M+H] + = 252.2, Measured value: 252.2.

[0889] Step 4 J-5 (300 mg, 1.19 mmol) was dissolved in a hydrobromic acid acetic acid solution (33% wt, 10 mL) and stirred at 60°C for 18 hours. The reaction solution was slowly poured into a saturated sodium carbonate solution, extracted with ethyl acetate (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3 / 1, v / v) to obtain J-6. 1 H NMR (400 MHz, DMSO-d6) δ 6.90 (s, 1H), 4.30 (t, J = 7.06 Hz, 2H), 4.04 (t, J = 7.36 Hz, 2H), 2.99 (t, J = 7.06 Hz, 2H), 2.88 (t, J = 7.36 Hz, 2H), 2.29 (s, 3H), 2.23 (s, 3H), 1.93 (s, 3H), 1.90 (s, 3H). ESI-MS theoretical calculation value: C 15 H 22 NO4 [M+H] + = 280.2, Measured value: 280.2.

[0890] Step 5 J-6 (100 mg, 0.36 mmol) was dissolved in methanol (5 mL), potassium carbonate (247 mg, 1.8 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing J-7, which was used directly in the next step. Theoretical calculation value by ESI-MS: C 11 H 18 NO2 [M+H] + = 196.3, measured value: 196.2.

[0891] Step 6 J-7 (50 mg, 0.26 mmol) was dissolved in dichloromethane (5 mL), and TEA (105 mg, 1.04 mmol) and p-toluenesulfonyl chloride (198 mg, 1.04 mmol) were added. The mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 4 / 1, v / v) to obtain J-8.1 H NMR (400 MHz, DMSO-d6) δ 7.61-7.52 (m, 4H), 7.38-7.26 (m, 4H), 6.74 (s, 1H), 4.32-4.25 (m, 2H), 4.05-3.97 (m, 2H), 2.85-2.76 (m, 4H), 2.34 (s, 3H), 2.32 (s, 3H), 2.15 (s, 3H), 2.05 (s, 3H). ESI-MS theoretical calculation value: C 25 H 30 NO6S2[M+H] + = 504.2, Measured value: 504.2.

[0892] Step 7 In a microwave reaction tube, J-8 (80 mg, 0.16 mmol) was dissolved in concentrated ammonia water (5 mL), and the reaction was carried out at 90°C for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain intermediate J, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 11 H 17 N2[M+H] + = 177.1, measured value: 177.2.

[0893] Intermediate K Synthesis pathway:

[0894] [ka]

[0895] Step 1 E-5 (900 mg, 2.83 mmol) and K-1 (292 mg, 2.83 mmol) were dissolved in DMF (10 mL). The reaction system was heated to 60°C under the protection of nitrogen gas and stirred for 2 hours. After the reaction mixture was cooled to room temperature, it was diluted with water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing K-2, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 15 H 21 N2O3S2[M+H]+ = 341.1, measured value: 341.0.

[0896] Step 2 K-2 (450 mg, 1.26 mmol) and triethyla (635 mg, 6.28 mmol) were dissolved in dichloromethane (5 mL), and methanesulfonyl chloride (287 mg, 2.51 mmol) was added dropwise, stirring at room temperature for 3 hours. The reaction mixture was quenched with water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product containing the target product. This was purified by silica gel column chromatography (dichloromethane / methanol, 9 / 1, v / v) to obtain K-3. Theoretical calculation value of ESI-MS: C 15 H 19 N2O2S2[M+H] + = 323.1, measured value: 323.1.

[0897] Step 3 K-3 (450 mg, 1.12 mmol) and phenol (131 mg, 1.12 mmol) were dissolved in an aqueous hydrobromic acid solution (48%, 5 mL), and the mixture was heated to 90°C and stirred for 3 hours. After cooling to room temperature, the mixture was washed with ethyl acetate (10 mL x 3) to remove impurities, and the aqueous phase was concentrated to obtain a crude hydrobromide salt product containing intermediate K, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C8H 13 N2S [M+H] + = 169.1, Measured value: 169.1.

[0898] Intermediate L Synthesis pathway:

[0899] [ka]

[0900] Step 1 E-5 (600 mg, 1.89 mmol) and L-1 (168 mg, 1.89 mmol) were dissolved in DMF (7 mL). The reaction system was heated to 60°C under the protection of nitrogen gas and stirred for 2 hours. After the reaction mixture was cooled to room temperature, it was diluted with water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing L-2, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 14 H 19 N2O3S2[M+H] + = 327.1, measured value: 327.0.

[0901] Step 2 L-2 (350 mg, 1.07 mmol) and triethylamine (543 mg, 5.36 mmol) were dissolved in dichloromethane (5 mL), and methanesulfonyl chloride (246 mg, 2.14 mmol) was added dropwise, stirring at room temperature for 3 hours. The reaction mixture was quenched with water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product containing the target product. This was purified by silica gel column chromatography (dichloromethane / methanol, 9 / 1, v / v) to obtain L-3. Theoretical calculation value of ESI-MS: C 14 H 17 N2O2S2[M+H] + = 309.1, measured value: 309.0.

[0902] Step 3 L-3 (300 mg, 0.88 mmol) and phenol (91.5 mg, 0.88 mmol) were dissolved in an aqueous hydrobromic acid solution (48%, 3 mL), and the mixture was heated to 90°C and stirred for 3 hours. After cooling to room temperature, the mixture was washed with ethyl acetate (10 mL x 3) to remove impurities, and the aqueous phase was concentrated to obtain a crude product containing the hydrobromide salt of intermediate L, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C7H 11 N2S [M+H] + = 155.1, measured value: 155.1.

[0903] Intermediate M Synthesis pathway:

[0904] [ka]

[0905] Step 1 Intermediate A (2.0 g, 7.69 mmol) was dissolved in tetrahydrofuran (10 mL), cooled to 0°C, and a solution of boranedimethyl sulfide in tetrahydrofuran (1 mol / L, 10 mL, 10 mmol) was added dropwise. The mixture was stirred at room temperature for 18 hours. The reaction system was quenched with methanol (5 mL), diluted with water (10 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target product. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 1, v / v) to obtain M-1. 1 H NMR (400 MHz, DMSO-d6) δ 8.20 (d, J = 5.64 Hz, 1H), 6.68 (d, J = 2.24 Hz, 1H), 6.50 (dd, J = 5.64, 2.26 Hz, 1H), 4.52-4.46 (m, 1H), 4.09 (t, J = 8.12 Hz, 2H), 3.67-3.61 (m, 2H), 3.47-3.41 (m, 2H), 2.90-2.79 (m, 1H), 1.80-1.72 (m, 2H). Step 2 Compound M-1 (1.0 g, 4.06 mmol) was dissolved in dichloromethane (5 mL), and p-toluenesulfonyl chloride (1.16 g, 6.09 mmol) and TEA (820 mg, 8.12 mmol) were added. The mixture was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was diluted with water (15 mL), extracted with dichloromethane (10 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 9 / 1, v / v) to obtain intermediate M. Theoretical calculation value of ESI-MS: C 18 H 20 F3N2O3S [M+H] + = 401.1, measured value: 401.1.

[0906] Intermediate N Synthesis pathway:

[0907] [ka]

[0908] Step 1 F-1 (6.0 g, 20.7 mmol) was dissolved in tetrahydrofuran (125 mL), iron(III) acetylacetonate (2.19 g, 6.20 mmol) was added, and the mixture was cooled to 0°C. Then, a tetrahydrofuran solution of methylmagnesium bromide (3 mol / L, 11 mL, 33.1 mmol) was added, and the mixture was stirred at room temperature for 18 hours. The reaction system was quenched with saturated ammonium chloride solution (50 mL), extracted with ethyl acetate (50 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target product. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 7 / 3, v / v) to obtain N-1. 1 H NMR (400 MHz, DMSO-d6) δ 4.66-4.53 (m, 4H), 2.43 (s, 3H), 1.50-1.45 (m, 9H). ESI-MS theoretical calculation value: C 12 H 17 ClN3O2[M+H]+ = 270.1, measured value: 270.1.

[0909] Step 2 N-1 (2.5 g, 9.27 mmol) was dissolved in methanol (100 mL), and 1,1'-bis(diphenylphosphin)ferrocene (520 mg, 0.93 mmol), TEA (3.75 g, 37.1 mmol), and palladium acetate (210 mg, 0.93 mmol) were added. The reaction system was substituted three times with carbon monoxide, and the temperature was raised to 70°C and stirred for 18 hours. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure, and purified by silica gel column chromatography (petroleum ether / ethyl acetate, 2 / 3, v / v) to obtain N-2. Theoretical calculation value of ESI-MS: C 14 H 20 N3O4[M+H] + =294.1, Measured value: 294.1.

[0910] Step 3 N-2 (1.9 g, 6.48 mmol) was dissolved in methanol (35 mL), sodium borohydride (490 mg, 12.9 mmol) was added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched with water (100 mL), extracted with dichloromethane (50 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 4, v / v) to obtain intermediate N. 1 H NMR (400 MHz, DMSO-d6) δ 4.63-4.54 (m, 6H), 2.41 (s, 3H), 1.47 (s, 9H). ESI-MS theoretical calculation value: C 13 H 20 N3O3[M+H] + = 266.1, Measured value: 266.1.

[0911] Intermediate O Synthesis pathway:

[0912] [ka]

[0913] Step 1 O-1 (2.0 g, 15.2 mmol) was dissolved in DMF (20 mL), and O-2 (1.52 g, 15.2 mmol) and sodium hydride (60%, 1.82 g, 45.6 mmol) were added sequentially. The mixture was heated to 60°C and stirred for 18 hours. After cooling, saturated ammonium chloride solution (50 mL) was slowly added to the reaction mixture, and the mixture was extracted with ethyl acetate (70 mL x 3). The organic phases were combined, washed with saturated brine (150 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 4 / 1, v / v) to obtain O-3. 1 H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 5.50 Hz, 1H), 7.26 (dd, J = 5.50, 1.76 Hz, 1H), 7.22 (d, J = 1.74 Hz, 1H), 5.09-4.96 (m, 2H). Step 2 O-3 (650 mg, 3.07 mmol) was dissolved in DMSO (6 mL), and intermediates A-2 (1.1 g, 3.07 mmol), TEA (1.86 g, 18.4 mmol), and cesium fluoride (700 mg, 4.02 mmol) were added sequentially. The mixture was heated to 100°C and stirred for 18 hours. After cooling, water (30 mL) was added to the reaction mixture, and it was extracted with dichloromethane (30 mL x 3). The organic phases were combined, washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel chromatography (petroleum ether / ethyl acetate, 4 / 1, v / v) to obtain O-4. 1H NMR (400 MHz, DMSO-d6) δ 7.76 (d, J = 5.76 Hz, 1H), 6.14 (dd, J = 5.80, 1.98 Hz, 1H), 5.77 (d, J = 1.96 Hz, 1H), 4.93-4.84 (m, 2H), 4.10-4.01 (m, 4H), 3.61-3.56 (m, 2H), 3.05-2.97 (m, 1H), 2.74-2.68 (m, 2H), 1.20-1.16 (m, 3H). ESI-MS theoretical calculation value: C 14 H 18 F3N2O3[M+H] + = 319.1, measured value: 319.1.

[0914] Step 3 O-4 (150 mg, 0.47 mmol) was dissolved in tetrahydrofuran (4 mL) and water (1 mL), lithium hydroxide (29 mg, 0.71 mmol) was added, and the mixture was heated to 60°C and stirred for 1 hour. After cooling, the pH of the reaction solution was adjusted to 7 with hydrochloric acid (1 mol / L), water was added, and the mixture was freeze-dried to obtain a crude product containing intermediate O, which was used directly in the next step of the reaction. 1 H NMR (400 MHz, DMSO-d6) δ 7.73 (d, J = 5.80 Hz, 1H), 6.10 (dd, J = 5.76, 1.98 Hz, 1H), 5.72 (d, J = 1.96 Hz, 1H), 4.92-4.84 (m, 2H), 4.01-3.96 (m, 2H), 3.54-3.50 (m, 2H), 2.98-2.88 (m, 1H), 2.35-2.32 (m, 2H). ESI-MS theoretical calculation value: C 12 H 14 F3N2O3[M+H] + = 291.1, measured value: 291.1.

[0915] Intermediate P Synthesis pathway:

[0916] [ka]

[0917] Step 1 P-1 (500 mg, 3.72 mmol) and A-2 (585 mg, 4.09 mmol) were dissolved in DMSO (5 mL), TEA (1.50 g, 14.90 mmol) and cesium fluoride (152 mg, 3.72 mmol) were added, and the mixture was heated to 100 °C and stirred for 18 hours. Saturated ammonium chloride solution (20 mL) was added to the reaction mixture, and the mixture was extracted with dichloromethane (20 mL x 3). The organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 1, v / v) to obtain P-2. 1 H NMR (400 MHz, Chloroform-d) δ 4.35-4.27 (m, 2H), 4.19-4.12 (m, 2H), 3.90-3.82 (m, 2H), 3.30-3.17 (m, 1H), 2.73 (d, J = 7.84 Hz, 2H), 2.42 (s, 3H), 1.26 (t, J = 7.78 Hz, 3H). ESI-MS theoretical calculation value: C 10 H 16 N3O2S [M+H] + = 242.1, measured value: 242.0.

[0918] Step 2 P-2 (200 mg, 0.83 mmol) was dissolved in methanol (2 mL) and water (1 mL), lithium hydroxide monohydrate (35 mg, 0.83 mmol) was added, and the mixture was stirred at room temperature for 3 hours. After the reaction was complete, the pH of the reaction solution was adjusted to 5 with dilute hydrochloric acid (1 mol / L), concentrated under reduced pressure, and then freeze-dried to obtain a crude product containing intermediate P, which was used directly in the next step of the reaction. 1 H NMR (400 MHz, Chloroform-d) δ 4.39-4.29 (m, 2H), 3.97-3.86 (m, 2H), 3.35-3.22 (m, 1H), 2.78 (d, J = 8.00 Hz, 2H), 2.44 (s, 3H). ESI-MS theoretical calculation value: C8H12 N3O2S [M+H] + = 214.1, measured value: 214.0.

[0919] Intermediate Q Synthesis pathway:

[0920] [ka]

[0921] Step 1 Q-2 (726 mg, 3.24 mmol) was dissolved in tetrahydrofuran (20 mL), cooled to 0°C, then sodium hydride (60%, 130 mg, 3.24 mmol) was added and the mixture was stirred for 1 hour. Q-1 (500 mg, 2.70 mmol) was then added and the mixture was stirred at room temperature for 18 hours. After the reaction was complete, the mixture was quenched with saturated ammonium chloride solution (5 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was then purified by silica gel column chromatography (petroleum ether / ethyl acetate, 4 / 1, v / v) to obtain Q-3. 1 H NMR (400 MHz, Chloroform-d) δ 5.69-5.63 (m, 1H), 5.06-5.01 (m, 0.3H), 4.81-4.76 (m, 0.7H), 4.68-4.50 (m, 2H), 4.15-4.03 (m, 2H), 1.40-1.36 (m, 12H), 1.24-1.15 (m, 3H). Step 2 Q-3 (500 mg, 1.96 mmol) was dissolved in methanol (10 mL), moist palladium carbon (10%, 450 mg) was added, and the reaction system was purged three times with hydrogen gas. The mixture was then stirred at room temperature for 1 hour. The reaction system was filtered, and the filtrate was concentrated under reduced pressure to obtain Q-4. 1H NMR (400 MHz, Chloroform-d) δ 4.47-4.35 (m, 0.6H), 4.13 (q, J = 7.14 Hz, 2H), 4.06-3.87 (m, 1.4H), 3.52-3.48 (m, 1H), 3.02-2.87 (m, 0.6H), 2.61-2.53 (m, 2H), 2.45-2.40 (m, 0.4H) 1.44 (s, 9H), 1.40 (d, J = 6.20 Hz, 1.2H), 1.27-1.23 (m, 4.8H). Step 3 Q-4 (250 mg, 0.97 mmol) was dissolved in dichloromethane (5 mL), trifluoroacetic acid (3 mL) was added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing Q-5, which was used directly in the next step. Theoretical calculation value by ESI-MS: C8H 16 NO2 [M+H] + = 158.1, Measured value: 158.1.

[0922] Step 4 Q-5 trifluoroacetate (140 mg, 0.89 mmol) and A-3 (173 mg, 0.95 mmol) were dissolved in dimethyl sulfoxide (5 mL), and TEA (385 mg, 3.80 mmol) and cesium fluoride (144 mg, 0.95 mmol) were added sequentially. The mixture was heated to 100°C and stirred for 18 hours. The reaction mixture was poured into water (20 mL), and dichloromethane (20 mL x 3) was added for extraction. The organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 2 / 3, v / v) to obtain Q-6. 1H NMR (400 MHz, DMSO-d6) δ 8.23-8.19 (m, 1H), 6.72 (s, 1H), 6.58 (d, J = 5.84 Hz, 1H), 4.53 (t, J = 7.24 Hz, 0.6H), 4.23-3.88 (m, 2.4H), 3.77-3.73 (m, 0.6H), 3.51-3.47 (m, 0.4H), 3.18-3.09 (m, 1H), 2.74-2.69 (m, 3H), 1.46 (d, J = 6.16 Hz, 1H), 1.31 (d, J = 6.52 Hz, 2H), 1.21-1.18 (m, 3H). Theoretical calculation value of ESI-MS: C 14 H 18 F3N2O2[M+H] + = 303.1, measured value: 303.1.

[0923] Step 5 Q-6 (180 mg, 0.57 mmol) was dissolved in tetrahydrofuran (4 mL) and water (1 mL), lithium hydroxide monohydrate (38 mg, 0.89 mmol) was added, and the mixture was stirred at room temperature for 3 hours. After the reaction was complete, the pH of the reaction solution was adjusted to 5 with dilute hydrochloric acid (1 mol / L), water was added, and the mixture was freeze-dried to obtain a crude product containing intermediate Q, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 12 H 14 F3N2O2[M+H] + = 275.1, measured value: 275.0.

[0924] Intermediate R Synthesis pathway:

[0925] [ka]

[0926] Step 1 R-1 (5.0 g, 17.5 mmol) and R-2 (1.82 g, 19.3 mmol) were dissolved in water (32 mL) and methanol (8 mL), potassium carbonate (3.63 g, 26.3 mmol) was added, and the mixture was heated to 60°C and stirred for 18 hours. The pH of the reaction solution was adjusted to 7 with dilute hydrochloric acid (1 mol / L), diluted with water (50 mL), extracted with dichloromethane (100 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. Petroleum ether (20 mL) was added and the mixture was stirred at room temperature for 30 minutes, then filtered to obtain R-3. 1 H NMR (400 MHz, DMSO-d6) δ 12.33 (br, 1H), 3.50-3.35 (m, 4H), 2.79-2.65 (m, 4H), 2.21 (s, 3H), 1.41 (s, 9H). ESI-MS theoretical calculation value: C 14 H 22 N3O3[M+H] + = 280.2, Measured value: 280.2.

[0927] Step 2 R-3 (1.0 g, 3.58 mmol) was dissolved in tetrahydrofuran (20 mL), cooled to 0°C, then sodium hydride (60%, 260 mg, 6.50 mmol) was added and the mixture was stirred for 30 minutes. R-4 (1.92 g, 5.37 mmol) was added, the temperature was raised to 25°C, and the mixture was stirred for 2 hours. After the reaction was complete, the pH was adjusted to 7 with dilute hydrochloric acid (1 mol / L), extracted with dichloromethane (50 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 9 / 1, v / v) to obtain R-5. Theoretical calculation value of ESI-MS: C 15 H 21 F3N3O5S [M-56+H] + = 356.1, measured value: 356.0.

[0928] Step 3 R-5 (500 mg, 1.22 mmol), cyclopropylboronic acid (208 mg, 2.43 mmol), potassium carbonate (504 mg, 3.65 mmol), and 1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (89 mg, 0.12 mmol) were added to 1,4-dioxane (15 mL) and water (5 mL). The reaction system was heated to 90°C under nitrogen gas protection and stirred for 18 hours. The reaction mixture was cooled to room temperature, filtered, diluted with water (15 mL), extracted with dichloromethane (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 4 / 1, v / v) to obtain R-6. Theoretical calculation value of ESI-MS: C 17 H 26 N3O2[M+H] + = 304.2, Measured value: 304.2.

[0929] Step 4 R-6 (260 mg, 0.86 mmol) was dissolved in dichloromethane (5 mL), trifluoroacetic acid (5 mL) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain the trifluoroacetate of intermediate R, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 12 H 18 N3[M+H] + = 204.1, measured value: 204.2.

[0930] Intermediate S Synthesis pathway:

[0931] [ka]

[0932] Step 1 S-2 (4.54 g, 61.3 mmol) was dissolved in tetrahydrofuran (120 mL), cooled to -78°C, and LiHMDS tetrahydrofuran solution (1.0 mol / L, 64.3 mL, 64.3 mmol) was slowly added dropwise, stirring for 10 minutes. Then S-1 (10 g, 58.4 mmol) was added and stirred for 15 minutes. The reaction system was heated to 0°C and stirred for 2 hours. Ice water (100 mL) was added, and the mixture was extracted with ethyl acetate (100 mL x 2). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing S-3, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 11 H 20 NO5 [M-56+H] + = 190.1, Measured value: 190.1.

[0933] Step 2 S-3 (2.0 g, 8.15 mmol) was dissolved in dichloromethane (20 mL), trifluoroacetic acid (20 mL) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain the trifluoroacetate of S-4, which was used directly in the next step. Theoretical value calculated by ESI-MS: C6H 12 NO3 [M+H] + = 146.1, measured value: 146.2.

[0934] Step 3 Trifluoroacetate of S-4 (2.0 g, 13.8 mmol) and A-3 (2.49 g, 13.8 mmol) were dissolved in dimethyl sulfoxide (10 mL), and TEA (5.58 g, 55.11 mmol) and cesium fluoride (2.1 g, 13.8 mmol) were added sequentially. The mixture was heated to 100 °C and stirred for 18 hours. The reaction mixture was poured into water (80 mL), and dichloromethane (50 mL x 3) was added for extraction. The organic phases were combined, washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3 / 7, v / v) to obtain S-5. 1H NMR (400 MHz, DMSO-d6) δ 8.22 (d, J = 5.68 Hz, 1H), 6.76 (d, J = 2.26 Hz, 1H), 6.62 -6.51 (m, 1H), 6.03 (s, 1H), 4.16-4.10 (m, 2H), 3.90-3.85 (m, 2H), 3.60 (s, 3H), 2.82 (s, 2H). ESI-MS theoretical calculation value: C 12 H 14 F3N2O3[M+H] + = 291.1, measured value: 291.1.

[0935] Step 4 S-5 (130 mg, 0.45 mmol) was dissolved in tetrahydrofuran (2 mL) and water (0.2 mL), lithium hydroxide monohydrate (28 mg, 0.68 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the pH of the reaction solution was adjusted to 5 with dilute hydrochloric acid (1 mol / L), water was added, and the mixture was freeze-dried to obtain a crude product containing intermediate S, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 11 H 12 F3N2O3[M+H] + = 277.1, measured value: 277.0.

[0936] Intermediate T Synthesis pathway:

[0937] [ka]

[0938] Step 1 T-1 (20g, 170.8 mmol) and T-2 (14.7g, 170.8 mmol) were dissolved in water (250 mL), cooled to 0°C, and sodium hydroxide aqueous solution (0.5 g / mL, 17.1 mL, 213 mmol) was added dropwise. The mixture was stirred at 0°C for 2 hours. After the reaction was complete, the mixture was filtered, and the solid was washed with water (20 mL x 3) to obtain T-3. Theoretical value calculated by ESI-MS: C7H 10 N3O2[M+H] += 168.1, Measured value: 168.0.

[0939] Step 2 At 0°C, T-3 (8.0 g, 47.9 mmol) was dissolved in phosphorus oxychloride (80 mL), and the mixture was heated to 105°C and stirred for 12 hours. After the reaction was complete, the mixture was concentrated under reduced pressure, dissolved in ethyl acetate (100 mL), poured into ice-cooled saturated sodium bicarbonate solution (200 mL), extracted with ethyl acetate (100 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3 / 1, v / v) to obtain T-4. 1 H NMR (400 MHz, DMSO-d6) δ 2.59 (s, 3H), 2.54 (s, 3H). Step 3 T-4 (3.50 g, 20.9 mmol) was dissolved in methanol (35 mL), and 1,1'-bis(diphenylphosphin)ferrocene (2.36 g, 4.18 mmol), TEA (6.34 g, 62.6 mmol), and palladium acetate (470 mg, 2.09 mmol) were added. The reaction system was substituted three times with carbon monoxide, and the temperature was raised to 70°C and stirred for 18 hours. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure, and purified by silica gel column chromatography (petroleum ether / ethyl acetate, 7 / 3, v / v) to obtain T-5. Theoretical value calculated by ESI-MS: C9H 10 N3O2[M+H] + = 192.1, measured value: 192.0.

[0940] Step 4 T-5 (1.20 g, 6.28 mmol) was dissolved in tetrahydrofuran (12 mL), cooled to 0°C, and lithium aluminum hydride tetrahydrofuran solution (1 mol / L, 15.7 mL, 15.7 mmol) was added dropwise. The mixture was stirred at 0°C for 2 hours. After the reaction was complete, water (3 mL) was added dropwise to the reaction solution, filtered, the filtrate was dried over anhydrous sodium sulfate, filtered again, and concentrated under reduced pressure to obtain a crude product containing T-6, which was used directly in the next step. Theoretical calculation value by ESI-MS: C8H14 N3O [M+H] + = 168.1, Measured value: 168.1.

[0941] Step 5 T-6 (800 mg, 4.78 mmol) and p-anisaldehyde (780 mg, 5.74 mmol) were dissolved in methanol (10 mL) and stirred at 25°C for 6 hours. Sodium borohydride (900 mg, 23.9 mmol) was then added, and the mixture was stirred for another 2 hours. Dilute hydrochloric acid (1 mol / L) was added dropwise to the reaction solution until the pH reached 6. The solution was diluted with water (20 mL), extracted with ethyl acetate (50 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. Purification by silica gel column chromatography (dichloromethane / methanol, 9 / 1, v / v) yielded T-7. Theoretical calculation value of ESI-MS: C 16 H 22 N3O2[M+H] + = 288.2, actual value: 288.1.

[0942] Step 6 T-7 (160 mg, 0.56 mmol) was dissolved in dichloromethane (2 mL), sulfonyl chloride (341 mg, 2.88 mmol) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing T-8. Theoretical calculation value by ESI-MS: C 16 H 21 ClN3O [M+H] + = 306.1, Measured value: 306.1.

[0943] Step 7 T-8 (140 mg, 0.46 mmol) was dissolved in tetrahydrofuran (2 mL), potassium carbonate (130 mg, 0.92 mmol) was added, and the mixture was heated to 60°C and stirred for 3 hours. The reaction mixture was filtered and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (dichloromethane / methanol, 23 / 2, v / v) to obtain T-9. Theoretical calculation value of ESI-MS: C 16 H 20 N3O [M+H]+ = 270.2, measured value: 270.1.

[0944] Step 8 In a 10 mL microcentrifuge tube, T-9 (25 mg, 0.09 mmol) was dissolved in trifluoroacetic acid (1 mL), and the mixture was heated to 80°C and stirred for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain the trifluoroacetate salt of the anti-intermediate T, which was used directly in the next step of the reaction. Theoretical value calculated by ESI-MS: C8H 12 N3[M+H] + = 150.1, Measured value: 150.1.

[0945] Intermediate U Synthesis pathway:

[0946] [ka]

[0947] Step 1 U-1 (1.0 g, 5.90 mmol) and manganese dioxide (6.66 g, 76.65 mmol) were added to dichloromethane (15 mL) and stirred at 25°C for 8 hours. The reaction mixture was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure to obtain U-2, which was used directly in the next step of the reaction. 1 H NMR (400 MHz, Chloroform-d) δ 8.74-8.66 (m, 1H), 7.51 (d, J = 5.06 Hz, 1H), 3.24-3.17 (m, 2H), 2.88-2.80 (m, 2H). ESI-MS theoretical calculation value: C8H7ClNO [M+H] + = 168.0, Measured value: 168.0.

[0948] Step 2 U-2 (1.1 g, 6.56 mmol) was dissolved in dichloromethane (15 mL), and diethylaminosulfur trifluoride (3.7 g, 22.97 mmol) was added at 0°C. The mixture was heated to room temperature and stirred for 18 hours. Saturated sodium bicarbonate solution (20 mL) was added to the reaction mixture, and the mixture was extracted with dichloromethane (20 mL x 1). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 7 / 3, v / v) to obtain U-3. 1 H NMR (400 MHz, Chloroform-d) δ 8.55 (d, J = 5.24 Hz, 1H), 7.39 (d, J = 5.22 Hz, 1H), 3.12-3.02 (m, 2H), 2.76-2.61 (m, 2H). ESI-MS theoretical calculation value: C8H7ClF2N [M+H] + = 190.0, Measured value: 190.0.

[0949] Step 3 Compounds U-3 (300 mg, 1.58 mmol) and A-2 (249 mg, 1.74 mmol) were dissolved in DMSO (10 mL), TEA (641 mg, 6.33 mmol) and cesium fluoride (240 mg, 1.58 mmol) were added, and the mixture was heated to 70°C and stirred for 18 hours. After the reaction mixture was cooled to room temperature, saturated ammonium chloride solution (50 mL) was added, and the mixture was extracted with ethyl acetate (40 mL x 3). The organic phases were combined, washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3 / 7, v / v) to obtain U-4. 1H NMR (400 MHz, Chloroform-d) δ 8.24 (d, J = 5.58 Hz, 1H), 6.15 (d, J = 5.60 Hz, 1H), 4.36-4.30 (m, 2H), 4.16 (q, J = 7.12 Hz, 2H), 3.88-3.81 (m, 2H), 3.20-3.09 (m, 1H), 3.03-2.96 (m, 2H), 2.71 (d, J = 7.78 Hz, 2H), 2.62-2.48 (m, 2H), 1.27 (t, J = 7.06 Hz, 3H). Theoretical calculation value of ESI-MS: C 15 H 19 F2N2O2[M+H] + = 297.1, measured value: 297.1.

[0950] Step 4 U-4 (70 mg, 0.24 mmol) was dissolved in tetrahydrofuran (2 mL) and water (0.4 mL), and lithium hydroxide monohydrate (10 mg, 0.24 mmol) was added. The mixture was stirred at room temperature for 3 hours. After the reaction was complete, the pH of the reaction solution was adjusted to 5 with dilute hydrochloric acid (1 mol / L), water was added, and the mixture was freeze-dried to obtain a crude product containing intermediate U, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 13 H 15 F2N2O2[M+H] + = 269.1, measured value: 269.1.

[0951] Intermediate V Synthesis pathway:

[0952] [ka]

[0953] Step 1 Compounds V-1 (100 mg, 0.55 mmol) and A-2 (157 mg, 0.55 mmol) were dissolved in DMSO (5 mL), TEA (221 mg, 2.19 mmol) and cesium fluoride (80 mg, 0.55 mmol) were added, and the mixture was heated to 100 °C and stirred for 18 hours. After the reaction mixture was cooled to room temperature, saturated ammonium chloride solution (20 mL) was added, and the mixture was extracted with ethyl acetate (15 mL x 3). The organic phases were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 2 / 3, v / v) to obtain V-2. 1 H NMR (400 MHz, Chloroform-d) δ 8.24 (d, J = 5.70 Hz, 1H), 6.23 (d, J = 5.86 Hz, 1H), 4.35-4.27 (m, 2H), 4.19-4.12 (m, 2H), 3.97-3.72 (m, 2H), 3.14-3.22 (m, 1H), 2.72 (d, J = 7.76 Hz, 2H), 1.28-1.24 (m, 3H). ESI-MS theoretical calculation value: C 12 H 15 F3N3O2[M+H] + = 290.3, measured value: 290.2.

[0954] Step 2 V-2 (80 mg, 0.28 mmol) was dissolved in tetrahydrofuran (2 mL) and water (0.4 mL), lithium hydroxide monohydrate (18 mg, 0.41 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the pH of the reaction solution was adjusted to 5 with dilute hydrochloric acid (1 mol / L), water was added, and the mixture was freeze-dried to obtain a crude product containing intermediate V, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 10 H 11 F3N3O2[M+H] + = 262.1, Measured value: 262.0.

[0955] Intermediate W Synthesis pathway:

[0956] [ka]

[0957] Step Q-2 (1.0 mg, 4.54 mmol) was dissolved in tetrahydrofuran (10 mL), cooled to 0°C, then sodium hydride (60%, 182 mg, 4.54 mmol) was added and the mixture was stirred for 1 hour. W-1 (800 mg, 3.79 mmol) was then added and the mixture was stirred at room temperature for 18 hours. After the reaction was complete, the mixture was quenched with saturated ammonium chloride solution (10 mL), extracted with ethyl acetate (30 mL x 3), the organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. W-2 was then purified by silica gel column chromatography (petroleum ether / ethyl acetate, 4 / 1, v / v). Theoretical calculation value of ESI-MS: C 15 H 24 NO4[M-56+H] + = 226.2, Measured value: 226.2.

[0958] Step 2 W-2 (300 mg, 1.07 mmol) was dissolved in ethanol (10 mL), and cobalt(II) chloride hexahydrate (26 mg, 0.11 mmol) and sodium borohydride (80 mg, 2.13 mmol) were added. The mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing W-3, which was used directly in the next step. Theoretical calculation value by ESI-MS: C 15 H 26 NO4[M-56+H] + = 228.2, Measured value: 228.2.

[0959] Step 3 W-3 (300 mg, 1.06 mmol) was dissolved in dichloromethane (5 mL), trifluoroacetic acid (3 mL) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing W-4, which was used directly in the next step. Theoretical calculation value by ESI-MS: C 10 H 18NO2 [M+H] + = 184.1, Measured value: 184.1.

[0960] Step 4 Trifluoroacetate of W-4 ​​(180 mg, 0.98 mmol) and A-3 (200 mg, 1.09 mmol) were dissolved in DMSO (10 mL), TEA (442 mg, 4.37 mmol) and cesium fluoride (166 mg, 1.09 mmol) were added, and the mixture was heated to 100°C and stirred for 10 hours. After the reaction mixture was cooled to room temperature, saturated ammonium chloride solution (20 mL) was added, and the mixture was extracted with dichloromethane (15 mL x 3). The organic phases were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 1, v / v) to obtain W-5. 1 H NMR (400 MHz, Chloroform-d) δ 8.24 (d, J = 5.70 Hz, 1H), 6.23 (d, J = 5.86 Hz, 1H), 4.35-4.27 (m, 2H), 4.19-4.12 (m, 2H), 3.97-3.72 (m, 2H), 3.14-3.22 (m, 1H), 2.72 (d, J = 7.76 Hz, 2H), 1.28-1.24 (m, 3H). ESI-MS theoretical calculation value: C 16 H 20 F3N2O2[M+H] + = 329.1, measured value: 329.2.

[0961] Step 5 W-5 (50 mg, 0.15 mmol) was dissolved in tetrahydrofuran (2 mL) and water (0.4 mL), lithium hydroxide monohydrate (10 mg, 0.23 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the pH of the reaction solution was adjusted to 5 with dilute hydrochloric acid (1 mol / L), water was added, and the mixture was freeze-dried to obtain a crude product containing intermediate W, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 14 H 16 F3N2O2[M+H] += 301.1, measured value: 301.1.

[0962] Intermediate X Synthesis pathway:

[0963] [ka]

[0964] Step 1 X-1 (900 mg, 4.68 mmol) was dissolved in 1,4-dioxane (40 mL), X-2 (1.8 g, 5.61 mmol) was added, and the mixture was heated to 90°C and stirred for 18 hours. After the reaction mixture was cooled to room temperature, it was diluted with water (50 mL), extracted with ethyl acetate (50 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 0, v / v) to obtain X-3. 1 H NMR (400 MHz, Chloroform-d) δ 8.52 (d, J = 5.34 Hz, 1H), 7.58 (d, J = 1.82 Hz, 1H), 7.32 (dd, J = 5.30, 1.84 Hz, 1H). Step 2 X-3 (100 mg, 0.47 mmol) and A-2 (201 mg, 0.70 mmol) were dissolved in DMSO (3 mL), TEA (142 mg, 1.40 mmol) and cesium fluoride (71 mg, 0.47 mmol) were added, and the mixture was heated to 100°C and stirred for 18 hours. After the reaction mixture was cooled to room temperature, saturated ammonium chloride solution (10 mL) was added, and the mixture was extracted with dichloromethane (15 mL x 3). The organic phases were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 7 / 3, v / v) to obtain X-4. Theoretical calculation value of ESI-MS: C 13 H 14 F3N2O2S [M+H] += 321.1, measured value: 321.1.

[0965] Step 3 X-4 (150 mg, 2.50 mmol) was dissolved in tetrahydrofuran (3 mL) and water (1 mL), lithium hydroxide monohydrate (30 mg, 0.70 mmol) was added, and the mixture was heated to 40°C and stirred for 2 hours. After the reaction was complete, the pH of the reaction solution was adjusted to 5 with dilute hydrochloric acid (1 mol / L), water was added, and the mixture was freeze-dried to obtain a crude product containing intermediate X, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 11 H 12 F3N2O2S[M+H] + = 293.1, Measured value: 293.1.

[0966] Intermediate Y Synthesis pathway:

[0967] [ka]

[0968] Step 1 F-1 (3.0 g, 10.3 mmol) was dissolved in methanol (10 mL), cooled to 0°C, sodium methoxide (630 mg, 11.4 mmol) was added, and the mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with water (20 mL), extracted with dichloromethane (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3 / 2, v / v) to obtain Y-1. 1 H NMR (400 MHz, Chloroform-d) δ 4.68-4.52 (m, 4H), 4.06 (s, 3H), 1.52 (s, 9H). ESI-MS theoretical calculation value: C 12 H 17 ClN3O3[M+H] + = 286.1, measured value: 286.0.

[0969] Step 2 Y-1 (1.6 g, 5.60 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane complex (460 mg, 0.56 mmol), potassium carbonate (2.32 g, 16.8 mmol), F-2 (1.41 g, 11.20 mmol), and 1,4-dioxane (10 mL) and water (1 mL) were heated to 90°C under the protection of nitrogen gas and stirred for 18 hours. The reaction mixture was cooled to room temperature, filtered, diluted with water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 4, v / v) to obtain Y-2. 1 H NMR (400 MHz, Chloroform-d) δ 4.68-4.49 (m, 4H), 4.02 (s, 3H), 2.65 (s, 3H), 1.51 (s, 9H). ESI-MS theoretical calculation value: C 13 H 20 N3O3[M+H] + = 266.1, Measured value: 266.1.

[0970] Step 3 Y-2 (1.1 g, 4.15 mmol) was dissolved in dichloromethane (10 mL), trifluoroacetate (10 mL) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain trifluoroacetate of intermediate Y. Theoretical value calculated by ESI-MS: C8H 12 N3O[M+H] + = 166.1, Measured value: 166.1.

[0971] Intermediate Z Synthesis pathway:

[0972] [ka]

[0973] Step 1 Z-1 (500 mg, 2.48 mmol) and Z-2 (340 mg, 2.73 mmol) were dissolved in ethanol (10 mL), and the mixture was heated to 80°C and stirred for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by silica gel column chromatography (dichloromethane / methanol, 9 / 1, v / v) to obtain Z-3. Theoretical calculation value of ESI-MS: C 11 H 20 N3O2[M+H] + = 226.1, measured value: 226.1.

[0974] Step 2 Under the protection of nitrogen gas, oxalyl chloride (197 mg, 1.55 mmol) was dissolved in dichloromethane (1 mL), cooled to -78°C, and DMSO (303 mg, 3.88 mmol) was slowly added dropwise, and the mixture was stirred at -78°C for 30 minutes. Z-3 (347 mg, 1.54 mmol) was dissolved in dichloromethane (1 mL), slowly added to the above reaction mixture, stirred for 15 minutes, and then DIEA (502 mg, 3.88 mmol) was added dropwise, the temperature was raised to room temperature, and the mixture was stirred for 3 hours. The reaction mixture was diluted with dichloromethane (30 mL), washed with saturated ammonium chloride solution (5 mL), the organic phase was washed with saturated brine (10 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain intermediate Z. Theoretical calculation value by ESI-MS: C 11 H 18 N3O2[M+H] + =224.1, measured value: 224.2.

[0975] Intermediate AA Synthesis pathway:

[0976] [ka]

[0977] Step 1 AA-1 (1.4 g, 12.2 mmol) was dissolved in DMF (30 mL), cooled to 0°C, then sodium hydride (60%, 910 mg, 22.8 mmol) was added and the mixture was stirred for 30 minutes. O-1 (2.0 g, 15.2 mmol) was then added and the mixture was stirred at room temperature for 18 hours. After the reaction was complete, the mixture was quenched with saturated ammonium chloride solution (150 mL), extracted with ethyl acetate (150 mL x 3), the organic phases were combined, washed with saturated brine (300 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was then purified by silica gel column chromatography (petroleum ether / ethyl acetate, 19 / 1, v / v) to obtain AA-2. 1 H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 5.50 Hz, 1H), 7.25 (dd, J = 5.54, 1.78 Hz, 1H), 7.16 (d, J = 1.80 Hz, 1H), 5.95-5.86 (m, 1H), 1.45 (d, J = 6.68 Hz, 3H). Step 2 AA-2 (400 mg, 1.77 mmol) and A-2 (254 mg, 1.77 mmol) were dissolved in DMSO (15 mL), TEA (1.08 g, 10.6 mmol) and cesium fluoride (404 mg, 2.66 mmol) were added, and the mixture was heated to 100 °C and stirred for 10 hours. After the reaction mixture was cooled to room temperature, saturated ammonium chloride solution (50 mL) was added, and the mixture was extracted with ethyl acetate (50 mL x 3). The organic phases were combined, washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3 / 17, v / v) to obtain AA-3. 1H NMR (400 MHz, Chloroform-d) δ 7.75 (d, J = 5.74 Hz, 1H), 6.12 (dd, J = 5.82, 1.98 Hz, 1H), 5.87-5.80 (m, 1H), 5.73 (d, J = 1.96 Hz, 1H), 4.10-4.01 (m, 4H), 3.62-3.54 (m, 2H), 3.07-2.97 (m, 1H), 2.70 (d, J = 7.70 Hz, 2H), 1.38 (d, J = 6.54 Hz, 3H), 1.18 (t, J = 7.10 Hz, 3H). ESI-MS theoretical calculation value: C 15 H 20 F3N2O3[M+H] + = 333.1, measured value: 333.1.

[0978] Step 3 AA-3 (350 mg, 1.05 mmol) was dissolved in tetrahydrofuran (2 mL) and water (0.4 mL), lithium hydroxide monohydrate (66 mg, 1.58 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the pH of the reaction solution was adjusted to 5 with dilute hydrochloric acid (1 mol / L), filtered, the solid was washed with water (3 mL), and dried to obtain intermediate AA, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 13 H 16 F3N2O3[M+H] + =305.1, Measured value: 305.1.

[0979] Intermediate AB Synthesis pathway:

[0980] [ka]

[0981] Step 1 AB-1 (208 mg, 1.82 mmol) was dissolved in DMF (4 mL), cooled to 0°C, then sodium hydride (60%, 137 mg, 3.43 mmol) was added and the mixture was stirred for 30 minutes. O-1 (300 mg, 2.28 mmol) was then added and the mixture was stirred at room temperature for 18 hours. After the reaction was complete, the mixture was quenched with saturated ammonium chloride solution (30 mL), extracted with ethyl acetate (30 mL x 3), the organic phases were combined, washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was then purified by silica gel column chromatography (petroleum ether / ethyl acetate, 19 / 1, v / v) to obtain AB-2. 1 H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 5.50 Hz, 1H), 7.25 (dd, J = 5.58, 1.76 Hz, 1H), 7.16 (d, J = 1.74 Hz, 1H), 5.93-5.85 (m, 1H), 1.45 (d, J = 6.68 Hz, 3H). Step 2 AB-2 (200 mg, 0.89 mmol) and A-2 (317 mg, 2.22 mmol) were dissolved in DMSO (5 mL), TEA (538 mg, 5.32 mmol) and cesium fluoride (202 mg, 1.33 mmol) were added, and the mixture was heated to 100°C and stirred for 10 hours. After the reaction mixture was cooled to room temperature, saturated ammonium chloride solution (20 mL) was added, and the mixture was extracted with ethyl acetate (20 mL x 3). The organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3 / 17, v / v) to obtain AB-3. Theoretical calculation value of ESI-MS: C 15 H 20 F3N2O3[M+H] + = 333.1, measured value: 333.0.

[0982] Step 3 AB-3 (100 mg, 0.30 mmol) was dissolved in tetrahydrofuran (2 mL) and water (0.4 mL), lithium hydroxide monohydrate (10 mg, 0.45 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the pH of the reaction solution was adjusted to 5 with dilute hydrochloric acid (1 mol / L), filtered, the solid was washed with water (3 mL), and dried to obtain intermediate AB, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 13 H 16 F3N2O3[M+H] + = 305.1, measured value: 305.0.

[0983] intermediate AC Synthesis pathway:

[0984] [ka]

[0985] Step 1 Intermediate C (1.06 g, 5.57 mmol) and intermediate AC-1 (1.20 g, 5.57 mmol) were dissolved in DMF (50 mL), DIEA (4.32 g, 3.5 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Then HATU (2.54 g, 6.69 mmol) was added, and the mixture was stirred at room temperature for 1 hour. After the reaction was complete, the mixture was diluted with water (100 mL), extracted with ethyl acetate (80 mL x 3), the organic phases were combined, washed with saturated brine (150 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (dichloromethane / methanol, 5 / 1, v / v) to obtain AC-2. Theoretical calculation value of ESI-MS: C 20 H 30 N5O3[M+H] + = 388.2, measured value: 388.3.

[0986] Step 2 AC-2 (2.00 g, 5.16 mmol) was dissolved in dichloromethane (15 mL), trifluoroacetic acid (15 mL) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing intermediate AC, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 15 H 22 N5O [M+H] + = 288.2, measured value: 288.1.

[0987] Intermediate AD Synthesis pathway:

[0988] [ka]

[0989] Step 1 AD-1 (1.90 g, 16.5 mmol) and A-3 (2.00 g, 11.0 mmol) were dissolved in DMSO (30 mL), TEA (4.46 g, 44.1 mmol) and cesium fluoride (1.67 g, 11.0 mmol) were added, and the mixture was heated to 80°C and stirred for 12 hours. After the reaction mixture was cooled to room temperature, it was diluted with water (150 mL), extracted with ethyl acetate (100 mL x 3), the organic phases were combined, washed with saturated brine (200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 9 / 1, v / v) to obtain AD-2. Theoretical calculation value of ESI-MS: C 11 H 12 F3N2O2[M+H] + = 260.1, Measured value: 260.1.

[0990] Step 2 AD-2 (1.61 g, 6.15 mmol) was dissolved in tetrahydrofuran (20 mL), and a tetrahydrofuran solution of lithium aluminum hydride (1.0 mol / L, 12.3 mL, 12.3 mmol) was added at 0°C, and the mixture was stirred for 2 hours. After the reaction was complete, the reaction system was quenched with ice water (40 mL), extracted with ethyl acetate (40 mL x 3), the organic phases were combined, washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (dichloromethane / methanol, 19 / 1, v / v) to obtain AD-3. 1 H NMR (400 MHz, DMSO-d6) δ 8.20 (d, J = 5.68 Hz, 1H), 6.68 (d, J = 2.28 Hz, 1H), 6.51 (dd, J = 5.70, 2.24 Hz, 1H), 4.85-4.81 (m, 1H), 4.00 (t, J = 8.22 Hz, 2H), 3.75-3.70 (m, 2H), 3.57 (t, J = 5.72 Hz, 2H), 2.91-2.82 (m, 1H). ESI-MS theoretical calculation value: C 10 H 12 F3N2O [M+H] + = 233.1, measured value: 233.0.

[0991] Step 3 AD-3 (200 mg, 0.86 mmol) and TEA (261 mg, 2.58 mmol) were dissolved in dichloromethane (10 mL), and methanesulfonyl chloride (148 mg, 1.29 mmol) was added at 0°C. The mixture was stirred for 2 hours. After the reaction was complete, the reaction system was quenched with water (10 mL), extracted with dichloromethane (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain AD-4, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 11 H 14 F3N2O3S [M+H] + = 311.1, measured value: 311.0.

[0992] Step 4 AD-4 (300 mg, 0.97 mmol) was dissolved in DMF (5 mL), potassium thioacetate (334 mg, 2.90 mmol) and 18-crown-6-ether (767 mg, 2.90 mmol) were added, and the mixture was heated to 40°C and stirred for 4 hours. The reaction mixture was cooled to room temperature, diluted with water (25 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 17 / 3, v / v) to obtain AD-5. 1 H NMR (400 MHz, Chloroform-d) δ 8.28 (d, J = 5.66 Hz, 1H), 6.57 (d, J = 2.32 Hz, 1H), 6.32 (dd, J = 5.66, 2.34 Hz, 1H), 4.12-4.06 (m, 2H), 3.71-3.62 (m, 2H), 3.20 (d, J = 7.34 Hz, 2H), 3.10-2.99 (m, 1H), 2.38 (s, 3H). ESI-MS theoretical calculation value: C 12 H 14 F3N2OS [M+H] + = 291.1, measured value: 291.0.

[0993] Step 5 AD-5 (170 mg, 0.59 mmol) was dissolved in acetonitrile (5 mL), NCS (236 mg, 1.77 mmol) was added, and hydrochloric acid (1.0 mol / L, 0.5 mL) was added dropwise at 0°C, and the mixture was stirred for 3 hours. The reaction system was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing intermediate AD, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 10 H 11 ClF3N2O2S[M+H] + =315.0, Measured value: 315.0.

[0994] Intermediate AE Synthesis pathway:

[0995] [ka]

[0996] Step 1 AE-1 (40g, 140 mmol) was dissolved in DMF (400 mL), potassium carbonate (38.7 g, 280 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Then, ethyl bromo (35.1 g, 210 mmol) was added, and the mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with water (500 mL), extracted with ethyl acetate (500 mL x 3), the organic phases were combined, washed with saturated brine (800 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 4 / 1, v / v) to obtain AE-2. Theoretical calculation value of ESI-MS: C 18 H 29 NNaO7[M+Na] + =394.2, Measured value: 394.2.

[0997] Step 2 AE-2 (38 g, 102 mmol) was dissolved in tetrahydrofuran (150 mL) and water (150 mL), and sodium hydroxide (23.3 g, 582 mmol) was slowly added. The mixture was stirred at room temperature for 18 hours. The reaction mixture was extracted with dichloromethane (50 mL), the aqueous phase was adjusted to pH 3 with hydrochloric acid (3 mol / L), extracted with dichloromethane (150 mL x 3), the organic phase was combined, washed with saturated brine (200 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing AE-3, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 13 H 21 NNaO5[M+H] + =294.1, Measured value: 294.1.

[0998] Step 3 AE-3 (14 g, 51.6 mmol) was dissolved in tetrahydrofuran (100 mL), cooled to 0°C, and acetic acid (55.1 g, 918 mmol) and hydrazine hydrate (98%, 2.58 g, 51.6 mmol) were added. The mixture was heated to 80°C and stirred for 18 hours. The reaction mixture was cooled to room temperature, the pH was adjusted to 8 with saturated sodium bicarbonate solution, extracted with dichloromethane (150 mL x 3), the organic phases were combined, washed with saturated brine (200 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing AE-4, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 13 H 22 N3O3[M+H] + = 268.2, measured value: 268.1.

[0999] Step 4 AE-4 (7.0 g, 26.2 mmol) was dissolved in toluene (70 mL), manganese dioxide (18.2 g, 209 mmol) was added, and the mixture was heated to 110°C and stirred for 12 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (dichloromethane / methanol, 9 / 1, v / v) to obtain AE-5. Theoretical calculation value of ESI-MS: C 13 H 20 N3O3[M+H] + = 266.1, measured value: 266.2.

[1000] Step 5 AE-5 (1.0 g, 3.77 mmol) was dissolved in phosphorus oxychloride (10 mL), and the mixture was heated to 100°C and stirred for 8 hours. The reaction mixture was cooled to room temperature, concentrated under reduced pressure to obtain an oily substance, dissolved in tetrahydrofuran (10 mL) and water (2 mL), potassium carbonate (2.6 g, 18.9 mmol) and di-tert-butyl dicarbonate (2.5 g, 11.3 mmol) were added, and the mixture was stirred at room temperature for 12 hours. The reaction mixture was diluted with water (15 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 1, v / v) to obtain AE-6. Theoretical calculation value of ESI-MS: C 13 H 20 N3O3[M+H] + = 266.1, measured value: 266.2.

[1001] Step 6 AE-6 (200 mg, 0.77 mmol), methylboronic acid (84 mg, 1.40 mmol), potassium carbonate (292 mg, 2.11 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (46 mg, 0.07 mmol) were added to 1,4-dioxane (5 mL) and water (1 mL). The mixture was heated to 100°C under nitrogen gas protection and stirred for 18 hours. The reaction mixture was cooled to room temperature, diluted with water (10 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, washed with saturated brine (40 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 1, v / v) to obtain AE-7. Theoretical calculation value of ESI-MS: C 14 H 22 N3O2[M+H] + = 264.2, measured value: 264.1.

[1002] Step 7 AE-7 (150 mg, 0.57 mmol) was dissolved in 1,4-dioxane (5 mL), and a 1,4-dioxane solution in hydrochloric acid (4 mol / L, 0.43 mL, 1.71 mmol) was added. The mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the intermediate AE, which was used directly in the next step. Theoretical calculation value by ESI-MS: C9H 14 N3[M+H] + = 164.1, Measured value: 164.1.

[1003] Intermediate AF Synthesis pathway:

[1004] [ka]

[1005] Step 1 AF-1 (5.0 g, 30.0 mmol) and A-2 (4.3 g, 30.0 mmol) were dissolved in DMSO (60 mL), TEA (18.2 g, 180 mmol) and cesium fluoride (6.8 g, 44.9 mmol) were added, and the mixture was heated to 60°C and stirred for 5 hours. After the reaction mixture was cooled to room temperature, it was diluted with water (300 mL), extracted with ethyl acetate (250 mL x 3), the organic phases were combined, washed with saturated brine (500 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 1, v / v) to obtain AF-2. Theoretical calculation value of ESI-MS: C 11 H 14 ClFN3O2[M+H] + =274.1, measured value: 274.0.

[1006] Step 2 AF-2 (3.0 g, 11.0 mmol), cyclopropylboronic acid (1.9 g, 21.9 mmol), potassium carbonate (4.5 g, 32.9 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (800 mg, 1.10 mmol) were added to 1,4-dioxane (10 mL) and water (2 mL). The mixture was heated to 90°C under nitrogen gas protection and stirred for 18 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 2 / 3, v / v) to obtain AF-3. Theoretical calculation value of ESI-MS: C 14 H 19 FN3O2[M+H] + = 280.1, measured value: 280.2.

[1007] Step 3 AF-3 (500 mg, 1.79 mmol) was dissolved in tetrahydrofuran (10 mL) and water (2 mL), lithium hydroxide monohydrate (113 mg, 2.69 mmol) was added, and the mixture was stirred at 40°C for 5 hours. After the reaction was complete, the pH of the reaction solution was adjusted to 5 with dilute hydrochloric acid (1 mol / L), filtered, the solid was washed with water (3 mL), and dried to obtain intermediate AF, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 12 H 15 FN3O2[M+H] + = 252.1, measured value: 252.2.

[1008] Intermediate AG Synthesis pathway:

[1009] [ka]

[1010] Step 1 R-5 (500 mg, 1.22 mmol), 1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (99 mg, 0.12 mmol), potassium carbonate (504 mg, 3.65 mmol), and F-2 (305 mg, 2.43 mmol) were added to 1,4-dioxane (10 mL) and water (1 mL), and the mixture was heated to 90°C under the protection of nitrogen gas and stirred for 18 hours. The reaction mixture was cooled to room temperature, diluted with water (30 mL), extracted with ethyl acetate (15 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 2 / 3, v / v) to obtain AG-1. 1 H NMR (400 MHz, DMSO-d6) δ 3.54-3.47 (m, 4H), 2.99-2.95 (m, 2H), 2.88-2.84 (m, 2H), 2.46 (s, 3H), 2.41 (s, 3H), 1.37 (s, 9H). Theoretical calculation value of ESI-MS: C 15 H 24 N3O2[M+H] + = 278.2, Measured value: 278.2.

[1011] Step 2 AG-1 (230 mg, 0.83 mmol) was dissolved in dichloromethane (4 mL), trifluoroacetate (4 mL) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain the trifluoroacetate of intermediate AG, which was used directly in the next step. Theoretical calculation value by ESI-MS: C 10 H 16 N3[M+H] + = 178.1, Measured value: 178.1.

[1012] Intermediate AH Synthesis pathway:

[1013] [ka]

[1014] Step 1 C-3 (2.0 g, 4.78 mmol) was dissolved in tetrahydrofuran (40 mL), cooled to 0°C, sodium hydride (60%, 480 mg, 12.0 mmol) was added, and the mixture was stirred for 30 minutes. R-4 (5.12 g, 14.3 mmol) was added, the temperature was raised to 25°C, and the mixture was stirred for 18 hours. After the reaction was complete, the mixture was diluted with saturated ammonium chloride solution (100 mL), extracted with ethyl acetate (80 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 1, v / v) to obtain AH-1. Theoretical calculation value of ESI-MS: C 13 H 17 F3N3O5S[M+H] + =384.1, measured value: 384.2.

[1015] Step 2 AH-1 (2.0 g, 5.22 mmol), cyclopropylboronic acid (900 mg, 10.4 mmol), potassium carbonate (2.16 g, 15.7 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (380 mg, 0.52 mmol) were added to 1,4-dioxane (20 mL) and water (5 mL). The reaction mixture was heated to 90°C under nitrogen gas protection and stirred for 18 hours. The reaction mixture was cooled to room temperature, filtered, diluted with water (30 mL), extracted with ethyl acetate (30 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 7 / 3, v / v) to obtain AH-2. Theoretical calculation value of ESI-MS: C 15 H 22 N3O2[M+H] + = 276.2, measured value: 276.1.

[1016] Step 3 AH-2 (600 mg, 2.18 mmol) was dissolved in dichloromethane (4 mL), trifluoroacetate (4 mL) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain the trifluoroacetate of intermediate AH, which was used directly in the next step. Theoretical calculation value by ESI-MS: C 10 H 14 N3[M+H] + = 176.1, Measured value: 176.1.

[1017] Intermediate AI Synthesis pathway:

[1018] [ka]

[1019] Step 1 Q-5 (109 mg, 0.69 mmol) and P-1 (112 mg, 0.83 mmol) were dissolved in DMSO (5 mL), TEA (280 mg, 2.77 mmol) and cesium fluoride (105 mg, 0.69 mmol) were added, and the mixture was heated to 70°C and stirred for 18 hours. Saturated ammonium chloride solution (20 mL) was added to the reaction mixture, extracted with ethyl acetate (20 mL x 3), the organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 4 / 1, v / v) to obtain AI-1. Theoretical calculation value of ESI-MS: C 11 H 18 N3O2S [M+H] + = 256.1, Measured value: 256.1.

[1020] Step 2 AI-1 (90 mg, 0.35 mmol) was dissolved in tetrahydrofuran (2 mL) and water (1 mL), and lithium hydroxide monohydrate (18 mg, 0.42 mmol) was added. The mixture was stirred at room temperature for 3 hours. After the reaction was complete, the pH of the reaction solution was adjusted to 5 with dilute hydrochloric acid (1 mol / L), concentrated under reduced pressure, and then freeze-dried to obtain a crude product containing the intermediate AI, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C9H 14 N3O2S [M+H] + = 228.1, measured value: 228.0.

[1021] Intermediate AJ Synthesis pathway:

[1022] [ka]

[1023] Step 1 O-3 (1.0, 5.16 mmol) was dissolved in DMSO (20 mL), and intermediates AJ-1 (1.1 g, 5.16 mmol), TEA (1.86 g, 18.4 mmol), and cesium fluoride (1.18 g, 7.75 mmol) were added sequentially. The mixture was heated to 100°C and stirred for 18 hours. After cooling, water (100 mL) was added to the reaction mixture, and it was extracted with dichloromethane (100 mL x 3). The organic phases were combined, washed with saturated brine (300 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 7 / 3, v / v) to obtain AJ-2. Theoretical calculation value of ESI-MS: C 15 H 20 F3N2O3[M+H] + =333.1, measured value: 333.2.

[1024] Step 2 AJ-2 (700 mg, 2.11 mmol) was dissolved in tetrahydrofuran (20 mL) and water (5 mL), lithium hydroxide (133 mg, 3.16 mmol) was added, and the mixture was stirred at 25°C for 2 hours. After the reaction was complete, the pH of the reaction solution was adjusted to 6 with hydrochloric acid (1 mol / L), water was added, and the mixture was freeze-dried to obtain a crude product containing intermediate AJ, which was used directly in the next step of the reaction. 1 H NMR (400 MHz, DMSO-d6) δ 7.74 (d, J = 6.02Hz, 1H), 6.26 (d, J = 6.06 Hz, 1H), 5.84 (s, 1H), 4.93-4.86 (m, 2H), 3.50-3.45 (m, 2H), 3.30-3.20 (m, 2H), 2.95-2.88 (m, 1H), 2.37-2.30 (m, 2H), 2.12 (s, 1H), 1.70-1.60 (m, 1H). ESI-MS theoretical calculation value: C 13 H 16 F3N2O3[M+H] + = 305.1, measured value: 305.2.

[1025] Intermediate AK Synthesis pathway:

[1026] [ka]

[1027] Step 1 G-4 (500 mg, 1.73 mmol), cyclopropylboronic acid (296 mg, 3.45 mmol), potassium carbonate (596 mg, 4.31 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (253 mg, 0.35 mmol) were added to 1,4-dioxane (6 mL), and the mixture was heated to 100°C under the protection of nitrogen gas and stirred for 12 hours. The reaction mixture was cooled to room temperature, filtered, diluted with water (30 mL), extracted with ethyl acetate (30 mL x 3), the organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 2 / 3, v / v) to obtain AK-1. 1 HNMR(400MHz,DMSO-d6)δ7.30 (d, J = 8.60 Hz, 2H), 6.92 (d, J = 8.62 Hz, 2H), 4.03-4.00 (m, 2H), 3.91-3.88 (m, 2H), 3.85 (s, 2H), 3.75 (s, 3H), 2.44 (s, 3H), 1.99-1.95 (m, 1H), 1.12-1.08 (m, 2H), 1.00-0.95 (m, 2H). ESI-MS theoretical calculation value: C 18 H 22 N3O [M+H] + = 296.2, measured value: 296.1.

[1028] Step 2 AK-1 (300 mg, 1.02 mmol) and trifluoroacetate (4 mL) were added to a microcentrifuge tube, and the mixture was heated to 90°C and stirred for 10 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to obtain trifluoroacetate containing the intermediate AK, which was then used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 10 H 14 N3[M+H] + = 176.1, measured value: 176.0.

[1029] Intermediate AL Synthesis pathway:

[1030] [ka]

[1031] Step 1 F-1 (3.0 g, 10.3 mmol) was dissolved in tetrahydrofuran (30 mL), iron(III) acetylacetonate (1.1 g, 3.10 mmol) was added, the mixture was cooled to 0°C, and then a solution of ethylmagnesium bromide in tetrahydrofuran (1.0 mol / L, 19.4 mL, 19.4 mmol) was added. The mixture was stirred at room temperature for 18 hours. The reaction system was quenched with saturated ammonium chloride solution (50 mL), extracted with ethyl acetate (50 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 1, v / v) to obtain AL-1. Theoretical value calculated by ESI-MS: C14H21ClN3O2 [M+H]+ = 298.1, experimental value: 298.2.

[1032] Step 2 AL-1 (1.70 g, 5.99 mmol), methylboronic acid (720 mg, 12.0 mmol), potassium carbonate (2.48 g, 18.0 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (440 mg, 0.66 mmol) were added to 1,4-dioxane (20 mL) and water (5 mL). The mixture was heated to 90°C under nitrogen gas protection and stirred for 18 hours. The reaction mixture was cooled to room temperature, filtered, diluted with water (100 mL), extracted with ethyl acetate (100 mL x 3), the organic phases were combined, washed with saturated brine (200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 1, v / v) to obtain AL-2. Theoretical calculation value of ESI-MS: C 14 H 22 N3O2[M+H] + = 264.2, measured value: 264.3.

[1033] Step 3 AL-2 (380 mg, 1.44 mmol) was dissolved in dichloromethane (4 mL), trifluoroacetate (2 mL) was added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to obtain the trifluoroacetate of the intermediate AL, which was used directly in the next step. Theoretical value calculated by ESI-MS: C9H 14 N3[M+H] + = 164.1, Measured value: 164.1.

[1034] Intermediate AM Synthesis pathway:

[1035] [ka]

[1036] Step 1 C-1 (20.0 g, 77.7 mmol) and AM-1 (10.1 g, 93.3 mmol) were dissolved in water (32 mL) and methanol (128 mL), potassium carbonate (16.1 g, 117 mmol) was added, and the mixture was heated to 60°C and stirred for 18 hours. The pH of the reaction mixture was adjusted to 5-6 with dilute hydrochloric acid (1 mol / L), concentrated under reduced pressure, diluted with water (100 mL), extracted with dichloromethane (100 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure to obtain a crude product containing the target compound, petroleum ether (20 mL) was added and stirred at room temperature for 30 minutes, then filtered to obtain AM-2. Theoretical calculation value by ESI-MS: C 19 H 20 N3O3[M+H] + = 266.1, measured value: 266.2.

[1037] Step 2 AM-2 (3.0 g, 11.3 mmol) was dissolved in tetrahydrofuran (30 mL), cooled to 0°C, then sodium hydride (60%, 810 mg, 33.9 mmol) was added and the mixture was stirred for 30 minutes. R-4 (10.1 g, 28.3 mmol) was added, the temperature was raised to 25°C, and the mixture was stirred for 18 hours. After the reaction was complete, the mixture was diluted with saturated ammonium chloride solution (100 mL), extracted with ethyl acetate (80 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 1, v / v) to obtain AM-3. Theoretical calculation value of ESI-MS: C 14 H 19 F3N3O5S[M+H] + =398.1, Measured value: 398.1.

[1038] Step 3 AM-3 (1.0 g, 2.52 mmol), 1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (210 mg, 0.25 mmol), potassium carbonate (1.04 g, 7.55 mmol), and F-2 (630 mg, 5.03 mmol) were added to 1,4-dioxane (10 mL) and water (1 mL), and the mixture was heated to 90°C under nitrogen gas protection and stirred for 18 hours. The reaction mixture was cooled to room temperature, diluted with water (50 mL), extracted with ethyl acetate (50 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 4, v / v) to obtain AM-4. Theoretical calculation value of ESI-MS: C 14 H 22 N3O2[M+H] + = 264.2, Measured value: 264.2.

[1039] Step 4 AM-4 (200 mg, 0.76 mmol) was added to dichloromethane (4 mL), trifluoroacetate (2 mL) was added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to obtain trifluoroacetate of intermediate AM, which was used directly in the next step of the reaction. Theoretical value calculated by ESI-MS: C9H 14 N3[M+H] + = 164.1, measured value: 164.2.

[1040] Intermediate AN Synthesis pathway:

[1041] [ka]

[1042] Step 1 F-1 (1.0 g, 3.45 mmol) was dissolved in tetrahydrofuran (10 mL), cooled to 0°C, and sodium methyl mercaptan (270 mg, 3.79 mmol) was added. The mixture was stirred at room temperature for 2 hours. The reaction system was quenched with saturated ammonium chloride solution (50 mL), extracted with dichloromethane (50 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3 / 2, v / v) to obtain AN-1. Theoretical calculation value of ESI-MS: C 12 H 16 35 ClN3O2S[M+H] + =302.1, measured value: 302.0.

[1043] Step 2 AN-1 (900 mg, 2.98 mmol), 1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (240 mg, 0.30 mmol), potassium carbonate (1.24 g, 8.95 mmol), and F-2 (748 mg, 5.96 mmol) were added to 1,4-dioxane (10 mL) and water (1 mL), and the mixture was heated to 90°C under nitrogen gas protection and stirred for 18 hours. The reaction mixture was cooled to room temperature, diluted with water (50 mL), extracted with ethyl acetate (50 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 4, v / v) to obtain AN-2. Theoretical calculation value of ESI-MS: C 13 H 20 N3O2S[M+H] + = 282.1, Measured value: 282.1.

[1044] Step 3 AN-2 (500 mg, 1.78 mmol) was dissolved in dichloromethane (4 mL), trifluoroacetate (4 mL) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain the trifluoroacetate of the intermediate AN, which was used directly in the next step. Theoretical value calculated by ESI-MS: C8H 12 N3S[M+H] + = 182.1, measured value: 182.2.

[1045] Intermediate AO Synthesis pathway:

[1046] [ka]

[1047] Step 1 G-4 (200 mg, 0.69 mmol), methanesulfonate (tricyclohexylphosphine) (2'-amino-1,1'-biphenyl-2-yl)palladium(II) (45 mg, 0.07 mmol), potassium phosphate (513 mg, 2.42 mmol), and ethylboronic acid (153 mg, 2.07 mmol) were added to toluene (5 mL) and water (1 mL), and the mixture was heated to 100 °C under the protection of nitrogen gas and stirred for 12 hours. The reaction mixture was cooled to room temperature, diluted with water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 2 / 3, v / v) to obtain AO-1. 1 H NMR (400 MHz, DMSO-d6) δ 7.29 (d, J = 8.54 Hz, 2H), 6.92 (d, J = 8.52 Hz, 2H), 3.96-3.85 (m, 6H), 3.75 (s, 3H), 2.80 (q, J = 7.58 Hz, 2H), 2.47 (s, 3H), 1.20 (t, J = 7.58 Hz, 3H). ESI-MS theoretical calculation value: C 17 H 22 N3O [M+H] + = 284.2, measured value: 284.1.

[1048] Step 2 AO-1 (150 mg, 0.53 mmol) and trifluoroacetic acid (4 mL) were added to a microcentrifuge tube, and the mixture was heated to 90°C and stirred for 10 hours. The reaction mixture was cooled to room temperature, concentrated under reduced pressure to obtain the trifluoroacetate containing the intermediate AO, which was used directly in the next step of the reaction. Theoretical value calculated by ESI-MS: C9H 14 N3[M+H] + = 164.1, measured value: 164.0.

[1049] Intermediate AP Synthesis pathway:

[1050] [ka]

[1051] Step 1 G-3 (200 mg, 0.64 mmol), methanesulfonate (tricyclohexylphosphine) (2'-amino-1,1'-biphenyl-2-yl)palladium(II) (42 mg, 0.06 mmol), potassium phosphate (479 mg, 2.26 mmol), and ethylboronic acid (285 mg, 3.87 mmol) were added to toluene (5 mL) and water (1 mL), and the mixture was heated to 100 °C under the protection of nitrogen gas and stirred for 18 hours. The reaction mixture was cooled to room temperature, diluted with water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (dichloromethane / methanol, 9 / 1, v / v) to obtain AP-1. 1 H NMR (400 MHz, DMSO-d6) δ 7.31 (d, J = 8.60 Hz, 2H), 6.91 (d, J = 8.62 Hz, 2H), 3.95 (s, 3H), 3.85 (s, 2H), 3.75 (s, 4H), 2.80 (q, J = 7.58 Hz, 4H), 1.21 (t, J = 7.60 Hz, 6H). ESI-MS theoretical calculation value: C 18 H 24 N3O [M+H] + = 298.2, measured value: 298.1.

[1052] Step 2 AP-1 (150 mg, 0.50 mmol) and trifluoroacetic acid (4 mL) were added to a microcentrifuge tube, and the mixture was heated to 90°C and stirred for 10 hours. The reaction mixture was cooled to room temperature, concentrated under reduced pressure to obtain a trifluoroacetate containing the intermediate AP, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 10 H 16 N3[M+H] + = 178.1, measured value: 178.0.

[1053] Intermediate AQ Synthesis pathway:

[1054] [ka]

[1055] Step 1 AQ-1 (5.0 g, 38.3 mmol) and pyridine (3.51 g, 44.4 mmol) were dissolved in acetonitrile (100 mL), and trifluoromethanesulfonic acid anhydride (12.1 g, 42.9 mmol) was slowly added at 0°C. The mixture was stirred at 25°C for 30 minutes, sodium iodide (28.7 g, 191.5 mmol) was added, and then trifluoromethanesulfonic acid (6.32 g, 42.1 mmol) was slowly added. The mixture was then stirred at 25°C for 3 hours. Water (50 mL) was added to the reaction mixture, and the pH was adjusted to 10 with sodium hydroxide solution (1 mol / L). Subsequently, 10% sodium carbonate solution (50 mL) and saturated sodium thiosulfate solution (100 mL) were added, and the mixture was extracted with ethyl acetate (200 mL x 3). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was then purified by silica gel column chromatography (petroleum ether / ethyl acetate, 9 / 1, v / v) to obtain AQ-2. 1 H NMR (400 MHz, DMSO-d6) δ 9.41 (d, J = 2.24 Hz, 1H), 8.54 (d, J = 2.26 Hz, 1H). ESI-MS theoretical calculation value: C4H3ClIN2[M+H] + = 240.9, measured value: 241.0.

[1056] Step 2 After mixing copper iodide (1.48 g, 7.78 mmol) and potassium fluoride (450 mg, 7.78 mmol), the mixture was evacuated using an oil pump and shaken while being sprayed with a heat gun. When the mixture turned a deep yellowish-green color, heating was stopped and the bottle was immediately sealed with a rubber stopper. AQ-2 (1.70 g, 7.07 mmol) was dissolved in DMF (20 mL), and N-methylpyrrolidone (7.96 g, 80.3 mmol) and (trifluoromethyl)trimethylsilane (1.11 g, 7.78 mmol) were added. The compounds were quickly injected into the bottle using a syringe and stirred at 25°C for 12 hours. After the reaction was complete, saturated ammonium chloride solution (100 mL) was added to the reaction mixture to quench it, extracted with ethyl acetate (100 mL x 3), washed with saturated sodium bicarbonate (250 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was then purified by silica gel column chromatography (petroleum ether / ethyl acetate, 4 / 1, v / v) to obtain AQ-3. 1 H NMR (400 MHz, Chloroform-d) δ 9.40 (d, J = 2.26 Hz, 1H), 7.89 (d, J = 2.30 Hz, 1H). Step 3 A-2 (86 mg, 0.62 mmol) and AQ-3 (100 mg, 0.55 mmol) were dissolved in dimethyl sulfoxide (5 mL), and triethylamine (222 mg, 2.19 mmol) and cesium fluoride (83 mg, 0.55 mmol) were added sequentially. The mixture was then heated to 70°C and stirred for 18 hours. The reaction mixture was poured into saturated ammonium chloride solution (50 mL), and ethyl acetate (50 mL x 1) was added for extraction. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3 / 7, v / v) to obtain AQ-4. Theoretical calculation value of ESI-MS: C 12 H 15 F3N3O2[M+H] + = 290.1, Measured value: 290.1.

[1057] Step 4 AQ-4 (87 mg, 0.30 mmol) was dissolved in tetrahydrofuran (4 mL) and water (1 mL), and lithium hydroxide monohydrate (15 mg, 0.36 mmol) was added. The mixture was then stirred at room temperature for 2 hours. The pH of the reaction mixture was adjusted to 6, water (50 mL) was added, and the mixture was freeze-dried to obtain a crude product containing intermediate AQ, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 10 H 11 F3N3O2[M+H] + = 262.1, Measured value: 262.0.

[1058] Intermediate AR Synthesis pathway:

[1059] [ka]

[1060] Step 1 Intermediate I (800 mg, 5.36 mmol) and intermediate AC-1 (1.15 g, 5.36 mmol) were dissolved in DMF (10 mL), DIEA (2.08 g, 16.1 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Then HATU (3.06 g, 8.04 mmol) was added, and the mixture was stirred at room temperature for 1 hour. After the reaction was complete, the mixture was diluted with water (100 mL), extracted with ethyl acetate (80 mL x 3), the organic phases were combined, washed with saturated brine (150 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (dichloromethane / methanol, 4 / 1, v / v) to obtain AR-1. Theoretical calculation value of ESI-MS: C 18 H 27 N4O3[M+H] + = 347.3, measured value: 347.2.

[1061] Step 2 AR-1 (1.00 g, 2.89 mmol) was dissolved in dichloromethane (6 mL), trifluoroacetic acid (2 mL) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the intermediate AR, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 13 H 19 N4O [M+H] + = 247.2, measured value: 247.1.

[1062] Product preparation and synthesis

[1063] [ka]

[1064] Step 1 Intermediate C trifluoroacetate (200 mg, 1.1 mmol) and intermediate A (274 mg, 1.1 mmol) were dissolved in DMF (5 mL), DIEA (0.41 g, 3.2 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Then HATU (0.6 g, 1.6 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, and preparative HPLC (chromatography: XBridge® Prep C18 OBD) was performed. TM Compound 1 was obtained by purification using a 10 μm, 19 × 250 mm (mobile phase: acetonitrile-water, gradient: 0-48%, retention time: 9 min) sample. 1 H NMR (400 MHz, DMSO-d6) δ 8.20 (d, J = 5.64 Hz, 1H), 6.75-6.70 (m, 1H), 6.52 (d, J = 5.64 Hz, 1H), 4.87-4.79 (m, 1H), 4.62-4.55 (m, 2H), 4.37-4.30 (m, 1H), 4.24-4.10 (m, 6H), 3.80-3.61 (m, 2H), 3.13-3.08 (m, 1H), 2.86-2.77 (m, 2H), 2.40-2.25 (m, 5H). Theoretical calculation value of ESI-MS: C 21 H 24 F3N6O [M+H]+ = 433.2, measured value: 433.2.

[1065] Example 2 Synthesis pathway:

[1066] [ka]

[1067] Step 1 2-1 (500 mg, 2.43 mmol) and potassium carbonate (672 mg, 4.86 mmol) were added to DMF (5 mL), and then methyl iodide (1.2 g, 7.28 mmol) was added. The mixture was stirred at room temperature for 16 hours. Water (15 mL) was added to the reaction mixture, extracted with ethyl acetate (5 mL x 3), the organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 2-2. Theoretical calculation value by ESI-MS: C8H8Cl2NO2[M+H] + = 220.0, measured value: 219.8.

[1068] Step 2 2-2 (1.0 g, 4.54 mmol), anhydrous potassium carbonate (3.7 g, 27.24 mmol), methylboronic acid (410 mg, 6.81 mmol), tris(2-methylphenyl)phosphine (140 mg, 0.45 mmol), and bis(triphenylphosphine)palladium(II) dichloride (640 mg, 0.91 mmol) were added to DMF (5 mL). The reaction system was heated to 80°C under the protection of nitrogen gas and stirred for 18 hours. The reaction mixture was cooled to room temperature, filtered, diluted with water (15 mL), extracted with ethyl acetate (5 mL x 3), the organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 9 / 1, v / v) to obtain 2-3. Theoretical calculation value of ESI-MS: C9H 11 ClNO2[M+H] + =200.0, Measured value: 200.0.

[1069] Step 3 2-3 (100 mg, 0.50 mmol), 2-4 (134.20 mg, 1.00 mmol), cesium fluoride (228 mg, 1.50 mmol), bis(triphenylphosphine)palladium(II) dichloride (35 mg, 0.05 mmol), and 1,4-dioxane (1.5 mL) were added to 5 mL microcentrifuge tubes. The reaction system was heated to 85 °C under the protection of nitrogen gas and stirred for 18 hours. The reaction mixture was cooled to room temperature, filtered, diluted with water (15 mL), extracted with ethyl acetate (5 mL x 3), washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 4 / 1, v / v) to obtain 2-5. Theoretical calculation value of ESI-MS: C 11 H 14 NO2 [M+H] + = 192.1, Measured value: 192.0.

[1070] Step 4 Compound 2-5 (140 mg, 0.73 mmol), intermediate D (220 mg, 0.95 mmol), N,N-diisopropylethylamine (284 mg, 2.20 mmol), and n-butanol (2 mL) were added to a 5 mL microcentrifuge tube, and the mixture was heated to 130 °C and stirred for 18 hours. The reaction mixture was cooled to room temperature, filtered, and the filtrate was concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by preparative HPLC (chromatography: Bonnasil-BR C18 21.2 × 250 mm, 10 μm, mobile phase: acetonitrile-0.1% formic acid aqueous solution, gradient: 7-37%, retention time: 9.5 min) to obtain compound 2. 1H NMR (400 MHz, DMSO-d6) δ 8.22 (d, J = 5.64 Hz, 1H), 7.03 (s, 1H), 6.70 (d, J = 2.27 Hz, 1H), 6.55-6.50 (m, 1H), 4.11 (t, J = 8.20 Hz, 2H), 3.85-3.76 (m, 4H), 3.62-3.55 (m, 2H), 3.21-3.10 (m, 1H), 3.00 (t, J = 6.50 Hz, 2H), 2.58 (s, 3H), 2.43 (s, 3H). Theoretical calculation value of ESI-MS: C 20 H 22 F3N4O [M+H] + = 391.2, measured value: 391.1.

[1071] Example 3 Synthesis pathway:

[1072] [ka]

[1073] Step 1 A-4 (500 mg, 1.73 mmol) was dissolved in tetrahydrofuran (5 mL), and the reaction mixture was cooled to -78°C under the protection of nitrogen gas. A solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (1 mol / L, 2.08 mL, 2.08 mmol) was added, and the mixture was stirred for 2 hours. Then, methyl iodide (295 mg, 2.08 mmol) was added dropwise, followed by stirring at -78°C for 1 hour, and the mixture was slowly raised to room temperature. A saturated ammonium chloride solution (10 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (10 mL x 3). The organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 13 / 7, v / v) to obtain 3-1. 1H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 5.66 Hz, 1H), 6.72 (d, J = 2.20 Hz, 1H), 6.53 (dd, J = 5.66, 2.20 Hz, 1H), 4.15-3.95 (m, 4H), 3.78-3.72 (m, 2H), 2.95-2.83 (m, 1H), 2.81-2.75 (m, 1H), 1.20-1.13 (m, 3H), 1.09 (d, J = 6.92 Hz, 3H). ESI-MS theoretical calculation value: C 14 H 18 F3N2O2[M+H] + = 303.1, measured value: 303.2.

[1074] Step 2 3-1 (200 mg, 0.66 mmol) was dissolved in tetrahydrofuran (5 mL) and water (1 mL), lithium hydroxide (42 mg, 0.99 mmol) was added, and the mixture was stirred at 40°C for 12 hours. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, water was added, and freeze-dried to obtain a crude product containing 3-2, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 12 H 14 F3N2O2[M+H] + =275.1, measured value: 275.2.

[1075] Step 3 The crude product containing 3-2 (180 mg, 0.66 mmol) and intermediate B (200 mg, 1.35 mmol) were dissolved in DMF (5 mL), DIEA (255 mg, 1.97 mmol) and HATU (300 mg, 0.97 mmol) were added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain the crude product containing the target compound, which was purified by preparative HPLC (chromatography: XBndge prep 19 × 250 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 34-64%, retention time: 9 min) to obtain compound 3. 1H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 5.68 Hz, 1H), 7.01 (s, 1H), 6.70 (s, 1H), 6.52 (d, J = 5.68 Hz, 1H), 5.10-4.95 (m, 1H), 4.90-4.78 (m, 1H), 4.64-4.50 (m, 2H), 4.15-4.08 (m, 1H), 4.05-3.98 (m, 1H), 3.83-3.76 (m, 1H), 3.72-3.60 (m, 1H), 3.12-2.98 (m, 2H), 2.43 (s, 3H), 2.23 (s, 3H), 1.15-1.09 (m, 3H). ESI-MS theoretical calculation value: C 21 H 24 F3N4O[M+H] + = 405.2, Measured value: 405.2.

[1076] Example 4 Synthesis pathway:

[1077] [ka]

[1078] Step 1 5 mL of tetrahydrofuran was added to the reaction mixture, and the mixture was cooled to -78°C under the protection of nitrogen gas. A hexane solution of lithium diisopropylamide (2 mol / L, 4.22 mL, 8.44 mmol) was added, and then 1.0 g of 4-1 (7.03 mmol) of tetrahydrofuran (5 mL) solution was added dropwise, and the mixture was stirred at -78°C for 2 hours. 5 mL of tetrahydrofuran solution of compound 4-2 (1.7 g, 8.44 mmol) was added dropwise to the reaction mixture. The mixture was then stirred at -78°C for 1 hour. 50 mL of water was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20 mL x 3). The organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 7 / 3, v / v) to obtain 4-3. 1H NMR (400 MHz, DMSO-d6) δ 7.17-7.03 (m, 5H), 5.55 (s, 1H), 4.80 (s, 2H), 3.71-3.57 (m, 2H), 3.55-3.39 (m, 2H), 1.13 (s, 9H), 0.77-0.69 (m, 2H), 0.63-0.56 (m, 2H). ESI-MS theoretical calculation value: C 19 H 26 NO5 [M+H] + = 348.2, measured value: 348.2.

[1079] Step 2 4-3 (13.0 g, 37.4 mmol) was dissolved in toluene (10 mL), Burgess reagent (10.7 g, 44.9 mmol) was added, and the mixture was heated to 90°C and stirred for 1 hour. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 7 / 3, v / v) to obtain 4-4. Theoretical calculation value of ESI-MS: C 19 H 23 NNaO4[M+Na] + =352.2, actual value: 352.0.

[1080] Step 3 4-4 (1.6 g, 4.86 mmol) was dissolved in methanol (10 mL), wet palladium carbon (10%, 100 mg) was added, and the reaction system was purged three times with hydrogen gas. The mixture was then stirred at room temperature for 18 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain 4-5. Theoretical calculation value by ESI-MS: C 11 H 20 NO2 [M+H] + = 198.1, Measured value: 198.1.

[1081] Step 4 4-5 (700 mg, 3.55 mmol), A-3 (644 mg, 3.55 mmol), cesium fluoride (538.98 mg, 3.55 mmol), triethylamine (1.08 g, 10.64 mmol), and DMSO (10 mL) were added to a 20 mL microtube and heated to 100 °C, stirring for 18 hours. After cooling the reaction mixture, water (30 mL) was added, and the mixture was extracted with ethyl acetate (10 mL x 3). The organic phases were combined, washed with saturated brine (30 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 1, v / v) to obtain 4-6. Theoretical calculation value of ESI-MS: C 17 H 22 F3N2O2[M+H] + =343.2, measured value: 343.0.

[1082] Step 5 5-5 (150 mg, 0.44 mmol) was dissolved in hydrochloric acid (3 mol / L, 2 mL), and the mixture was heated to 40°C and stirred for 3 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to obtain 5-6. Theoretical value calculated by ESI-MS: C 13 H 14 F3N2O2[M+H] + = 287.1, Measured value: 287.0.

[1083] Step 6 Compounds 5-6 (125 mg, 0.44 mmol), HATU (249 mg, 0.66 mmol), DIEA (564 mg, 4.37 mmol), and intermediate B (84 mg, 0.57 mmol) were added to tetrahydrofuran (3 mL) and stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by preparative HPLC (chromatography: XBndge C18 19 × 250 mm, 10 μm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 34-44%, retention time: 9.5 min) to obtain compound 4. 1H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 5.66 Hz, 1H), 7.01 (s, 1H), 6.73 (d, J = 2.26 Hz, 1H), 6.53 (dd, J = 5.66, 2.26 Hz, 1H), 4.98-4.75 (m, 2H), 4.73-4.48 (m, 2H), 4.08-4.01 (m, 2H), 3.69-3.61 (m, 2H), 3.50-3.40 (m, 1H), 2.43 (s, 3H), 2.24 (s, 3H), 1.02-0.95 (m, 2H), 0.89-0.82 (m, 2H). Theoretical calculation value of ESI-MS: C 22 H 24 F3N4O[M+H] + = 417.2, measured value: 417.1.

[1084] Example 5 Synthesis pathway:

[1085] [ka]

[1086] Step 1 Intermediate B (100 mg, 0.70 mmol), HATU (267 mg, 0.70 mmol), and DIEA (91 mg, 2.02 mmol) were dissolved in tetrahydrofuran (2 mL) and stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by preparative HPLC (chromatography: XBndge C18 19 × 250 mm, 10 μm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 26-56%, retention time: 7.5 min) to obtain compound 5. 1H NMR (400 MHz, DMSO-d6) δ 7.48 (dd, J = 4.92, 2.96 Hz, 1H), 7.37-7.31 (m, 1H), 7.10-7.05 (m, 1H), 7.00 (d, J = 4.90 Hz, 1H), 4.90-4.82 (m, 2H), 4.63-4.55 (m, 2H), 3.78 (s, 2H), 2.42 (s, 3H), 2.23 (s, 3H). ESI-MS theoretical calculation value: C 15 H 17 N2OS [M+H] + = 273.1, measured value: 273.2.

[1087] Example 6 Synthesis pathway:

[1088] [ka]

[1089] Step 1 Intermediate E (200 mg, 1.00 mmol), triethylamine (505 mg, 4.99 mmol), and intermediate A (371 mg, 1.00 mmol) were dissolved in DMF (2 mL), HATU (456 mg, 1.20 mmol) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by preparative HPLC (chromatography: XBndge C18 19 × 250 mm, 10 μm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 30-52%, retention time: 9.5 min) to obtain compound 6. 1HNMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 5.72 Hz, 1H), 6.71 (d, J = 2.23 Hz, 1H), 6.53 (dd, J = 5.82, 2.3 Hz, 1H), 4.83-4.68 (m, 2H), 4.59-4.44 (m, 2H), 4.21-4.14 (m, 2H), 3.73-3.66 (m, 2H), 3.18-3.06 (m, 1H), 2.85-2.78 (m, 2H), 2.68 (s, 3H). ESI-MS theoretical calculation: 17 H 18 F3N4OS [M+H] + = 383.1, measured value: 383.0.

[1090] Example 7 Synthesis pathway:

[1091] [ka]

[1092] Step 1 Dimethylamine hydrochloride (230 mg, 2.87 mmol) and C-3 (600 mg, 2.40 mmol) were dissolved in DMF (10 mL), and DBU (1.1 g, 7.20 mmol) and PyBOP (1.5 g, 2.90 mmol) were added sequentially. The mixture was heated to 80°C and stirred for 18 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 9, v / v) to obtain 7-1. 1 H NMR (400 MHz, DMSO-d6) δ 4.87-4.72 (m, 2H), 4.34-4.26 (m, 2H), 3.13-3.10 (m, 6H), 2.35 (s, 3H), 1.45 (s, 9H). ESI-MS theoretical calculation value: C 14 H 23 N4O2[M+H] + = 279.2, Measured value: 279.2.

[1093] Step 2 7-1 (570 mg, 1.80 mmol) was dissolved in dichloromethane (10 mL) and trifluoroacetate (10 mL), and the mixture was stirred at room temperature for 2 hours. After concentrating the reaction mixture under reduced pressure, trifluoroacetate 7-2 was obtained. 1 H NMR (400 MHz, DMSO-d6) δ 4.86 (s, 2H), 4.53 (s, 2H), 3.30 (s, 6H), 2.53 (s, 3H). ESI-MS theoretical calculation value: C9H 15 N4[M+H] + = 179.1, measured value: 179.2.

[1094] Step 3 7-2 trifluoroacetate (320 mg, 1.80 mmol) and intermediate A (600 mg, 1.61 mmol) were dissolved in DMF (10 mL), DIEA (630 mg, 4.80 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Then HATU (920 mg, 2.40 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by preparative HPLC (chromatography: Pntulips BP-C18, 5 μm, 21.2 × 150 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 40-70%, retention time: 9 min) to obtain compound 7. 1 H NMR (400 MHz, DMSO-d6) δ 8.20 (d, J = 5.66 Hz, 1H), 6.77-6.66 (m, 1H), 6.52 (dd, J = 5.38, 1.98 Hz, 1H), 5.10-5.03 (m, 1H), 4.87-4.81 (m, 1H), 4.61-4.55 (m, 1H), 4.37-4.30 (m, 1H), 4.20-4.12 (m, 2H), 3.71-3.67 (m, 2H), 3.12 (s, 6H), 2.83 (dd, J = 15.74, 7.66 Hz, 2H), 2.35 (s, 3H). Theoretical calculation value of ESI-MS: C 20 H 24 F3N6O [M+H] + = 421.2, measured value: 421.2.

[1095] Example 8 Synthesis pathway:

[1096] [ka]

[1097] Step 1 Intermediate A (100 mg, 0.38 mmol), HATU (219 mg, 0.58 mmol), DIEA (248 mg, 1.92 mmol), and trifluoroacetate of intermediate F (114 mg, 0.77 mmol) were added to tetrahydrofuran (3 mL) and stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by preparative HPLC (chromatography: XBndge C18 19 × 250 mm, 10 μm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 25-37%, retention time: 8 min) to obtain compound 8. 1 H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 5.67 Hz, 1H), 6.72 (d, J = 2.25 Hz, 1H), 6.53 (dd, J = 5.68, 2.24 Hz, 1H), 4.88-4.78 (m, 2H), 4.65-4.55 (m, 2H), 4.18 (t, J = 8.26 Hz, 2H), 3.74-3.66 (m, 2H), 3.20-3.06 (m, 1H), 2.89-2.83 (m, 2H), 2.58 (s, 3H), 2.42-2.37 (m, 3H). ESI-MS theoretical calculation value: C 19 H 21 F3N5O [M+H] + = 392.2, measured value: 392.1.

[1098] Example 9 Synthesis pathway:

[1099] [ka]

[1100] Step 1 Intermediate B trifluoroacetate (100 mg, 0.67 mmol), HATU (308 mg, 0.81 mmol), triethylamine (341 mg, 3.37 mmol), and 9-1 (96 mg, 0.67 mmol) were dissolved in DMF (3 mL) and stirred at room temperature for 3 hours. The reaction mixture was poured into water (10 mL), extracted with ethyl acetate (10 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product of the target compound. This product was purified by preparative HPLC (chromatography: XBndge C18 19 × 250 mm, 10 μm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 24-50%, retention time: 8.5 min) to obtain compound 9. 1 H NMR (400 MHz, DMSO-d6) δ 7.40 (dd, J = 4.92, 1.6 Hz, 1H), 7.03 - 6.97 (m, 3H), 4.93-4.82 (m, 2H), 4.65-4.57 (m, 2H), 4.03 (s, 2H), 2.43 (s, 3H), 2.24 (s, 3H). ESI-MS theoretical calculation value: C 15 H 17 N2OS [M+H] + = 273.1, measured value: 273.0.

[1101] Example 10 Synthesis pathway:

[1102] [ka]

[1103] Step 1 10-1 (300 mg, 2.17 mmol) and the trifluoroacetate of intermediate B (644 mg, 4.34 mmol) were dissolved in DMF (5 mL), DIEA (842 mg, 6.52 mmol) and HATU (991 mg, 2.61 mmol) were added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the compound, which was purified by preparative HPLC (chromatography: XBndge prep 21.2 × 150 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 10-40%, retention time: 9 min) to obtain compound 10. 1 H NMR (400 MHz, DMSO-d6) δ 8.80-8.73 (m, 2H), 7.44-7.38 (m, 1H), 7.04-6.98 (m, 1H), 4.98-4.86 (m, 2H), 4.66-4.56 (m, 2H), 4.10 (s, 2H), 2.46-2.40 (m, 3H), 2.27-2.19 (m, 3H). ESI-MS theoretical calculation: C 15 H 17 N4O [M+H] + = 269.1, measured value: 269.1.

[1104] Example 11 Synthesis pathway:

[1105] [ka]

[1106] Step 1 Compound 11 (250 mg, 1.81 mmol) and the trifluoroacetate of intermediate B (536 mg, 3.62 mmol) were dissolved in DMF (5 mL), DIEA (702 mg, 5.43 mmol) and HATU (826 mg, 2.17 mmol) were added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by preparative HPLC (chromatography: XBndge prep 21.2 × 150 mm, mobile phase: aqueous solution of acetonitrile-10 mmol / L ammonium bicarbonate, gradient: 10-40%, retention time: 9 min) to obtain compound 11.1 H NMR (400 MHz, DMSO-d6) δ 9.08 (s, 1H), 8.73-8.69 (m, 2H), 7.06-7.01 (m, 1H), 5.00-4.92 (m, 2H), 4.66-4.57 (m, 2H), 3.89 (s, 2H), 2.44 (s, 3H), 2.29-2.23 (m, 3H). ESI-MS theoretical calculation: C 15 H 17 N4O [M+H] + = 269.1, measured value: 269.1.

[1107] Example 12 Synthesis pathway:

[1108] [ka]

[1109] Step 1 Intermediate G (50 mg, 0.26 mmol), HATU (149.9 mg, 0.39 mmol), DIEA (0.13 mL, 0.79 mmol), and intermediate A (136.8 mg, 0.53 mmol) were added to tetrahydrofuran (2 mL) and stirred at room temperature for 3 hours. The reaction mixture was filtered and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by preparative HPLC (chromatography: Waters-Xbridge-C18-10 μm-19 × 250 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 20-50%, retention time: 9 min) to obtain compound 12. 1H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 5.66 Hz, 1H), 6.74-6.70 (m, 1H), 6.56-6.51 (m, 1H), 4.88-4.84 (m, 1H), 4.81-4.77 (m, 1H), 4.66-4.61 (m, 1H), 4.58-4.55 (m, 1H), 4.19-4.14 (m, 2H), 4.13-4.08 (m, 4H), 3.73-3.65 (m, 2H), 3.17-3.06 (m, 1H), 2.89-2.80 (m, 2H), 2.40 (s, 3H), 2.38-2.29 (m, 2H). ESI-MS theoretical calculation: C 21 H 24 F3N6O [M+H] + = 433.2, measured value: 433.2.

[1110] Example 13 Synthesis pathway:

[1111] [ka]

[1112] Step 1 Intermediate B trifluoroacetate (650 mg, 4.39 mmol), 13-1 (300 mg, 2.19 mmol), HATU (1.24 g, 3.26 mmol), and DIEA (848 mg, 6.19 mmol) were dissolved in DMF (3 mL) and stirred at room temperature for 3 hours. The reaction mixture was diluted with water (10 mL), extracted with ethyl acetate (10 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target product. This crude product was purified by preparative HPLC (chromatography: Pntulips BP-C18, 5 μm, 21.2 × 150 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 53-83%, retention time: 9 min) to obtain compound 13. 1H NMR (400 MHz, DMSO-d6) δ 8.64-8.37 (m, 2H), 7.31 (dd, J = 5.60, 3.66 Hz, 2H), 7.00 (d, J = 5.08 Hz, 1H), 4.93-4.81 (m, 2H), 4.63-4.54 (m, 2H), 3.84 (s, 2H), 2.42 (s, 3H), 2.25-2.21 (m, 3H). Theoretical calculation value of ESI-MS: C 16 H 18 N3O [M+H] + = 268.1, Measured value: 268.1.

[1113] Example 14 Synthesis pathway:

[1114] [ka]

[1115] Step 1 14-1 (200 mg, 2.82 mmol) and C-3 (600 mg, 2.39 mmol) were dissolved in DMF (10 mL), DBU (730 mg, 4.80 mmol) and PyBOP (1.5 g, 2.90 mmol) were added, and the mixture was heated to 80°C and stirred for 18 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 9, v / v) to obtain 14-2. 1 H NMR (400 MHz, DMSO-d6) δ 7.50-7.47 (m, 1H), 4.62-4.40 (m, 4H), 3.43-3.36 (m 2H), 2.51 (s, 3H), 1.53 (s, 9H), 1.26-1.15 (m, 1H), 0.71-0.53 (m, 2H), 0.52-0.34 (m, 2H). Theoretical calculation value of ESI-MS: C 16 H 25 N4O2[M+H] + = 305.2, measured value: 305.2.

[1116] Step 2 14-2 (520 mg, 1.71 mmol) was dissolved in dichloromethane (10 mL) and trifluoroacetate (10 mL), and the mixture was stirred at room temperature for 2 hours. After concentrating the reaction mixture under reduced pressure, trifluoroacetate 14-3 was obtained. 1 H NMR (400 MHz, DMSO-d6) δ 4.57-4.50 (m, 2H), 4.43-4.34 (m, 2H), 3.44-3.32 (m, 2H), 2.51 (s, 3H), 1.06-0.99 (m, 1H), 0.55-0.38 (m, 2H), 0.30-0.18 (m, 2H). ESI-MS theoretical calculation value: C 11 H 17 N4[M+H] + = 205.1, measured value: 205.2.

[1117] Step 3 330 mg, 1.59 mmol of trifluoroacetate 14-3 and intermediate A (500 mg, 1.92 mmol) were dissolved in DMF (10 mL), 750 mg, 5.81 mmol of DIEA was added, and the mixture was stirred at room temperature for 30 minutes. Then, 880 mg, 2.32 mmol of HATU was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain the crude product of the target compound, which was purified by preparative HPLC (chromatography: Pntulips BP-C18, 5 μm, 21.2 × 150 mm, mobile phase: aqueous solution of acetonitrile-10 mmol / L ammonium bicarbonate, gradient: 35-65%, retention time: 9 min) to obtain compound 14. 1H NMR (400 MHz, DMSO-d6) δ 8.20 (dd, J = 5.70, 1.70 Hz, 1H), 7.36-7.29 (m, 1H), 6.71 (d, J = 2.24 Hz, 1H), 6.52 (dd, J = 5.74, 2.22 Hz, 1H), 4.60-4.55 (m, 2H), 4.37 (d, J = 10.94 Hz, 2H), 4.17 (t, J = 8.28 Hz, 2H), 3.71-3.67 (m, 2H), 3.28-3.18 (m, 2H), 3.14-3.08 (m, 1H), 2.84-2.79 (m, 2H), 2.35 (s, 3H), 1.14-0.96 (m, 1H), 0.45-0.40 (m, 2H), 0.24-0.20 (m, 2H). ESI-MS theoretical calculation value: C 22 H 26 F3N6O [M+H] + = 447.2, measured value: 447.2.

[1118] Example 15 Synthesis pathway:

[1119] [ka]

[1120] Step 1 Intermediate B (500 mg, 1.69 mmol) and potassium carbonate (1.2 g, 8.43 mmol) were added to dichloromethane (10 mL). Chloroacetyl chloride (228 mg, 2.02 mmol) was added at 0°C, and the mixture was slowly heated to room temperature and stirred for 3 hours. Water (10 mL) was added to the reaction mixture to quench it, and the mixture was extracted with dichloromethane (10 mL x 3). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing target compound 15-1, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C 11 H 14 ClN2O[M+H] + =225.1, measured value: 225.0.

[1121] Step 2 The trifluoroacetate of intermediate H (216 mg, 0.89 mmol), DIEA (575 mg, 4.45 mmol), and 15-1 (200 mg, 0.89 mmol) were added to acetonitrile (4 mL) and stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the compound, which was purified by preparative HPLC (chromatography: XBndge C18 19 × 250 mm, 10 μm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 25-50%, retention time: 10.5 min) to obtain compound 15. 1 HNMR (400 MHz, DMSO-d6) δ 8.22 (d, J = 5.60 Hz, 1H), 6.98 (s, 1H), 6.69 (d, J = 2.24 Hz, 1H), 6.52 (dd, J = 5.62, 2.28 Hz, 1H), 4.80-4.73 (m, 2H), 4.56-4.52 (m, 2H), 4.10 (s, 4H), 3.50 (s, 4H), 3.35-3.34 (m, 2H), 2.44 (s, 3H), 2.24 (s, 3H). ESI-MS theoretical calculation value: C 22 H 25 F3N5O [M+H] + = 432.2, measured value: 432.2.

[1122] Example 16 Synthesis pathway:

[1123] [ka]

[1124] Step 1 16-1 (400 mg, 2.65 mmol) was dissolved in tetrahydrofuran (5 mL) and water (1 mL), lithium hydroxide (167 mg, 3.98 mmol) was added, and the mixture was stirred at 40°C for 12 hours. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, water was added, and freeze-dried to obtain a crude product containing 16-2, which was used directly in the next step of the reaction. Theoretical calculation value by ESI-MS: C7H8NO2[M+H]+ = 138.1, measured value: 138.0.

[1125] Step 2 Compound 16-2 (360 mg, 2.63 mmol) and the trifluoroacetate of intermediate B (778 mg, 5.25 mmol) were dissolved in DMF (5 mL), DIEA (1.02 g, 7.88 mmol) and HATU (1.20 g, 3.15 mmol) were added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain the crude product of the target compound, which was purified by preparative HPLC (chromatography: XBndge prep 21.2 × 150 mm, mobile phase: aqueous solution of acetonitrile-10 mmol / L ammonium bicarbonate, gradient: 20-50%, retention time: 9 min) to obtain compound 16. 1 H NMR (400 MHz, DMSO-d6) δ 8.53-8.47 (m, 1H), 7.80-7.72 (m, 1H), 7.40-7.33 (m, 1H), 7.31-7.25 (m, 1H), 7.04-6.99 (m, 1H), 5.00-4.89 (m, 2H), 4.64-4.56 (m, 2H), 3.96 (s, 2H), 2.43 (s, 3H), 2.24 (s, 3H). ESI-MS theoretical calculation value: C 16 H 18 N3O [M+H] + = 268.1, Measured value: 268.1.

[1126] Example 17 Synthesis pathway:

[1127] [ka]

[1128] Step 1 Intermediate B trifluoroacetate (100 mg, 0.68 mmol), 17-1 (100 mg, 0.73 mmol), HATU (267 mg, 0.70 mmol), and DIEA (349 mg, 2.03 mmol) were dissolved in tetrahydrofuran (2 mL) and stirred at room temperature for 3 hours. The reaction mixture was filtered and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by preparative HPLC (chromatography: Waters-Xbridge-C18-10 μm-19 × 250 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 6-36%, retention time: 12 min) to obtain compound 17. 1 H NMR (400 MHz, DMSO-d6) δ 8.50-8.45 (m, 2H), 7.72-7.66 (m, 1H), 7.45-7.38 (m, 1H), 7.02 (d, J = 5.79 Hz, 1H), 4.97-4.90 (m, 2H), 4.64-4.56 (m, 2H), 3.84 (s, 2H), 2.44 (s, 3H), 2.26-2.24 (m, 3H). ESI-MS theoretical calculation value: C 16 H 18 N3O [M+H] + = 268.1, Measured value: 268.1.

[1129] Example 18 Synthesis pathway:

[1130] [ka]

[1131] Step 1 Intermediate B trifluoroacetate (200 mg, 1.35 mmol), 18-1 (150 mg, 1.05 mmol), HATU (513 mg, 1.35 mmol), and DIEA (349 mg, 2.70 mmol) were dissolved in tetrahydrofuran (2 mL) and stirred at room temperature for 3 hours. The reaction mixture was filtered and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by preparative HPLC (chromatography: Waters-Xbridge-C18-10 μm-19 × 250 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 5-35%, retention time: 12 min) to obtain compound 18. 1 H NMR (400 MHz, DMSO-d6) δ 9.05 (s, 1H), 7.55 (s, 1H), 7.03-7.01 (m, 1H), 4.99-4.90 (m, 2H), 4.64-4.56 (m, 2H), 3.97 (s, 2H), 2.43 (s, 3H), 2.23 (s, 3H). ESI-MS theoretical calculation value: C 14 H 16 N3OS [M+H] + = 274.1, measured value: 274.2.

[1132] Example 19 Synthesis pathway:

[1133] [ka]

[1134] Step 1 Intermediate B trifluoroacetate (150 mg, 1.02 mmol), 19-1 (350 mg, 2.57 mmol), HATU (675 mg, 1.78 mmol), and DIEA (922 mg, 3.33 mmol) were dissolved in DMF (5 mL) and stirred at room temperature for 3 hours. The reaction mixture was poured into water (10 mL), extracted with ethyl acetate (10 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by preparative HPLC (chromatography: Pntulips BP-C18, 5 μm, 21.2 × 150 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 58-88%, retention time: 9 min) to obtain compound 19. 1 H NMR (400 MHz, DMSO-d6) δ 7.59-7.57 (m, 1H), 7.13-7.10 (m, 1H), 7.03 (d, J = 7.45 Hz, 1H), 6.89 (s, 1H), 5.06 (s, 2H), 4.90-4.85 (m, 2H), 4.65-4.58 (m, 2H), 2.44 (s, 3H), 2.26-2.23 (m, 3H). ESI-MS theoretical calculation value: C 14 H 17 N4O [M+H] + = 257.1, measured value: 257.1.

[1135] Example 20 Synthesis pathway:

[1136] [ka]

[1137] Step 1 20-1 (1.0 g, 8.4 mmol) was dissolved in tetrahydrofuran (10 mL), cooled to 0°C, sodium hydride (60%, 670 mg, 16.8 mmol) was added and stirred for 30 minutes, then ethyl bromo (1.54 g, 9.2 mmol) was added dropwise and stirred at room temperature for 18 hours. The reaction mixture was slowly poured into water (10 mL), ethyl acetate (20 mL x 3) was added for extraction, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 4 / 1, v / v) to obtain 20-2. Theoretical calculation value of ESI-MS: C 12 H 16 NO2 [M+H] + = 206.1, Measured value: 206.1.

[1138] Step 2 20-2 (1.1 g, 5.36 mmol) was dissolved in methanol (10 mL) and water (3 mL), lithium hydroxide monohydrate (670 mg, 16.1 mmol) was added, and the mixture was stirred at room temperature for 3 hours. The pH of the reaction solution was adjusted to 3 with dilute hydrochloric acid (1 mol / L), a solid precipitated, and the mixture was filtered to obtain 20-3. Theoretical calculation value by ESI-MS: C 10 H 12 NO2 [M+H] + = 178.1, Measured value: 178.0.

[1139] Step 3 Intermediate B (251 mg, 0.85 mmol) and 20-3 (150 mg, 0.85 mmol) were dissolved in DMF (3 mL), TEA (429 mg, 4.2 mmol) and HATU (386 mg, 1.02 mmol) were added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into water (10 mL), ethyl acetate (10 mL x 3) was added for extraction, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by preparative HPLC (chromatography: XBridge C18 19 × 250 mm, 10 μm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 20-55%, retention time: 8.5 min) to obtain compound 20.1 H NMR (400 MHz, DMSO-d6) δ 7.05-6.99 (m, 2H), 6.95 (t, J = 7.62 Hz, 1H), 6.56 (t, J = 7.42 Hz, 1H), 6.52 (dd, J = 7.80, 2.7 Hz, 1H), 4.93-4.85 (m, 2H), 4.63-4.56 (m, 2H), 4.10-4.05 (m, 2H), 3.55-3.48 (m, 2H), 2.98-2.90 (m, 2H), 2.43 (s, 3H), 2.24 (s, 3H). Theoretical calculation value of ESI-MS: C 19 H 22 N3O [M+H] + = 308.2, measured value: 308.1.

[1140] Example 21 Synthesis pathway:

[1141] [ka]

[1142] Step 1 Intermediate B (208 mg, 0.70 mmol) and 21-1 (100 mg, 0.70 mmol) were dissolved in DMF (3 mL), TEA (353 mg, 3.5 mmol) and HATU (319 mg, 0.84 mmol) were added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into water (10 mL), ethyl acetate (10 mL x 3) was added for extraction, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by preparative HPLC (chromatography: XBridge C18 19 × 250 mm, 10 μm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 25-45%, retention time: 7.5 min) to obtain compound 21. 1H NMR (400 MHz, DMSO-d6) δ 7.76 (d, J = 3.30 Hz, 1H), 7.67 (d, J = 3.30 Hz, 1H), 7.02 (d, J = 5.32 Hz, 1H), 4.99-4.90 (m, 2H), 4.67-4.58 (m, 2H), 4.29 (s, 2H), 2.43 (s, 3H), 2.24 (s, 3H). ESI-MS theoretical calculation value: C 14 H 16 N3OS [M+H] + = 274.1, measured value: 274.1.

[1143] Example 22 Synthesis pathway:

[1144] [ka]

[1145] Step 1 Intermediate B (158 mg, 0.53 mmol) and 22-1 (100 mg, 0.53 mmol) were dissolved in DMF (4 mL), TEA (270 mg, 2.67 mmol) and HATU (244 mg, 0.64 mmol) were added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into water (10 mL), ethyl acetate (10 mL x 3) was added for extraction, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by preparative HPLC (chromatography: XBridge C18 19 × 250 mm, 10 μm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 28-42%, retention time: 8.3 min) to obtain compound 22. 1H NMR (400 MHz, DMSO-d6) δ 8.87 (dd, J = 4.20, 1.72 Hz, 1H), 8.34 (dd, J = 8.32, 2.02 Hz, 1H), 7.98 (d, J = 8.60 Hz, 1H), 7.87 (d, J = 2.22 Hz, 1H), 7.71-7.69 (m, 1H), 7.52 (dd, J = 8.32, 4.20 Hz, 1H), 7.01 (d, J = 6.60 Hz, 1H), 4.99-4.90 (m, 2H), 4.68-4.60 (m, 2H), 4.01 (s, 2H), 2.43 (s, 3H), 2.24 (s, 3H). ESI-MS theoretical calculation value: C 20 H 20 N3O [M+H] + = 318.2, measured value: 318.1.

[1146] Example 23 Synthesis pathway:

[1147] [ka]

[1148] Step 1 Intermediate B (197 mg, 0.67 mmol) and 23-1 (100 mg, 0.67 mmol) were dissolved in DMF (4 mL), TEA (337 mg, 3.33 mmol) and HATU (309 mg, 0.80 mmol) were added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into water (10 mL), ethyl acetate (10 mL x 3) was added for extraction, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by preparative HPLC (chromatography: XBridge C18 19 × 250 mm, 10 μm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 30-55%, retention time: 9.5 min) to obtain compound 23. 1H NMR (400 MHz, DMSO-d6) δ 7.20-7.10 (m, 4H), 7.00 (d, J = 5.24 Hz, 1H), 4.88-4.79 (m, 2H), 4.63-4.55 (m, 2H), 3.72 (s, 2H), 2.42 (s, 3H), 2.28 (s, 3H), 2.23 (s, 3H). ESI-MS theoretical calculation value: C 18 H 21 N2O [M+H] + = 281.2, measured value: 281.1.

[1149] Example 24 Synthesis pathway:

[1150] [ka]

[1151] Step 1 Intermediate I trifluoroacetate (100 mg, 0.67 mmol) and intermediate A (262 mg, 1.01 mmol) were dissolved in tetrahydrofuran (4 mL), DIEA (260 mg, 2.01 mmol) and HATU (382 mg, 1.01 mmol) were added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by preparative HPLC (chromatography: Waters-Xbridge C18 10 μm, 19 × 250 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 17-47%, retention time: 9 min) to obtain compound 24. 1H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 5.66 Hz, 1H), 6.72 (d, J = 2.24 Hz, 1H), 6.54 (dd, J = 5.66, 2.24 Hz, 1H), 4.95-4.90 (m, 2H), 4.76-4.69 (m, 2H), 4.22-4.15 (m, 2H), 3.75-3.68 (m, 2H), 3.17-3.10 (m, 1H), 2.90-2.82 (m, 2H), 2.57-2.52 (m, 6H). Theoretical calculation value of ESI-MS: C 19 H 21 F3N5O [M+H] + = 392.2, Measured value: 392.2.

[1152] Example 25 Synthesis pathway:

[1153] [ka]

[1154] Step 1 Intermediate A (500 mg, 1.35 mmol) and 25-1 (160 mg, 1.48 mmol) were dissolved in DMF (10 mL), DIEA (350 mg, 2.69 mmol) and HATU (770 mg, 2.02 mmol) were added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into water (10 mL), ethyl acetate (10 mL x 3) was added for extraction, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by preparative HPLC (chromatography: Pntulips BP-C18 21.2 × 250 mm, 5 μm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 18-28%, retention time: 9 min) to obtain compound 25. 1H NMR (400 MHz, DMSO-d6) δ 11.80 (br, 1H), 8.21 (d, J = 5.64 Hz, 1H), 7.99 (t, J = 5.68 Hz, 1H), 7.53 (s, 1H), 6.82-6.78 (m, 1H), 6.70 (d, J = 2.26 Hz, 1H), 6.51 (dd, J = 5.70, 2.26 Hz, 1H), 4.09 (t, J = 8.24 Hz, 2H), 3.68-3.63 (m, 2H), 3.30-3.24 (m, 2H), 3.05-2.97 (m, 1H), 2.52-2.46 (m, 4H). Theoretical calculation value of ESI-MS: C 16 H 19 F3N5O [M+H] + = 354.2, measured value: 354.1.

[1155] Example 26 Synthesis pathway:

[1156] [ka]

[1157] Step 1 Intermediate J (20 mg, 0.10 mmol) and intermediate A (64 mg, 0.17 mmol) were dissolved in DMF (10 mL), DIEA (66 mg, 0.51 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Then HATU (97 mg, 0.26 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by preparative HPLC (chromatography: Pntulips BP-C18, 5 μm, 21.2 × 150 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 35-52%, retention time: 9 min) to obtain compound 26. 1H NMR (400 MHz, DMSO-d6) δ 8.20 (d, J = 5.64 Hz, 1H), 6.89 (d, J = 6.30 Hz, 1H), 6.67 (s, 1H), 6.50 (d, J = 5.22 Hz, 1H), 4.15-4.06 (m, 2H), 3.68-3.52 (m, 6H), 3.12-3.07 (m, 1H), 3.06-2.95 (m, 2H), 2.92-2.85 (m, 1H), 2.83-2.77 (m, 3H), 2.34-2.27 (m, 3H), 2.22 (s, 3H). ESI-MS theoretical calculation value: C 22 H 26 F3N4O [M+H] + = 419.2, measured value: 419.2.

[1158] Example 27 Synthesis pathway:

[1159] [ka]

[1160] Step 1 A-3 (1.0 g, 5.51 mmol), hydrochloride of 27-1 (840 mg, 5.51 mmol), cesium fluoride (840 mg, 5.51 mmol), and TEA (2.23 g, 22.0 mmol) were added to DMSO (10 mL), and the mixture was heated to 80°C and stirred for 12 hours. After the reaction was complete, the mixture was diluted with water (80 mL), extracted with ethyl acetate (40 mL x 3), the organic phases were combined, washed with saturated brine (40 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was then purified by silica gel column chromatography (petroleum ether / ethyl acetate, 4 / 1, v / v) to obtain 27-2. 1HNMR (400 MHz, DMSO-d6) δ 8.25-8.22 (m, 1H), 6.79-6.75 (m, 1H), 6.58-6.54 (m, 1H), 4.25-4.18 (m, 2H), 4.15-4.08 (m, 2H), 3.75-3.67 (m, 1H), 3.65 (s, 3H). ESI-MS theoretical calculation value: C 11 H 12 F3N2O2[M+H] + = 261.0, Measured value: 261.0.

[1161] Step 2 27-2 (300 mg, 1.15 mmol), TEA (117 mg, 1.15 mmol), and 27-3 (210 mg, 1.72 mmol) were added to tetrahydrofuran (5 mL), cooled to 0°C, and then tert-butylmagnesium chloride solution in tetrahydrofuran (1 mol / L, 3.46 mL, 3.46 mmol) was added dropwise, and the mixture was stirred at room temperature for 12 hours. The reaction mixture was diluted with saturated sodium bicarbonate solution (30 mL), extracted with ethyl acetate (40 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1 / 1, v / v) to obtain 27-4. 1 H NMR (400 MHz, DMSO-d6) δ 8.27-8.24 (m, 1H), 6.79-6.76 (m, 1H), 6.60-6.56 (m, 1H), 4.64 (s, 2H), 4.20-4.13 (m, 2H), 4.10-4.02 (m, 2H), 3.97-3.93 (m, 1H). ESI-MS theoretical calculation value: C 11 H 11 ClF3N2O [M+H] + = 279.0, Measured value: 279.0.

[1162] Step 3 Intermediate B (76.2 mg, 0.36 mmol), potassium carbonate (100 mg, 0.72 mmol), TEA (72 mg, 0.72 mmol), tetrabutylammonium bromide (23 mg, 0.07 mmol), and 27-4 (100 mg, 0.36 mmol) were added to tetrahydrofuran (10 mL) and stirred at room temperature for 3 hours. The reaction mixture was diluted with water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by preparative HPLC (chromatography: XBndge C18 19 × 250 mm × 10 μm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 22-50%, retention time: 9.5 min) to obtain compound 27. 1 H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 5.62 Hz, 1H), 6.89 (s, 1H), 6.78 (d, J = 2.30 Hz, 1H), 6.58 (dd, J = 5.62, 2.30 Hz, 1H), 4.19-4.15 (m, 2H), 4.11-4.08 (m, 2H), 3.99-3.93 (m, 5H), 3.79 (s, 2H), 2.39 (s, 3H), 2.17 (s, 3H). ESI-MS theoretical calculation value: C 20 H 22 F3N4O [M+H] + = 391.2, Measured value: 391.2.

[1163] Example 28 Synthesis pathway:

[1164] [ka]

[1165] Step 1 28-1 (2.0 g, 15.0 mmol) was dissolved in tetrahydrofuran (20 mL), cooled to 0°C, then sodium hydride (60%, 670 mg, 16.8 mmol) was added, followed by dropwise addition of ethyl bromo (3.0 g, 18.0 mmol). The mixture was stirred at room temperature for 18 hours. The reaction mixture was slowly poured into saturated sodium bicarbonate solution, extracted with ethyl acetate (30 mL x 1), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3 / 2, v / v) to obtain 28-2. Theoretical calculation value of ESI-MS: C 13 H 18 NO2 [M+H] + = 220.1, Measured value: 220.1.

[1166] Step 2 28-2 (800 mg, 3.65 mmol) was dissolved in methanol (5 mL) and water (1 mL), lithium hydroxide monohydrate (153 mg, 3.65 mmol) was added, and the mixture was stirred at room temperature for 3 hours. After the reaction was complete, the pH of the reaction solution was adjusted to 5 with dilute hydrochloric acid (1 mol / L), concentrated under reduced pressure, and then freeze-dried to obtain a crude product containing 28-3, which was used directly in the next step of the reaction. 1 H NMR (400 MHz, DMSO-d6) δ 6.96-6.85 (m, 2H), 6.51-6.47 (m, 1H), 6.38-6.36 (m, 1H), 3.98 (s, 2H), 3.35-3.30 (m, 2H), 2.70-2.67 (m, 2H), 1.90-1.82 (m, 2H). ESI-MS theoretical calculation value: C 11 H 14 NO2 [M+H] + = 192.1, Measured value: 192.1.

[1167] Step 3 Intermediate B (279 mg, 1.88 mmol) and 28-3 (300 mg, 1.57 mmol) were dissolved in DMF (5 mL), DIEA (608 mg, 4.71 mmol) and HATU (894 mg, 2.35 mmol) were added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by preparative HPLC (chromatography: XBndge prep 21.2 × 150 mm, mobile phase: aqueous solution of acetonitrile-10 mmol / L ammonium bicarbonate, gradient: 52-95%, retention time: 10 min) to obtain compound 28. 1 H NMR (400 MHz, DMSO-d6) δ 7.04-6.84 (m, 1H), 6.92-6.84 (m, 2H), 6.50-6.43 (m, 2H), 4.95-4.86 (m, 2H), 4.63-4.55 (m, 2H), 4.23-4.18 (m, 2H), 3.37-3.31 (m, 2H), 2.75-2.69 (m, 2H), 2.43 (s, 3H), 2.27-2.21 (m, 3H), 1.93-1.86 (m, 2H). ESI-MS theoretical calculation value: C 20 H 24 N3O [M+H] + = 322.2, measured value: 322.1.

[1168] Example 29 Synthesis pathway:

[1169] [ka]

[1170] Step 1 Compound 29-1 (100 mg, 0.92 mmol) and intermediate A (361 mg, 1.39 mmol) were dissolved in tetrahydrofuran (5 mL), DIEA (359 mg, 2.77 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Then HATU (527 mg, 1.39 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain the target compound as a crude product, which was purified by preparative HPLC (chromatography: Waters-Xbridge-C18, 10 μm, 19 × 250 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 24-54%, retention time: 9 min) to obtain compound 29. 1 H NMR (400 MHz, DMSO-d6) δ 8.62-8.41 (m, 2H), 8.21 (d, J = 5.66 Hz, 1H), 7.79-7.72 (m, 1H), 7.26 (dd, J = 7.72, 4.86 Hz, 2H), 6.71 (d, J = 2.28 Hz, 1H), 6.53 (dd, J = 5.68, 2.28 Hz, 1H), 4.36 (d, J = 5.92 Hz, 2H), 4.13 (t, J = 8.25 Hz, 2H), 3.75-3.70 (m, 2H), 3.11-3.05 (m, 1H), 2.64-2.59 (m, 2H). ESI-MS theoretical calculation value: C 17 H 18 F3N4O [M+H] + = 351.1, measured value: 351.2.

[1171] Example 30 Synthesis pathway:

[1172] [ka]

[1173] Step 1 Compound 30-1 (100 mg, 0.82 mmol) and intermediate A (320 mg, 1.23 mmol) were dissolved in tetrahydrofuran (5 mL), DIEA (317 mg, 2.46 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Then, HATU (467 mg, 1.23 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain the crude product of the target compound, which was purified by preparative HPLC (chromatography: Waters-Xbridge-C18, 10 μm, 19 × 250 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 21-51%, retention time: 9.5 min) to obtain compound 30. 1 H NMR (400 MHz, DMSO-d6) δ 9.52 (s, 1H), 8.33 (s, 1H), 8.22 (d, J = 5.66 Hz, 1H), 7.12 (s, 1H), 6.74 (d, J = 2.28 Hz, 1H), 6.55 (dd, J = 5.68, 2.28 Hz, 1H), 4.21-4.13 (m, 2H), 3.80-3.73 (m, 2H), 3.18-3.10 (m, 1H), 2.81-2.75 (m, 2H), 2.40 (s, 3H), 2.16 (s, 3H). Theoretical calculation value of ESI-MS: C 18 H 20 F3N4O [M+H] + = 365.2, measured value: 365.1.

[1174] Example 31 Synthesis pathway:

[1175] [ka]

[1176] Step 1 31-1 (300 mg, 2.22 mmol) was dissolved in tetrahydrofuran (5 mL), and sodium hydride (60%, 54 mg, 2.22 mmol) was slowly added under the protection of nitrogen gas, and the mixture was stirred at room temperature for 1 hour. Ethyl bromoethyl (445 mg, 2.66 mmol) was added dropwise to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water (15 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 7 / 3, v / v) to obtain 31-2. Theoretical calculation value of ESI-MS: C 12 H 16 NO3 [M+H] + = 222.1, Measured value: 222.0.

[1177] Step 2 31-2 (280 mg, 1.27 mmol) was dissolved in tetrahydrofuran (5 mL) and water (1 mL), lithium hydroxide monohydrate (159 mg, 3.80 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The pH of the reaction solution was adjusted to 3 with dilute hydrochloric acid (1 mol / L), a solid precipitated, and the mixture was filtered to obtain 31-3.

[1178] Step 3 Compound 31-3 (100 mg, 0.52 mmol) and intermediate B (77 mg, 0.52 mmol) were dissolved in tetrahydrofuran (3 mL), DIEA (67 mg, 1.56 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Then HATU (197 mg, 0.52 mmol) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by preparative HPLC (chromatography: Waters-SunFire-C18, 10 μm, 19 × 250 mm, mobile phase: acetonitrile-0.1% formic acid aqueous solution, gradient: 20-50%, retention time: 8 min) to obtain compound 31. 1H NMR (400 MHz, DMSO-d6) δ 7.05-7.01 (m, 1H), 6.72-6.59 (m, 3H), 6.54-6.47 (m, 1H), 4.94-4.88 (m, 2H), 4.62-4.56 (m, 2H), 4.30-4.16 (m, 4H), 3.47-3.42 (m, 2H), 2.44 (s, 3H), 2.24 (s, 3H). ESI-MS theoretical calculation value: C 19 H 22 N3O2[M+H] + = 324.2, measured value: 324.2.

[1179] Example 32 Synthesis pathway:

[1180] [ka]

[1181] Step 1 Compound 32-1 (100 mg, 0.82 mmol) and intermediate A (320 mg, 1.23 mmol) were dissolved in tetrahydrofuran (5 mL), DIEA (317 mg, 2.46 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Then HATU (467 mg, 1.23 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by preparative HPLC (chromatography: Welch-Xtimate-C18, 7 μm, 21.2 × 150 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 27-57%, retention time: 8 min) to obtain compound 32. 1H NMR (400 MHz, DMSO-d6) δ 9.97 (s, 1H), 8.21 (d, J = 5.64 Hz, 1H), 8.06 (d, J = 2.24 Hz, 1H), 7.48 (d, J = 2.22 Hz, 1H), 6.73 (d, J = 2.28 Hz, 1H), 6.56-6.52 (m, 1H), 4.18-4.11 (m, 2H), 3.78-3.72 (m, 2H), 3.16-3.07 (m, 1H), 2.74 (d, J = 7.74 Hz, 2H), 2.25 (s, 3H), 2.09 (s, 3H). ESI-MS theoretical calculation value: C 18 H 20 F3N4O [M+H] + = 365.2, measured value: 365.1.

[1182] Example 33 Synthesis pathway:

[1183] [ka]

[1184] Step 1 Intermediate K (150 mg, 0.89 mmol) and intermediate A (331 mg, 0.89 mmol) were dissolved in DMF (2 mL), TEA (451 mg, 4.46 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Then HATU (407 mg, 1.07 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was diluted with water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. The reaction mixture was then concentrated under reduced pressure to obtain a crude product containing the target compound, and purified by preparative HPLC (chromatography: XBndge C18, 10 μm, 19 × 250 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 25-45%, retention time: 8.5 min) to obtain compound 33. 1H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 5.72 Hz, 1H), 6.71 (d, J = 2.24 Hz, 1H), 6.53 (dd, J = 5.72, 2.22 Hz, 1H), 4.86-4.67 (m, 2H), 4.62-4.46 (m, 2H), 4.21-4.14 (m, 2H), 3.72-3.68 (m, 2H), 3.33-3.25 (m, 1H), 3.19-3.06 (m, 1H), 2.84-2.80 (m, 2H), 1.35-1.31 (m, 6H). ESI-MS theoretical calculation value: C 19 H 22 F3N4OS [M+H] + = 411.1, measured value: 411.1.

[1185] Example 34 Synthesis pathway:

[1186] [ka]

[1187] Step 1 Intermediate L (120 mg, 0.78 mmol) and intermediate A (289 mg, 0.78 mmol) were dissolved in DMF (2 mL), TEA (276 mg, 2.72 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Then HATU (355 mg, 0.93 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was diluted with water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. This crude product was purified by preparative HPLC (chromatography: XBndge C18, 10 μm, 19 × 250 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 30-45%, retention time: 9.5 min) to obtain compound 34. 1H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 5.66 Hz, 1H), 6.71 (d, J = 2.32 Hz, 1H), 6.53 (dd, J = 5.72, 2.28 Hz, 1H), 4.83-4.67 (m, 2H), 4.59-4.43 (m, 2H), 4.21-4.15 (m, 2H), 3.74-3.64 (m, 2H), 3.15-3.08 (m, 1H), 3.04-2.97 (m, 2H), 2.85-2.79 (m, 2H), 1.30 (t, J =7.52 Hz, 3H). ESI-MS theoretical calculation value: C 18 H 20 F3N4OS [M+H] + = 397.1, Measured value: 397.1.

[1188] Example 35 Synthesis pathway:

[1189] [ka]

[1190] Step 1 Compound 35-1 (100 mg, 0.60 mmol) was dissolved in dioxane (5 mL), sodium hydride (60%, 24.0 mg, 0.60 mmol) was added, and the mixture was stirred at room temperature for 10 minutes. Then, intermediate M (240 mg, 0.60 mmol) was added, and the mixture was stirred at room temperature for 4 hours. After the reaction was complete, the mixture was diluted with water (3 mL), concentrated under reduced pressure to obtain a crude product containing the target compound, and purified by preparative HPLC (chromatography: Pntulips BP-C18, 5 μm, 21.2 × 150 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 47-57%, retention time: 9 min) to obtain compound 35. 1H NMR (400 MHz, DMSO-d6) δ 8.23-8.20 (m, 1H), 7.74-7.64 (m, 2H), 7.58-7.52 (m, 1H), 6.69 (d, J = 2.30 Hz, 1H), 6.54-6.50 (m, 1H), 4.51 (s, 2H), 4.12-4.04 (m, 2H), 3.70-3.63 (m, 2H), 3.56-3.51 (m, 2H), 2.78-2.71 (m, 1H), 2.02-1.92 (m, 2H). ESI-MS theoretical calculation value: C 19 H 18 ClF3N3O [M+H] + = 396.1, Measured value: 396.1.

[1191] Example 36 Synthesis pathway:

[1192] [ka]

[1193] Step 1 Compound 36-1 (42 mg, 0.25 mmol) was dissolved in dioxane (5 mL), sodium hydride (60%, 10 mg, 0.25 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Intermediate M (100 mg, 0.25 mmol) was then added, and the mixture was heated to 100°C and stirred for 18 hours. After the reaction was complete, the mixture was diluted with water (3 mL), concentrated under reduced pressure to obtain a crude product containing the target compound, and purified by preparative HPLC (chromatography: Waters-Xbridge-C18, 10 μm, 19 × 250 mm, mobile phase: acetonitrile-10 mmol / L aqueous ammonium bicarbonate solution, gradient: 43-73%, retention time: 9 min) to obtain compound 36. 1H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 5.66 Hz, 1H), 7.68 (d, J = 1.34 Hz, 1H), 7.65 (t, J = 1.75 Hz, 2H), 6.70 (d, J = 2.24 Hz, 1H), 6.51 (dd, J = 5.64, 2.24 Hz, 1H), 4.51 (s, 2H), 4.12-4.03 (m, 2H), 3.71-3.64 (m, 2H), 3.57-3.50 (m, 2H), 2.78-2.72 (m, 1H), 1.98-1.92 (m, 2H). ESI-MS theoretical calculation value: C 19 H 18 ClF3N3O [M+H] + = 396.1, Measured value: 396.1.

[1194] Example 37 Synthesis pathway:

[1195] [ka]

[1196] Step 1 Compound 37-1 (100 mg, 0.60 mmol) was dissolved in dioxane (5 mL), sodium hydride (60%, 24.0 mg, 0.60 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Then, intermediate M (240 mg, 0.60 mmol) was added, and the mixture was heated to 100 °C and stirred for 18 hours. After the reaction was complete, the mixture was diluted with water (3 mL), concentrated under reduced pressure to obtain a crude product containing the target compound, and purified by preparative HPLC (chromatography: Waters-Xbridge-C18, 10 μm, 19 × 250 mm, mo...

Claims

1. A compound represented by formula I or a pharmaceutically acceptable salt thereof. 【Chemistry 1】 (however, 【Chemistry 2】 teeth, 【Transformation 3】 And, m is a natural number between 0 and 3. n is a natural number between 0 and 3, and m and n are not both 0 at the same time. k is a natural number between 0 and 3. X １ , X ２ , X ３ , X ４ and X ５ , independently -CR １ -, N, O, S, 【Chemistry 4】 or chemical bond, R Ｎ－１ is hydrogen, C １ to C ６ alkyl, C １ to C ６ alkoxy or 3- to 7-membered cycloalkyl, where the C １ to C ６ alkyl and C １ to C ６ alkoxy are each independently optionally substituted by one, two, three or four R Ｎ－２ ; Each R Ｎ－２ It is independently a halogen, Y and Z are independently carbonyl (CO) and -(CR ２ R ３ ) ｒ - or a chemical bond, where r is a natural number from 0 to 5. Each W independently has carbonyl (CO), -O-, and -(CR ４ R ５ ) -, -NR ６ - or a chemical bond, Each R １ These are independently hydrogen, halogen, cyano, hydroxyl, and C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, C １ ~C ６ Alkylthio, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl or -NR １－１ R １－２ And here, C １ ~C ６ Alkylthio, C １ ~C ６ Alkyl and C １ ~C ６ Alkoxy can independently have one, two, three, or four R ａ It is optionally replaced by, or two R １ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. Each R ａ These are independently halogen, cyano, hydroxy, and C １ ~C ３ Alkyl, C １ ~C ６ Alkoxy or -NR １－４ R １－５ And, or, two R's ａ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. R １－１ and R １－２ These are independently hydrogen or C １ ~C ６ It is alkyl, and here, C １ ~C ６ Alkyl groups may independently have one, two, three, or four R groups. ｂ It is optionally replaced by R １－１ and R １－２ These atoms form a 3- to 7-membered heterocycloalkyl group with the atoms linked to them, where the 3- to 7-membered heterocycloalkyl group has one, two, three, or four R atoms. ｂ－２ Replaced by choice, Each R ｂ These are independently halogen, cyano, hydroxy, and C １ ~C ６ Alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, C １ ~C ３ Alkyl and NR １－１－１ R １－２－１ Here, the 3-7 member cycloalkyl, 3-7 member heterocycloalkyl and C １ ~C ３ Alkyl groups may independently have one, two, three, or four R groups. ｂ－１ Replaced by choice, Each R ｂ－１ These are independently halogens, hydroxyls, or cyanos. Each R ｂ－２ These are halogens and C １ ~C ６ Alkyl or cyano, R １－４ and R １－５ These are independently hydrogen or C １ ~C ３ It is alkyl, and here, C １ ~C ３ Alkyl groups may independently have one, two, three, or four R groups. １－４－１ It is optionally replaced by R １－４ and R １－５ These atoms form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. R １－１－１ and R １－２－１ These are independently hydrogen or C １ ~C ３ It is alkyl, and here, C １ ~C ３ Alkyl groups may independently have one, two, three, or four R groups. １－１－１－１ Replaced by choice, Each R １－４－１ and R １－１－１－１ is independently halogen, hydroxy or cyano, R ２ and R ３ are each independently hydrogen, halogen, cyano, hydroxy, C １ to C ６ alkoxy or NR ２－１ R ２－２ ; or R ２ and R ３ together with the atoms to which they are attached form a 3- to 7-membered cycloalkyl or 3- to 7-membered heterocycloalkyl, R ２－１ and R ２－２ These are independently hydrogen or C １ ~C ６ It is alkyl, and here, C １ ~C ６ Alkyl groups may independently have one, two, three, or four R groups. ｄ It is optionally replaced by R ２－１ and R ２－２ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. Each R ｄ These are independently halogen, cyano, hydroxy, and C １ ~C ６ Alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl or C １ ~C ３ It is alkyl, R ４ , R ５ and R ６ These are independently hydrogen, halogen, cyano, hydroxyl, and C １ ~C ６ Alkoxy, C １ ~C ６ Alkyl or NR ４－１ R ４－２ And here, C １ ~C ６ Alkyl groups may independently have one, two, three, or four R groups. ｅ Replaced by choice, Each R ｅ These are independently halogen, cyano, hydroxy, and C １ ~C ３ Alkyl, C １ ~C ３ Alkoxy or -NR ４－４ R ４－５ And, R ４－１ and R ４－２ These are independently hydrogen or C １ ~C ６ It is alkyl, and here, C １ ~C ６ Alkyl groups may independently have one, two, three, or four R groups. ｆ It is optionally replaced by R ４－１ and R ４－２ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. Each R ｆ These are independently halogen, cyano, hydroxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, and C １ ~C ３ Alkyl, C １ ~C ３ Alkoxy or -NR ４－１－１ R ４－２－１ And, R ４－４ and R ４－５ These are independently hydrogen or C １ ~C ３ It is alkyl, or R ４ and R ５ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. R ４－１－１ and R ４－２－１ These are independently hydrogen or C １ ~C ３ It is alkyl, L is 【Transformation 5】 And, t is a natural number between 0 and 3. u is a natural number between 0 and 3. E is carbonyl, 【Transformation 6】 , -NHCO-, or a chemical bond, F is carbonyl, 【Transformation 7】 , -O-, -NH- or chemical bond, R ８ and R ９ These are independently hydrogen, halogen, cyano, hydroxy, or C １ ~C ６ It is alkyl, and here, C １ ~C ６ Alkyl groups may independently have one, two, three, or four R groups. ｇ It is optionally replaced by R ８ and R ９ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. Each R ｇ These are independently halogen, cyano, hydroxy, and C １ ~C ３ Alkyl or C １ ~C ３ It is an alkoxy, B is a 3-7 member cycloalkyl, a 4-6 member heterocycloalkyl, a 6-10 member aryl, or a 5-12 member heteroaryl, where the 3-7 member cycloalkyl, 4-6 member heterocycloalkyl, 6-10 member aryl, and 5-12 member heteroaryl are independently one, two, or three R ｉ Replaced by choice, Each R ｉ These are independently hydrogen, halogen, hydroxyl, and C １ ~C ３ Alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, cyano, -NR １１－１ R １１－２ , -OR １１－３ or -SR １１－４ And here, C １ ~C ３ Alkyl groups may independently have one, two, three, or four R groups. ｉ－１ It is optionally replaced by, or R on two identical atoms. ｉ These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, or two adjacent R ｉ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. Each R ｉ－１ C is independent １ ~C ３ Alkyl, halogen, cyano, or hydroxy, R １１－１ and R １１－２ Hydrogen and C are independent of each other. １ ~C ３ Alkyl, 3-7 membered cycloalkyl, or 3-7 membered heterocycloalkyl, or R １１－１ and R １１－２ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. R １１－３ and R １１－４ C is independent １ ~C ３ Alkyl, 3-7 membered cycloalkyl, or 3-7 membered heterocycloalkyl, R １１－１ , R １１－２ , R １１－３ and R １１－４ In the case of C １ ~C ３ Alkyl, 3- to 7-membered cycloalkyl, and 3- to 7-membered heterocycloalkyl groups may independently have one, two, or three R groups. ｉ－２ Replaced by choice, Each R ｉ－２ C is independent １ ~C ３ Alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, halogen, cyano or hydroxy, D stands for hydrogen, halogen, cyano, hydroxy, C １ ~C ６ Alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, 6-10 membered aryl, or 5-12 membered heteroaryl, where C １ ~C ６ Alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, 6-10 membered aryl, and 5-12 membered heteroaryl groups independently contain one, two, or three R groups. ｊ Replaced by choice, Each R ｊ These are independently hydrogen, halogen, cyano, hydroxyl, and C １ ~C ３ Alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, -NR １２－１ R １２－２ , -OR １２－３ or -SR １２－４ And the above C １ ~C ３ Alkyl, 3- to 7-membered cycloalkyl, and 3- to 7-membered heterocycloalkyl groups may independently have one, two, or three R groups. ｋ Replaced by choice, R １２－１ , R １２－２ , R １２－３ and R １２－４ Hydrogen and C are independent of each other. １ ~C ３ Alkyl, 3-7 membered cycloalkyl, or 3-7 membered heterocycloalkyl, where C １ ~C ３ Alkyl, 3- to 7-membered cycloalkyl, and 3- to 7-membered heterocycloalkyl groups may independently have one, two, or three R groups. ｋ－１ It is optionally replaced by R １２－１ and R １２－２ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. Each R ｋ These are independently halogen, cyano, hydroxy, and C １ ~C ３ Alkyl, 3-7 membered cycloalkyl, or 3-7 membered heterocycloalkyl, Each R ｋ－１ These are independently halogen, cyano, hydroxy, and C １ ~C ３ Alkyl, 3-7 membered cycloalkyl, or 3-7 membered heterocycloalkyl, A 【Transformation 8】 X １ , X ２ and X ３ CR １ In that case, the compound represented by formula I is (1) The condition is that E is -NHCO- or a chemical bond, and F is -O-, -NH- or a chemical bond. (2) The condition that E is a carbonyl group and F is -NH-, (3) L is -(CH ２ )-,-(CH ２ ) ２ - 【Chemistry 9】 The condition, (4) If E or F is a carbonyl group, B is a 4-7 member cycloalkyl group, a 6-10 member aryl group, a 5-12 member heteroaryl group, or one, two, or three R groups. ｉ A 4-6 member heterocycloalkyl substituted with, where R on two identical atoms ｉ These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, or two adjacent R ｉ These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl (where the 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl forms a fused ring with B) with the atoms linked to them, where the 4-7 membered cycloalkyl, 6-10 membered aryl, and 5-12 membered heteroaryl independently have one, two, or three R ｉ Conditions that are optionally replaced by, （５） 【Chemistry 10】 teeth, 【Chemistry 11】 And, A 【Chemistry 12】 If X １ , X ２ and X ４ The number of heteroatoms is one or two. A 【Chemistry 13】 And if L is a carbonyl group, then u is a natural number from 1 to 3, B is a 4-6 member heterocycloalkyl group, and the 4-6 member heterocycloalkyl group independently has one, two or three R groups. ｉ Replaced by choice, In the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 5. (Satisfy any one of the following conditions.) 【Request Item 2】 【Chemistry 14】 teeth, 【Chemistry 15】 And, m is a natural number between 0 and 3. n is a natural number between 0 and 3, and m and n are not both 0 at the same time. k is a natural number between 0 and 3. X １ , X ２ , X ３ , X ４ and X ５ , independently -CR １ -, N, O, S, 【Chemistry 16】 or chemical bond, R Ｎ－１ is hydrogen or C １ ~C ６ Alkyl, C １ ~C ６ It is an alkoxy or a 3- to 7-membered cycloalkyl, where the C １ ~C ６ Alkyl and C １ ~C ６ Alkoxy can independently have one, two, three, or four R Ｎ－２ Replaced by choice, Each R Ｎ－２ It is independently a halogen, Y and Z are independently carbonyl (CO) and -(CR ２ R ３ ) ｒ - or a chemical bond, where r is a natural number from 0 to 5. Each W independently has carbonyl (CO), -O-, and -(CR ４ R ５ ) -, -NR ６ - or a chemical bond, Each R １ These are independently hydrogen, halogen, cyano, hydroxyl, and C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl or -NR １－１ R １－２ And here, C １ ~C ６ Alkyl and C １ ~C ６ Alkoxy can independently have one, two, three, or four R ａ It is optionally replaced by, or two R １ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. Each R ａ These are independently halogen, cyano, hydroxy, and C １ ~C ３ Alkyl, C １ ~C ６ Alkoxy or -NR １－４ R １－５ And, or, two R's ａ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. R １－１ and R １－２ These are independently hydrogen or C １ ~C ６ It is alkyl, and here, C １ ~C ６ Alkyl groups may independently have one, two, three, or four R groups. ｂ It is optionally replaced by R １－１ and R １－２ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. Each R ｂ These are independently halogen, cyano, hydroxy, and C １ ~C ６ Alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, C １ ~C ３ Alkyl and NR １－１－１ R １－２－１ Here, the 3-7 member cycloalkyl, 3-7 member heterocycloalkyl and C １ ~C ３ Alkyl groups may independently have one, two, three, or four R groups. ｂ－１ Replaced by choice, Each R ｂ－１ These are independently halogens, hydroxyls, or cyanos. R １－４ and R １－５ These are independently hydrogen or C １ ~C ３ It is alkyl, and here, C １ ~C ３ Alkyl groups may independently have one, two, three, or four R groups. １－４－１ It is optionally replaced by R １－４ and R １－５ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. R １－１－１ and R １－２－１ These are independently hydrogen or C １ ~C ３ It is alkyl, and here, C １ ~C ３ Alkyl groups may independently have one, two, three, or four R groups. １－１－１－１ Replaced by choice, Each R １－４－１ and R １－１－１－１ These are independently halogens, hydroxyls, or cyanos. R ２ and ３ These are independently hydrogen, halogen, cyano, hydroxyl, and C １ ~C ６ Alkoxy or NR ２－１ R ２－２ And, or, R ２ and R ３ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. R ２－１ and R ２－２ These are independently hydrogen or C １ ~C ６ It is alkyl, and here, C １ ~C ６ Alkyl groups may independently have one, two, three, or four R groups. ｄ It is optionally replaced by R ２－１ and R ２－２ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. Each R ｄ These are independently halogen, cyano, hydroxy, and C １ ~C ６ Alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl or C １ ~C ３ It is alkyl, R ４ , R ５ and R ６ These are independently hydrogen, halogen, cyano, hydroxyl, and C １ ~C ６ Alkoxy, C １ ~C ６ Alkyl or NR ４－１ R ４－２ And here, C １ ~C ６ Alkyl groups may independently have one, two, three, or four R groups. ｅ Replaced by choice, Each R ｅ These are independently halogen, cyano, hydroxy, and C １ ~C ３ Alkyl, C １ ~C ３ Alkoxy or -NR ４－４ R ４－５ And, R ４－１ and R ４－２ These are independently hydrogen or C １ ~C ６ It is alkyl, and here, C １ ~C ６ Alkyl groups may independently have one, two, three, or four R groups. ｆ It is optionally replaced by R ４－１ and R ４－２ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. Each R ｆ These are independently halogen, cyano, hydroxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, and C １ ~C ３ Alkyl, C １ ~C ３ Alkoxy or -NR ４－１－１ R ４－２－１ And, R ４－４ and R ４－５ These are independently hydrogen or C １ ~C ３ It is alkyl, or R ４ and R ５ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. R ４－１－１ and R ４－２－ These are independently hydrogen or C １ ~C ３ It is alkyl, L is 【Chemistry 17】 And, t is a natural number between 0 and 3. u is a natural number between 0 and 3. E is a carbonyl, -NHCO-, or chemical bond. F is a carbonyl, -O-, -NH-, or chemical bond. R ８ and R ９ These are independently hydrogen, halogen, cyano, hydroxy, or C １ ~C ６ It is alkyl, and here, C １ ~C ６ Alkyl groups may independently have one, two, three, or four R groups. ｇ It is optionally replaced by R ８ and R ９ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. Each R ｇ These are independently halogen, cyano, hydroxy, and C １ ~C ３ Alkyl or C １ ~C ３ It is an alkoxy, B is a 3-7 member cycloalkyl, a 4-6 member heterocycloalkyl, a 6-10 member aryl, or a 5-12 member heteroaryl, where the 3-7 member cycloalkyl, 4-6 member heterocycloalkyl, 6-10 member aryl, and 5-12 member heteroaryl are independently one, two, or three R ｉ Replaced by choice, Each R ｉ These are independently hydrogen, halogen, hydroxyl, and C １ ~C ３ Alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, cyano, -NR １１－１ R １１－２ , -OR １１－３ or -SR １１－４ And here, C １ ~C ３ Alkyl groups may independently have one, two, three, or four R groups. ｉ－１ It is optionally replaced by, or R on two identical atoms. ｉ These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, or two adjacent R ｉ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. Each R ｉ－１ C is independent １ ~C ３ Alkyl, halogen, cyano, or hydroxy, R １１－１ and R １１－２ Hydrogen and C are independent of each other. １ ~C ３ Alkyl, 3-7 membered cycloalkyl, or 3-7 membered heterocycloalkyl, or R １１－１ and R １１－２ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. R １１－３ and R １１－４ C is independent １ ~C ３ Alkyl, 3-7 membered cycloalkyl, or 3-7 membered heterocycloalkyl, R １１－１ , R １１－２ , R １１－３ and R １１－４ In the case of C １ ~C ３ Alkyl, 3- to 7-membered cycloalkyl, and 3- to 7-membered heterocycloalkyl groups may independently have one, two, or three R groups. ｉ－２ Replaced by choice, Each R ｉ－２ C is independent １ ~C ３ Alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, halogen, cyano or hydroxy, D stands for hydrogen, halogen, cyano, hydroxy, C １ ~C ６ Alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, 6-10 membered aryl, or 5-12 membered heteroaryl, where C １ ~C ６ Alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, 6-10 membered aryl, and 5-12 membered heteroaryl groups independently contain one, two, or three R groups. ｊ Replaced by choice, Each R ｊ These are independently hydrogen, halogen, cyano, hydroxyl, and C １ ~C ３ Alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, -NR １２－１ R １２－２ , -OR １２－３ or -SR １２－４ And the above C １ ~C ３ Alkyl, 3- to 7-membered cycloalkyl, and 3- to 7-membered heterocycloalkyl groups may independently have one, two, or three R groups. ｋ Replaced by choice, R １２－１ , R １２－２ , R １２－３ and R １２－４ Hydrogen and C are independent of each other. １ ~C ３ Alkyl, 3-7 membered cycloalkyl, or 3-7 membered heterocycloalkyl, where C １ ~C ３ Alkyl, 3- to 7-membered cycloalkyl, and 3- to 7-membered heterocycloalkyl groups may independently have one, two, or three R groups. ｋ－１ It is optionally replaced by R １２－１ and R １２－２ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. Each R ｋ These are independently halogen, cyano, hydroxy, and C １ ~C ３ Alkyl, 3-7 membered cycloalkyl, or 3-7 membered heterocycloalkyl, Each R ｋ－１ These are independently halogen, cyano, hydroxy, and C １ ~C ３ Alkyl, 3-7 membered cycloalkyl, or 3-7 membered heterocycloalkyl, A [Chemistry 18] X １ , X ２ and X ３ CR １ In that case, the compound represented by formula I is (1) The condition is that E is -NHCO- or a chemical bond, and F is -O-, -NH- or a chemical bond. (2) The condition that E is a carbonyl group and F is -NH-, (3) L is -(CH ２ )-,-(CH ２ ) ２ - 【Chemistry 19】 The condition, (4) If E or F is a carbonyl group, B is a 4-7 member cycloalkyl group, a 6-10 member aryl group, a 5-12 member heteroaryl group, or one, two, or three R groups. ｉ A 4-6 member heterocycloalkyl substituted with, where R on two identical atoms ｉ These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, or two adjacent R ｉ This forms a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl, where the 4-7 membered cycloalkyl, 6-10 membered aryl, and 5-12 membered heteroaryl independently have one, two, or three R ｉ Replaced by choice, （５） 【Chemistry 20】 teeth, 【Chemistry 21】 And, A 【Chemistry 22】 If X １ , X ２ and X ４ The number of heteroatoms is one or two. A 【Chemistry 23】 And if L is a carbonyl group, then u is a natural number from 1 to 3, B is a 4-6 member heterocycloalkyl group, and the 4-6 member heterocycloalkyl group independently has one, two or three R groups. ｉ Replaced by choice, In the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl, the heteroatoms are N, O, or S, and the number of heteroatoms is 1 to 5; or, in the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 5. A compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that it satisfies any one of the following conditions.

3. (1) R Ｎ－１ In the case of C １ ~C ６ Alkyl is C １ ~C ３ It is alkyl, for example, methyl, ethyl, n-propyl or isopropyl, and also, for example, methyl, ethyl or isopropyl, (2) R Ｎ－１ In the case of C １ ~C ６ Alkoxy is C １ ~C ３ The condition is that it is an alkoxy, for example, methoxy, ethoxy, n-propoxy, or isopropoxy, (3) Caution Ｎ－１ In this case, the 3- to 7-membered cycloalkyl group is a 3- to 6-membered cycloalkyl group, for example, cyclopropyl, cyclobutyl, or cyclopentyl. (4) R Ｎ－２ In this case, the halogen is F, Cl, Br, or I, for example, under the condition that it is F or Cl, (5) Note １ In this case, the halogen is F, Cl, Br, or I, for example, F or Cl, and also, for example, Cl. (6) R １ In the case of C １ ~C ６ Alkyl is C １ ~C ３ It is alkyl, for example, methyl, ethyl, n-propyl or isopropyl, and also, for example, methyl, ethyl or isopropyl, (7) R １ In the case of C １ ~C ６ Alkoxy is C １ ~C ３ It is an alkoxy, for example, methoxy, ethoxy, n-propoxy or isopropoxy, and also, for example, methoxy or ethoxy, (8) R １ In this case, the 3- to 7-membered cycloalkyl is a 3- to 6-membered cycloalkyl, for example, cyclopropyl, cyclobutyl, or cyclopentyl, and also, for example, cyclopropyl. (9) Caution １ In this, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatom of the 3- to 6-membered heterocycloalkyl is preferably N or O, the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two, and the 3- to 6-membered heterocycloalkyl is more preferably a 4-membered heterocycloalkyl, for example, 【Chemistry 24】 The condition, (10) R ａ In this case, the halogen is F, Cl, Br, or I, for example, F or Cl, and also, for example, F. (11) R ａ In the case of C １ ~C ３ The alkyl group is methyl, ethyl, n-propyl, or isopropyl. (12) R ａ In the case of C １ ~C ６ Alkoxy is C １ ~C ３ It is an alkoxy, for example, methoxy, ethoxy, n-propoxy or isopropoxy, and also, for example, methoxy, (13) R ａ In this, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatom of the 3- to 6-membered heterocycloalkyl is preferably N or O, the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two, and the 3- to 6-membered heterocycloalkyl is more preferably a 4-membered heterocycloalkyl, for example, 【Chemistry 25】 The condition, (14) R ａ In this case, the 3- to 7-membered cycloalkyl group is a 3- to 6-membered cycloalkyl group, for example, cyclopropyl, cyclobutyl, or cyclopentyl. (15) R １－１ and R １－２ In the case of C １ ~C ６ Alkyl is C １ ~C ３ The alkyl group is, for example, methyl, ethyl, n-propyl, or isopropyl, and also, for example, methyl or ethyl, preferably methyl. (16) R １－１ and R １－２ In this, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatom of the 3- to 6-membered heterocycloalkyl is preferably N or O, the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two, the 3- to 6-membered heterocycloalkyl is, for example, a 4-membered heterocycloalkyl, and also, for example, 【Chemistry 26】 The condition, (17) R ｂ In this case, the halogen is F, Cl, Br, or I, for example, under the condition that it is F or Cl, (18) R ｂ In the case of C １ ~C ６ Alkoxy is C １ ~C ３ The condition is that it is an alkoxy, for example, methoxy, ethoxy, n-propoxy, or isopropoxy, (19) R ｂ In this case, the 3- to 7-membered cycloalkyl is a 3- to 6-membered cycloalkyl, for example, cyclopropyl, cyclobutyl, or cyclopentyl, and also, for example, cyclopropyl. (20) R ｂ In this case, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatoms of the 3- to 6-membered heterocycloalkyl are preferably N or O, and the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two. (21) R ｂ In the case of C １ ~C ３ The alkyl group is preferably methyl, ethyl, n-propyl, or isopropyl, for example, under the condition that it is methyl. (22) R ｂ－１ In this case, the halogen is F, Cl, Br, or I, for example, under the condition that it is F or Cl, (23) R １－４ and R １－５ In the case of C １ ~C ３ Alkyl is methyl, ethyl, n-propyl, or isopropyl, for example, methyl, ethyl, or n-propyl, and also, for example, methyl. (24) R １－４ and R １－５ In this, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatom of the 3- to 6-membered heterocycloalkyl is preferably N or O, the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two, and the 3- to 6-membered heterocycloalkyl is more preferably a 4-membered heterocycloalkyl, for example, 【Chemistry 27】 The condition, (25) R １－１－１ and R １－２－１ In the case of C １ ~C ３ Alkyl compounds are methyl, ethyl, n-propyl, or isopropyl. (26) R １－４－１ and R １－１－１－１ In this case, the halogen is F, Cl, Br, or I, for example, F or Cl, and also, for example, F. (27) R ２ and R ３ In this case, the halogen is F, Cl, Br, or I, for example, under the condition that it is F or Cl, (28) R ２ and R ３ In the case of C １ ~C ６ Alkoxy is C １ ~C ３ The condition is that it is an alkoxy, for example, methoxy, ethoxy, n-propoxy, or isopropoxy, (29) R ２ and R ３ In this case, the 3- to 7-membered cycloalkyl group is a 3- to 6-membered cycloalkyl group, for example, cyclopropyl, cyclobutyl, or cyclopentyl. (30) R ２ and R ３ In this case, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatoms of the 3- to 6-membered heterocycloalkyl are preferably N or O, and the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two. (31) R ２－１ and R ２－２ In the case of C １ ~C ６ Alkyl is C １ ~C ３ It is alkyl, for example, methyl, ethyl, n-propyl or isopropyl, and also, for example, methyl or ethyl, (32) R ２－１ and R ２－２ In this case, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatoms of the 3- to 6-membered heterocycloalkyl are preferably N or O, and the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two. (33) Caution ｄ In this case, the halogen is F, Cl, Br, or I, for example, under the condition that it is F or Cl, (34) R ｄ In the case of C １ ~C ６ Alkoxy is C １ ~C ３ The condition is that it is an alkoxy, for example, methoxy, ethoxy, n-propoxy, or isopropoxy, (35) Caution ｄ In this case, the 3- to 7-membered cycloalkyl group is a 3- to 6-membered cycloalkyl group, for example, cyclopropyl, cyclobutyl, or cyclopentyl. (36) R ｄ In this case, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatoms of the 3- to 6-membered heterocycloalkyl are preferably N or O, and the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two. (37) R ｄ In the case of C １ ~C ３ The alkyl group is methyl, ethyl, n-propyl, or isopropyl. (38) R ４ , R ５ and R ６ In this case, the halogen is F, Cl, Br, or I, for example, under the condition that it is F or Cl, (39) Caution ４ , R ５ and R ６ In the case of C １ ~C ６ Alkoxy is C １ ~C ３ The condition is that it is an alkoxy, for example, methoxy, ethoxy, n-propoxy, or isopropoxy, (40) R ４ , R ５ and R ６ In the case of C １ ~C ６ Alkyl is C １ ~C ３ The condition is that it is alkyl, for example, methyl, ethyl, n-propyl, or isopropyl, (41) R ｅ In this case, the halogen is F, Cl, Br, or I, for example, under the condition that it is F or Cl, (42) R ｅ In the case of C １ ~C ３ The alkyl group is methyl, ethyl, n-propyl, or isopropyl. (43) R ｅ In the case of C １ ~C ３ The alkoxy is methoxy, ethoxy, n-propoxy, or isopropoxy, (44) R ４－１ and R ４－２ In the case of C １ ~C ６ Alkyl is C １ ~C ３ The condition is that it is alkyl, for example, methyl, ethyl, n-propyl, or isopropyl, (45) R ４－１ and R ４－２ In this case, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatoms of the 3- to 6-membered heterocycloalkyl are preferably N or O, and the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two. (46) R ｆ In this case, the halogen is F, Cl, Br, or I, for example, under the condition that it is F or Cl, (47) R ｆ In this case, the 3- to 7-membered cycloalkyl group is a 3- to 6-membered cycloalkyl group, for example, cyclopropyl, cyclobutyl, or cyclopentyl. (48) R ｆ In this case, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatoms of the 3- to 6-membered heterocycloalkyl are preferably N or O, and the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two. (49) R ｆ In the case of C １ ~C ３ The alkyl group is methyl, ethyl, n-propyl, or isopropyl. (50) R ｆ In the case of C １ ~C ３ The alkoxy is methoxy, ethoxy, n-propoxy, or isopropoxy, (51) R ４－４ and R ４－５ In the case of C １ ~C ３ The alkyl group is methyl, ethyl, n-propyl, or isopropyl. (52) t is a natural number between 0 and 3, for example, 0, 1, 2 or 3, and furthermore, for example, the condition that 0, 1 or 2, (53) u is a natural number between 0 and 3, for example, 0, 1, 2 or 3, and furthermore, for example, the condition that 0, 1 or 2, (54) R ８ and R ９ In this case, the halogen is F, Cl, Br, or I, for example, under the condition that it is F or Cl, (55) R ８ and R ９ In the case of C １ ~C ６ Alkyl is C １ ~C ３ It is alkyl, for example, methyl, ethyl, n-propyl or isopropyl, and also, for example, methyl, (56) R ８ and R ９ In this case, the 3- to 7-membered cycloalkyl is a 3- to 6-membered cycloalkyl, for example, cyclopropyl, cyclobutyl, or cyclopentyl, and also, for example, cyclopropyl. (57) R ８ and R ９ In this case, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatom of the 3- to 6-membered heterocycloalkyl is preferably N or O, the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two, and the 3- to 6-membered heterocycloalkyl is, for example, a 4-membered heterocycloalkyl, and also, for example, an oxetane. (58) R ｇ In this case, the halogen is F, Cl, Br, or I, for example, under the condition that it is F or Cl, (59) Caution ｇ In the case of C １ ~C ３ Alkyl is methyl, ethyl, n-propyl, or isopropyl, for example, under the condition that it is methyl, (60) R ｇ In the case of C １ ~C ３ The alkoxy is methoxy, ethoxy, n-propoxy, or isopropoxy, (61) In B, the 3- to 7-membered cycloalkyl is a 3- to 6-membered cycloalkyl, for example, cyclopropyl, cyclobutyl, or cyclopentyl. (62) In B, the 4- to 7-membered cycloalkyl is a 3- to 6-membered cycloalkyl, for example, cyclobutyl or cyclopentyl. (63) In B, the 4- to 6-membered heterocycloalkyl is a 4-membered heterocycloalkyl, a 5-membered heterocycloalkyl, or a 6-membered heterocycloalkyl, and the heteroatoms of the 4-membered heterocycloalkyl, 5-membered heterocycloalkyl, and 6-membered heterocycloalkyl are preferably N, and the number of heteroatoms of the 4- to 6-membered heterocycloalkyl is preferably one or two, for example, the 4- to 6-membered heterocycloalkyl is a 4-membered azacycloalkyl or a 5-membered azacycloalkyl, and the 4-membered azacycloalkyl is 【Chemistry 28】 The 5-membered azacycloalkyl may be, 【Chemistry 29】 Good conditions, (64) In B, the 6-10 member aryl is phenyl or naphthyl, for example, under the condition that it is phenyl, (65) R ｉ In this case, the halogen is F, Cl, Br, or I, for example, F or Cl, and also, for example, F. (66) R ｉ In the case of C １ ~C ３ Alkyl is methyl, ethyl, n-propyl, or isopropyl, and also, for example, under the condition that it is methyl, (67) R ｉ In this case, the 3- to 7-membered cycloalkyl is a 3- to 6-membered cycloalkyl, for example, cyclopropyl, cyclobutyl, or cyclopentyl, and also, for example, cyclopropyl or cyclobutyl, and for example, cyclopropyl. (68) R ｉ In this case, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatoms of the 3- to 6-membered heterocycloalkyl are preferably N or O, and the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two. (69) R ｉ－１ In this case, the halogen is F, Cl, Br, or I, for example, under the condition that it is F or Cl, (70) R ｉ－１ In the case of C １ ~C ３ The alkyl group is ethyl, n-propyl, or isopropyl. (71) R １１－１ , R １１－２ , R １１－３ and R １１－４ In the case of C １ ~C ３ The alkyl group is methyl, ethyl, n-propyl, or isopropyl. (72) R １１－３ and R １１－４ In this case, the 3- to 7-membered cycloalkyl group is a 3- to 6-membered cycloalkyl group, for example, cyclopropyl, cyclobutyl, or cyclopentyl. (73) R １１－３ and R １１－４ In this case, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatoms of the 3- to 6-membered heterocycloalkyl are preferably N or O, and the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two. (74) R １１－１ and R １１－２ In this case, the 3- to 7-membered cycloalkyl group is a 3- to 6-membered cycloalkyl group, for example, cyclopropyl, cyclobutyl, or cyclopentyl. (75) R １１－１ and R １１－２ In this case, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatoms of the 3- to 6-membered heterocycloalkyl are preferably N or O, and the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two. (76) R ｉ－２ In this case, the halogen is F, Cl, Br, or I, for example, under the condition that it is F or Cl, (77) R ｉ－２ In the case of C １ ~C ３ The alkyl group is methyl, ethyl, n-propyl, or isopropyl. (78) R ｉ－２ In this case, the 3- to 7-membered cycloalkyl group is a 3- to 6-membered cycloalkyl group, for example, cyclopropyl, cyclobutyl, or cyclopentyl. (79) R ｉ－２ In this case, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatoms of the 3- to 6-membered heterocycloalkyl are preferably N or O, and the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two. (80) In D, the halogen is F, Cl, Br or I, for example, under the condition that it is F or Cl, (81) In D, the C １ ~C ６ Alkyl is C １ ~C ３ It is alkyl, for example, methyl, ethyl, n-propyl or isopropyl, and also, for example, methyl, (82) In D, the 3- to 7-membered cycloalkyl is a 3- to 6-membered cycloalkyl, for example, cyclopropyl, cyclobutyl, or cyclopentyl, for example, cyclopropyl. (83) In D, the 6-10 member aryl is phenyl or naphthyl, (84) R ｊ In this case, the halogen is F, Cl, Br, or I, for example, F or Cl, and also, for example, F. (85) R ｊ In the case of C １ ~C ３ Alkyl is methyl, ethyl, n-propyl, or isopropyl, for example, methyl, ethyl, or isopropyl, and also, for example, methyl. (86) R ｊ In this case, the 3- to 7-membered cycloalkyl is a 3- to 6-membered cycloalkyl, for example, cyclopropyl, cyclobutyl, or cyclopentyl, and also, for example, cyclopropyl. (87) R ｊ In this case, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatoms of the 3- to 6-membered heterocycloalkyl are preferably N or O, and the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two. (88) R １２－１ , R １２－２ , R １２－３ and R １２－４ In the case of C １ ~C ３ Alkyl is methyl, ethyl, n-propyl, or isopropyl, for example, under the condition that it is methyl or ethyl, (89) R １２－１ , R １２－２ , R １２－３ and R １２－４ In this case, the 3- to 7-membered cycloalkyl group is a 3- to 6-membered cycloalkyl group, for example, cyclopropyl, cyclobutyl, or cyclopentyl. (90) R １２－１ , R １２－２ , R １２－３ and R １２－４ In this case, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatoms of the 3- to 6-membered heterocycloalkyl are preferably N or O, and the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two. (91) R ｋ In this case, the halogen is F, Cl, Br, or I, for example, F or Cl, and also, for example, F. (92) R ｋ In the case of C １ ~C ３ The alkyl group is methyl, ethyl, n-propyl, or isopropyl. (93) Caution ｋ In this case, the 3- to 7-membered cycloalkyl group is a 3- to 6-membered cycloalkyl group, for example, cyclopropyl, cyclobutyl, or cyclopentyl. (94) R ｋ In this case, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatoms of the 3- to 6-membered heterocycloalkyl are preferably N or O, and the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two. (95) Caution ｋ－１ In this case, the halogen is F, Cl, Br, or I, for example, F or Cl, and also, for example, F. (96) R ｋ－１ In the case of C １ ~C ３ Alkyl is methyl, ethyl, n-propyl, or isopropyl, for example, under the condition that it is methyl, (97) R ｋ－１ In this case, the 3- to 7-membered cycloalkyl group is a 3- to 6-membered cycloalkyl group, for example, cyclopropyl, cyclobutyl, or cyclopentyl. (98) R ｋ－１ In this case, the 3- to 7-membered heterocycloalkyl is a 3- to 6-membered heterocycloalkyl, the heteroatoms of the 3- to 6-membered heterocycloalkyl are preferably N or O, and the number of heteroatoms of the 3- to 6-membered heterocycloalkyl is preferably one or two. (99) Caution １ In the case of C １ ~C ６ The alkylthio is preferably C １ ~C ３ It is an alkylthio, for example, methylthio, ethylthio, n-propylthio or isopropylthio, and also, for example, methylthio, (100)R ｂ－２ In this case, the halogen is preferably F, Cl, Br, or I, for example, under the condition that it is F, (101) R ｂ－２ In the case of C １ ~C ６ The alkyl is preferably C １ ~C ３ It is alkyl, for example, methyl, ethyl, n-propyl or isopropyl, and also, for example, methyl, A compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that it satisfies any one of the following conditions.

4. (1) m is a natural number between 0 and 3, for example, 0, 1, 2 or 3, and furthermore, for example, the condition that 1, 2 or 3 (2) n is a natural number between 0 and 3, for example, 1, 2, or 3, and also, for example, the condition that n is 1 or 2, (3) k is a natural number between 0 and 3, for example, 0, 1, 2 or 3, and also, for example, the condition that k is 1, 2 or 3, (4) The condition that r is a natural number between 0 and 5, for example, 0, 1, 2, 3, 4 or 5, and also for example, 1 or 2, (5) Note Ｎ－１ C １ ~C ６ Conditions for being alkyl, (6) Each W independently - (CR ４ R ５ )-, -O-, -NR ６ - Or the condition that it is a chemical bond, (7) Y and Z are independently carbonyl (CO) or -(CR ２ R ３ ) ｒ - condition, (8) Each R １ These are hydrogen, halogen, and C, independently. １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl or -NR １－１ R １－２ The condition, (9) Each R ａ These are independently hydroxy, C １ ~C ３ Alkoxy or NR １－４ R １－５ The condition, (10) Each R ｂ These are independently hydroxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, and C １ ~C ３ Alkyl, C １ ~C ３ Alkoxy or NR １－１－１ R １－２－１ The condition, (11) R ｂ－１ The condition is that it is independently hydroxyl. (12) R １－４－１ The condition is that it is a halogen. (13) R ２ and R ３ It is independently hydrogen or NR ２－１ R ２－２ And preferably, R ２ and R ３ The condition is that it is hydrogen independently. (14) R ４ , R ５ and R ６ The condition is that it is hydrogen independently. (15) R ｅ -NR ４－４ R ４－５ The condition, (16) R ４－４ and R ４－５ These are independently hydrogen or C １ ~C ３ Conditions for being alkyl, (17) E is a carbonyl or chemical bond, (18) F is -NH-, -O-, or a chemical bond, (19) R ８ and R ９ These are independently hydrogen or C １ ~C ６ It is alkyl, or R ８ and R ９ These form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, preferably R ８ and R ９ C is independent １ ~C ６ It is alkyl, or R ８ and R ９ The conditions for forming a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, (20) B is a 4-6 member heterocycloalkyl, a 6-10 member aryl, or a 5-12 member heteroaryl, where the 5-12 member heteroaryl, 6-10 member aryl, and 4-6 member heterocycloalkyl are independently one, two, or three R ｉ It is optionally substituted by, preferably, B is a 4-6 member heterocycloalkyl or a 5-12 member heteroaryl, where the 5-12 member heteroaryl and 4-6 member heterocycloalkyl are independently one, two or three R ｉ Replaced by choice, (21) R ｉ is hydrogen, halogen, hydroxyl, or C １ ~C ３ It is alkyl, or two R ｉ The conditions for forming a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, (22) D is hydrogen, C １ ~C ６ It is an alkyl or a 5-12 member heteroaryl, where the C １ ~C ６ Alkyl and 5- to 12-membered heteroaryl groups independently have one, two, or three R groups. ｊ It is optionally substituted by, or D is hydrogen, a 3-7 member cycloalkyl, C １ ~C ６ It is an alkyl or a 5-6 member heteroaryl, where the C １ ~C ６ Alkyl and 5-6 member heteroaryl groups independently have one, two, or three R groups. ｊ Conditions that are optionally replaced by, (23) R ｊ is halogen, C １ ~C ３ Alkyl, OR １２－３ or SR １２－４ And preferably, R ｊ is halogen or C １ ~C ３ Conditions for being alkyl, (24) R １２－３ and R １２－４ C is independent １ ~C ３ Conditions for being alkyl, (25) R ｋ The conditions for being a halogen independently are (26) R ｋ－１ The conditions for being a halogen independently are (27) In the 3-7 member heterocycloalkyl, 5-6 member heteroaryl, 4-6 member heterocycloalkyl and 5-12 member heteroaryl compounds, the heteroatoms are N, O, or S, and the number of heteroatoms is 1 to 3. A compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that it satisfies any one of the following conditions.

5. (1) X １ and X ３ N is independent of X ４ and X ２ , independently -CR １ - and preferably, X １ and X ３ N is independent of X ４ and X ２ CR is independent １ - If so, each R １ C is independent １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, C １ ~C ６ Alkylthio, 3-7 membered heterocycloalkyl or -NR １－１ R １－２ And more preferably, each R １ C is independent １ ~C ６ Alkyl or C １ ~C ６ It is an alkoxy, Or, X ２ and X ３ N is independent of X ４ and X １ , independently -CR １ - and preferably, X ２ and X ３ N is independent of X ４ and X １ CR is independent １ - If this is the case, B is azetidine, and the azetidine is, for example, 【Transformation 30】 and / or X ２ and X ３ N is independent of X ４ and X １ CR is independent １ If -, D is a 6-membered heteroaryl, where the 6-membered heteroaryl is independently one, two or three R ｊ The six-membered heteroaryl is optionally replaced by, for example, 【Chemistry 31】 and / or X ２ and X ３ N is independent of X ４ and X １ CR is independent １ - If so, each R １ C is independent １ ~C ６ Alkyl or 3-7 member heterocycloalkyl, Or, X １ and X ４ N is independent of X ２ and X ３ , independently -CR １ - and preferably, X ２ CR is independent １ - If R １ C １ ~C ６ Alkyl or C １ ~C ６ It is an alkoxy, Or, 【Chemistry 32】 teeth, 【Transformation 33】 Preferably, 【Transformation 34】 but 【Chemistry 35】 If so, each R ｊ OR １２－３ or SR １２－４ And, Alternatively, X １ is N, and X ２ , X ３ and X ４ are -CR １ -, and Y and Z are independently -(CH ２ )-, and preferably, X １ is N, and X ２ , X ３ and X ４ are -CR １ -, and Y and Z are independently -(CH ２ )-, when m and n are 2, R ｊ is trifluoromethyl, and more preferably, R １ is C １ to C ６ alkyl or C １ to C ６ alkoxy under the condition (2) R Ｎ－１ is hydrogen, C １ ~C ６ Conditions: It is alkyl or a 3- to 7-membered cycloalkyl, (3) Each W independently - (CR ４ R ５ ) -, -NR ６ - Or the condition that it is a chemical bond, (4) Each R １ These are hydrogen, halogen, and C, independently. １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, C １ ~C ６ Alkylthio, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl or -NR １－１ R １－２ And here, C １ ~C ６ Alkylthio, C １ ~C ６ Alkyl and C １ ~C ６ Alkoxy can independently have one, two, three, or four R ａ This is replaced by any choice, for example, each R １ Hydrogen and C are independent of each other. １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, C １ ~C ６ Alkylthio, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl or -NR １－１ R １－２ And also, for example, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, C １ ~C ６ Alkylthio or -NR １－１ R １－２ Preferably, each R １ C is independent １ ~C ６ If D is alkyl, and more preferably if D is pyrimidine, then each R １ The conditions are that it is independently a halogen or a 3- to 7-membered cycloalkyl, (5) Note １－１ and R １－２ These are independently hydrogen or C １ ~C ６ It is alkyl, or R １－１ and R １－２ These form 3- to 7-membered heterocycloalkyl groups with atoms linked to them, for example, R １－１ and R １－２ The conditions for forming a 3-7 member heterocycloalkyl group with the atoms linked to them, (6) Each R ａ is independently halogen, hydroxy, C １ ~ C ６ alkoxy or -NR １－４ R １－５ For example, each R ａ is independently hydroxy, C １ ~ C ６ alkoxy or -NR １－４ R １－５ and, for example, the condition of being hydroxy, (7) Each R ｂ These are independently hydroxy, 3- to 7-membered cycloalkyl, or C １ ~C ３ It is alkyl, for example, each R ｂ These are independently hydroxy, 3- to 7-membered cycloalkyl groups, and also, for example, each R ｂ The conditions are that they are independently 3- to 7-membered cycloalkyl groups. (8) Each R ｂ－２ These are, independently, halogen or C １ ~C ６ Conditions for being alkyl, (9) Caution １－４ and R １－５ C is independent １ ~C ３ Conditions for being alkyl, (10) Each R １－４－１ The conditions for being a halogen independently are (11) R ２－１ and R ２－２ These are independently hydrogen or C １ ~C ６ The condition is that it is alkyl, for example, hydrogen, (12) R ４ , R ５ and R ６ It is independently hydrogen or NR ４－１ R ４－２ The condition, (13) R ４－１ and R ４－２ The condition is that it is hydrogen independently. (14) E is carbonyl, 【Transformation 36】 , -NHCO- or a chemical bond, (15) F is carbonyl, 【Chemistry 37】 The conditions are -O-, -NH- or a chemical bond, (16) R ８ and R ９ These are independently hydrogen or C １ ~C ６ It is alkyl, or R ８ and R ９ The conditions for forming a 3-7 membered cycloalkyl group with the atoms linked to them, (17) When B is a 6- to 10-membered aryl or a 5- to 12-membered heteroaryl, D is hydrogen, halogen, cyano, hydroxy, C １ ~C ６ Alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, where the C １ ~C ６ Alkyl, 3-7 membered cycloalkyl, and 3-7 membered heterocycloalkyl groups may independently contain one, two, or three R groups. ｊ It is optionally substituted by, preferably D is hydrogen, C １ ~C ６ Conditions for being alkyl, (18) Each R ｉ These are independently hydrogen, halogen, hydroxyl, or C １ ~C ３ It is alkyl, or two R ｉ These form 3- to 7-membered cycloalkyl groups with the atoms linked to them. For example, R ｉ is hydrogen or C １ ~C ３ It is alkyl, Preferably, R ｉ C １ ~C ３ Conditions for being alkyl, (19) Each R ｊ These are hydrogen, halogen, and C, independently. １ ~C ３ Alkyl, 3-7 membered cycloalkyl, -OR １２－３ or -SR １２－４ And the above C １ ~C ３ Alkyl and 3- to 7-membered cycloalkyl groups independently have one, two, or three R groups. ｋ Replaced by choice, For example, each ｊ These are hydrogen, halogen, and C, independently. １ ~C ３ Alkyl, 3-7 membered cycloalkyl, -OR １２－３ or -SR １２－４ And, Also, for example, each R ｊ These are halogens and C １ ~C ３ Alkyl, OR １２－３ or SR １２－４ And, Furthermore, for example, each R ｊ C is independent １ ~C ３ Alkyl, OR １２－３ or SR １２－４ And the above C １ ~C ３ Alkyl groups may have one, two, or three independent R groups. ｋ They are optionally replaced by each R ｊ OR １２－３ or SR １２－４ And for example, OR １２－３ And, More preferably, each R ｊ These are, independently, halogen or C １ ~C ３ It is alkyl, Furthermore, X １ and X ３ ga-CR １ - and R １ C １ ~C ６ If it is alkyl, each R ｊ are independently -OR １２－３ or -SR １２－４ And, or, X １ or X ４ ga-CR １ - and R １ These independently comprise 3-7 member heterocycloalkyl groups or -NR groups. １－１ R １－２ If so, each R ｊ OR １２－３ or SR １２－４ The condition, (20) Each R ｋ The conditions for being a halogen independently are (21) Each R ｋ－１ The conditions for being a halogen independently are (22) In the 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, 5-6 member heteroaryl, and 5-12 member heteroaryl compounds, the heteroatoms are selected from one, two, or three of N, O, or S, and the number of heteroatoms is one, two, or three. (23) A 【Transformation 38】 X １ , X ２ and X ３ CR １ In that case, in the compound represented by formula I, E or F is 【Chemistry 39】 The condition, (24) R １２－１ , R １２－２ , R １２－３ and R １２－４ C is independent １ ~C ３ It is alkyl, and here, C １ ~C ３ Alkyl groups may have one, two, or three independent R groups. ｋ－１ It is optionally replaced by R １２－１ , R １２－２ , R １２－３ and R １２－４ C is independent １ ~C ３ Conditions for being alkyl, (25) In the 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, 5-6 member heteroaryl, and 5-12 member heteroaryl compounds, the heteroatoms are selected from one, two, or three of N, O, or S, and the number of heteroatoms is one, two, or three. For example, in the 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl compounds, the heteroatoms are N, O, or S, and the number of heteroatoms is one to five. Preferably, the 3- to 7-membered heterocycloalkyl group may also be a 3- to 6-membered heterocycloalkyl group, where the heteroatoms are, for example, one or two of N and O, and the number of heteroatoms is, for example, one or two. The aforementioned 4- to 6-membered heterocycloalkyl group may also be a 4-membered heterocycloalkyl group, where the heteroatoms are, for example, one or two of N and O, and the number of heteroatoms is, for example, one. The aforementioned 5- to 6-membered heteroaryl may also be a 6-membered heteroaryl, where the heteroatoms are, for example, one or two of N and O, and the number of heteroatoms is, for example, one. The aforementioned 5-12 membered heteroaryl may also be a 5-10 membered heterocycloalkyl, where the heteroatoms are, for example, one or two of N and O, and the number of heteroatoms is, for example, one. A compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that it satisfies any one of the following conditions.

6. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that the compound represented by formula I is the compound represented by formula I-1, the compound represented by formula I-2, the compound represented by formula I-3, the compound represented by formula I-4, or the compound represented by formula I-5. 【Chemistry 40】 (However, X ６ is N or CH, and X １ , R ｉ , X ２ , X ３ , X ４ , X ５ , Y, Z, m, n, E, R ｊ , R １ ,B,D,W,k,F,u,R ８ and R ９ (This is as described in claim 1 or 2.)

7. The compound represented by formula I-1 is the compound represented by formula I-1-1, the compound represented by formula I-1-2, the compound represented by formula I-1-3, or the compound represented by formula I-1-4. 【Chemistry 41】 、 Alternatively, the compound represented by formula I-5 is the compound represented by formula I-5-1, 【Chemistry 42】 Alternatively, the compound represented by formula I-4 is the compound represented by formula I-4-1, 【Chemistry 43】 、 However, R １ , R ｊ , R ８ , R ９ B, Z, n, X ６ , X ２ and X ４ The compound according to claim 6 or a pharmaceutically acceptable salt thereof, characterized in that it is as described in claim 6.

8. (1) X １ , X ２ , X ３ , X ４ and X ５ , independently -CR １ -, N, O, S, 【Chemistry 44】 or a chemical bond, and X １ , X ２ , X ３ , X ４ and X ５ The number of heteroatoms is 0, 1, 2, or 3. (2) X １ , X ２ , X ３ , X ４ and X ５ , independently -CR １ -, N, S, 【Chemistry 45】 or a chemical bond, and X １ , X ２ , X ３ , X ４ and X ５ The number of heteroatoms is one or two. （３） 【Chemistry 46】 In X １ , X ２ , X ３ and X ４ , independently -CR １ The condition is that it is - or N, and the number of heteroatoms is 0, 1, or 2. （４） 【Chemistry 47】 In this, Y and Z are independently carbonyl (CO) or -(CR ２ R ３ ) ｒ - and r is 1, R ２ and R ３ H, -(CH) are independent of each other. ２ )-,-(NHCH ２ )-,-(NHCH ２ CH ２ ) - or 【Chemistry 48】 The condition, （５） 【Chemistry 49】 In this case, Y and Z are independently - (CR ２ R ３ ) ｒ -, m is 2, n is 2, r is 1, R ２ and R ３ The conditions for H to be independent are （６） [Transformation 50] This is a benzo-5-membered heterocycloalkyl, where the heteroatom of the 5-membered heterocycloalkyl is N, and the number of heteroatoms is 1, for example, 【Chemistry 51】 And e is independently 0, 1, 2, or 3, and also, for example, 【Chemistry 52】 The condition, （７） 【Chemistry 53】 This is a benzo-7-membered heterocycloalkyl, where the heteroatom of the 7-membered heterocycloalkyl is N, and the number of heteroatoms is one or two, for example, 【Chemistry 54】 And e is independently 0, 1, 2, or 3, and also, for example, 【Transformation 55】 The condition, （８） 【Transformation 56】 This is a 6-membered heteroaryl condensed 5-membered heterocycloalkyl, where the heteroatom of the 6-membered heteroaryl is nitrogen, and the number of heteroatoms is one or two, preferably the heteroatom of the 5-membered heterocycloalkyl is nitrogen, and the number of heteroatoms is one, for example, 【Chemistry 57】 And e is independently 0, 1, or 2, and also, for example, 【Chemical Formula 58】 The condition, （９） 【Chemistry 59】 This is a 6-membered heteroaryl condensed 5-membered heterocycloalkyl, where the heteroatom of the 6-membered heteroaryl is N, and the number of heteroatoms is 1, for example, 【Transformation 60】 And e is independently 0, 1, 2, or 3, and also, for example, 【Chemistry 61】 The condition, （１０） 【Transformation 62】 This is a six-membered heteroaryl condensed six-membered heterocycloalkyl, where the heteroatom of the six-membered heteroaryl is nitrogen, and there is one heteroatom, preferably the heteroatom of the six-membered heterocycloalkyl is nitrogen, and there is one heteroatom, for example, 【Transformation 63】 And e is independently 0, 1, 2, or 3, and also, for example, 【Chemistry 64】 The condition, （１１） 【Transformation 65】 This is a 6-membered heteroaryl condensed 7-membered heterocycloalkyl, where the heteroatom of the 6-membered heteroaryl is nitrogen, and the number of heteroatoms is one or two, preferably the heteroatom of the 7-membered heterocycloalkyl is nitrogen, and the number of heteroatoms is one, for example, 【Chemical Formula 66】 And e is independently 0, 1, 2, or 3, and also, for example, 【Transformation 67】 The condition, （１２） 【Transformation 68】 This is a five-membered heteroaryl condensed five-membered heterocycloalkyl, where the heteroatoms of the five-membered heteroaryl are N and / or S, and the number of heteroatoms is one or two. For example, the heteroatoms of the five-membered heteroaryl are N or S, and the number of heteroatoms is one or two. Preferably, the heteroatom of the five-membered heterocycloalkyl is N, and the number of heteroatoms is one. For example, 【Transformation 69】 The condition, （１３） 【Transformation 70】 This is a 5-membered heteroaryl condensed 6-membered heterocycloalkyl, where the heteroatom of the 5-membered heteroaryl is nitrogen, and the number of heteroatoms is one or two. For example, the heteroatom of the 5-membered heteroaryl is nitrogen, and the number of heteroatoms is one. Preferably, the heteroatom of the 6-membered heterocycloalkyl is nitrogen, and the number of heteroatoms is one. For example, 【Chemistry 71】 And also, for example, 【Chemistry 72】 The condition, （１４） 【Transformation 73】 In X １ , X ２ , X ３ , X ４ and X ５ , independently -CR １ -, N, S, 【Chemistry 74】 or a chemical bond, and X １ , X ２ , X ３ , X ４ and X ５ The number of heteroatoms is 0, 1, or 2. （１５） 【Chemistry 75】 is C-(W) ｋ -And here, C is, 【Transformation 76】 C is a 5-membered heteroaryl, a 6-membered heteroaryl, or phenyl, preferably the heteroatom of the 5-membered heteroaryl is N, and the number of heteroatoms is one or two, or the heteroatom of the 6-membered heteroaryl is N, and the number of heteroatoms is one, for example, C is pyridyl, phenyl, or 【Chemical 77】 The condition, （１６） 【Transformation 78】 In this case, W is -O-, -CH ２ - or -NH- conditions, (17) In B, the 5-12 member heteroaryl is a 5-6 member heteroaryl, a benzo-5-6 member heteroaryl, a 5-7 member cycloalkyl condensed phenyl, a 5-7 member cycloalkyl condensed 5-6 member heteroaryl, a 5-6 member heteroaryl condensed 5-6 member heteroaryl, a 5-7 member heterocycloalkyl condensed 5-6 member heteroaryl, or a 5-7 member heterocycloalkyl condensed 5-6 member aryl, and more preferably a 5-6 member heteroaryl, a benzo-5-6 member heteroaryl, a 5-6 member heteroaryl condensed 5-6 member heteroaryl, a 5-7 member heterocycloalkyl condensed 5-6 member heteroaryl, or a 5-7 member heterocycloalkyl condensed phenyl. (18) In B, the heteroatom of the 4-6 member heterocycloalkyl is N, and the number of heteroatoms is 1, for example, 【Chemistry 79】 And e is independently 0, 1, 2, or 3, and also, for example, 【Chemistry 80】 The condition, (19) B is two R ｉ A 4-6 member heterocycloalkyl substituted with R on two identical atoms ｉ These atoms form a 3- to 7-membered cycloalkyl group with the atoms linked to them, and the 3- to 7-membered cycloalkyl group is preferably a 3- to 6-membered cycloalkyl group, for example, B is a 4-membered heterocycloalkyl group, and two R ｉ It forms a 3-4 membered cycloalkyl group, and for example, B is 【Chemistry 81】 The condition, (20) B is two R ｉ A 4-6 member heterocycloalkyl substituted at the ortho position, with two adjacent R ｉ These atoms form a 3- to 7-membered cycloalkyl group with the atoms linked to them, and the 3- to 7-membered cycloalkyl group is preferably a 3- to 6-membered cycloalkyl group, for example, B is a 5-membered heterocycloalkyl group, and two R ｉ It forms a three-membered cycloalkyl group, and for example, B is 【Chemistry 82】 The condition, (21) B is a five-membered heteroaryl compound, where the heteroatoms of the five-membered heteroaryl compound are N and / or S, and the number of heteroatoms is one or two, for example, the heteroatoms of the five-membered heteroaryl compound are N or S, and the number of heteroatoms is one or two, for example, 【Chemistry 83】 The condition, (22) B is a six-membered heteroaryl compound, where the heteroatom of the six-membered heteroaryl compound is N, and the number of heteroatoms is one or two, for example, 【Chemical 84】 The condition, (23) In B, the 6-10 member aryl is, for example, phenyl, (24) B is a benzo-5-membered heterocycloalkyl, where the heteroatom of the 5-membered heterocycloalkyl is N, and the number of heteroatoms is 1, for example, 【Chemical 85】 And e is independently 0, 1, 2, or 3, and also, for example, 【Chemical 86】 The condition, (25) B is a benzo-6-membered heteroaryl compound, where the heteroatom of the 6-membered heteroaryl compound is N, and the number of heteroatoms is one or two, for example, 【Chemistry 87】 The condition, (26) B is a benzo-6-membered heterocycloalkyl, where the heteroatoms of the 6-membered heterocycloalkyl are N and / or O, and the number of heteroatoms is one or two, for example, the heteroatoms of the 6-membered heterocycloalkyl are N or O, and the number of heteroatoms is one or two, for example, 【Chemical 88】 The condition, (27) B is a 6-membered heteroaryl condensed 5-membered heteroaryl, where the heteroatom of the 6-membered heteroaryl is N and there is one heteroatom, preferably the heteroatom of the 5-membered heteroaryl is N or S and there is one heteroatom, for example, 【Chemistry 89】 The condition, (28) B is a six-membered heteroaryl condensed six-membered heterocycloalkyl, where the heteroatom of the six-membered heteroaryl is N, and the number of heteroatoms is one, preferably the heteroatom of the six-membered heterocycloalkyl is O, and the number of heteroatoms is one, for example, [Chemical 90] The condition, (29) In D, the 5-12 member heteroaryl is a 5-6 member heteroaryl, a benzo-5-6 member heteroaryl, a 5-7 member cycloalkyl condensed phenyl, a 5-7 member cycloalkyl condensed 5-6 member heteroaryl, a 5-6 member heteroaryl condensed 5-6 member heteroaryl, a 5-7 member heterocycloalkyl condensed 5-6 member heteroaryl, or a 5-7 member heterocycloalkyl condensed 5-6 member aryl, preferably a 5-6 member heteroaryl, a benzo-5-6 member heteroaryl, a 5-7 member cycloalkyl condensed 5-6 member heteroaryl, a 5-6 member heteroaryl condensed 5-6 member heteroaryl, or a 5-7 member heterocycloalkyl condensed 5- The phenyl is a 6-membered heteroaryl or a 5-7 membered heterocycloalkyl condensed phenyl, more preferably a 5-6 membered heteroaryl, a benzo-5-6 membered heteroaryl, a 5-7 membered cycloalkyl condensed 5-6 membered heteroaryl, a 5-6 membered heteroaryl condensed 5-6 membered heteroaryl, a 5-7 membered heterocycloalkyl condensed 5-6 membered heteroaryl, or a 5-7 membered heterocycloalkyl condensed phenyl, where, in the 5-6 membered heteroaryl and 5-7 membered heterocycloalkyl, the heteroatoms are preferably selected from one, two, or three of N, O, and S, and the number of heteroatoms is preferably one, two, or three. (30) In D, the 5-6 member heteroaryl is a 5-member heteroaryl or a 6-member heteroaryl, (31) D is hydrogen, methyl, ethyl, isopropyl, cyclopropyl, or trifluoromethyl, (32) D is a six-membered heteroaryl compound, where the heteroatom of the six-membered heteroaryl compound is N, and the number of heteroatoms is one or two, for example, 【Chemistry 91】 And e is independently 0, 1, 2, or 3, and also, for example, 【Chemistry 92】 The condition, (33) D is a five-membered heteroaryl compound, where the heteroatoms of the five-membered heteroaryl compound are N or S, and the number of heteroatoms is one, two, or three, for example, 【Chemistry 93】 The condition, (34) D is a 6-membered heteroaryl condensed 5-membered heterocycloalkyl, where the heteroatom of the 6-membered heteroaryl is N and there is one heteroatom, preferably the heteroatom of the 5-membered heterocycloalkyl is N or O and there is one heteroatom, for example, 【Chemical 94】 And e is independently 0, 1, 2, or 3, and also, for example, 【Chemical 95】 The condition, (35) D is a 6-membered heteroaryl condensed 5-membered cycloalkyl, where the heteroatom of the 6-membered heteroaryl is N, and the number of heteroatoms is 1, for example, 【Chemistry 96】 And e is independently 0, 1, 2, or 3, and also, for example, 【Chemistry 97】 The condition, A compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that it satisfies any one of the following conditions.

9. （１） 【Chem.98】 This is a 6-membered heteroaryl condensed 5-membered heterocycloalkyl, where the heteroatom of the 6-membered heteroaryl is N and there are 2 heteroatoms, and the heteroatom of the 5-membered heterocycloalkyl may also be N and there is 1 heteroatom, for example, 【Chem.99】 And e is independently 0, 1, or 2, (2) B is two R ｉ A 4-6 member heterocycloalkyl substituted with R on two identical atoms ｉ These atoms form a 3- to 7-membered cycloalkyl group with the atoms linked to them, and the 3- to 7-membered cycloalkyl group is preferably a 3- to 6-membered cycloalkyl group, for example, B is a 4-membered heterocycloalkyl group or a 5-membered heterocycloalkyl group, and the two R ｉ It forms a 3-4 membered cycloalkyl group, and for example, B is 【Chemistry 100】 The condition, (3) D is a five-membered heteroaryl compound, where the heteroatoms of the five-membered heteroaryl compound are selected from one or more of N, S, and O, and the number of heteroatoms is one, two, or three, for example, 【Chemistry 101】 The condition, (4) D is a benzo-5-membered heteroaryl compound, where the heteroatoms of the 5-membered heteroaryl compound are N and / or S, and the number of heteroatoms is 2, for example, 【Chemical Engineering 102】 And e is independently 0, 1, 2, or 3, and also, for example, 【Chemistry 103】 The condition, (5) D is a 5-6 member heteroaryl condensate, where the heteroatoms of the 5-6 member heteroaryl are N and / or S, and the number of heteroatoms is one, two, or three, for example, 【Chemical 104】 And e is independently 0, 1, 2, or 3, (6) D is a 5-6 member heteroaryl condensed 5-6 member heterocycloalkyl, where the heteroatom of the 5-6 member heteroaryl is N, and the number of heteroatoms is 1, 2, or 3, preferably the heteroatom of the 5-6 member heterocycloalkyl is O, and the number of heteroatoms is 1, 2, or 3, for example, 【Chemistry 105】 And e is independently 0, 1, 2, or 3, (7) D is a benzo-5-6 member heterocycloalkyl, where the heteroatoms of the 5-6 member heterocycloalkyl are one or more of O, N, and O, and the heteroatoms are one, two, or three, for example, 【Chemistry 106】 And e is independently 0, 1, 2, or 3, (8) D is a benzo-5-6 member heteroaryl compound, where the heteroatom of the 5-6 member heteroaryl compound is N, and the number of heteroatoms is one, two, or three, for example, 【Chemistry 107】 And e is independently 0, 1, 2, or 3, A compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that it satisfies any one of the following conditions.

10. Scheme 1: 【Chemistry 108】 teeth, 【Chemistry 109】 And, m is a natural number between 1 and 3. n is a natural number between 1 and 3. k is a natural number between 1 and 3. X １ , X ２ , X ３ , X ４ and X ５ , independently -CR １ -, N, O, S, 【Chemical 110】 or a chemical bond, and X １ , X ２ , X ３ , X ４ and X ５ The number of heteroatoms is 0, 1, 2, or 3. R Ｎ－１ is hydrogen, or C １ ~C ６ It is alkyl, Y and Z are independently carbonyl (CO) or -(CR ２ R ３ ) ｒ - and r is a natural number between 1 and 2. Each W is independently -O-, -(CR ４ R ５ ) -, -NR ６ - or a chemical bond, Each R １ These are hydrogen, halogen, and C, independently. １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl or -NR １－１ R １－２ And here, C １ ~C ６ Alkyl and C １ ~C ６ Alkoxy can independently have one, two, three, or four R ａ Replaced by choice, Each R ａ These are independently hydroxy, C １ ~C ３ Alkoxy or NR １－４ R １－５ And, R １－１ and R １－２ These are independently hydrogen or C １ ~C ６ It is alkyl, and here, C １ ~C ６ Alkyl groups may independently have one, two, three, or four R groups. ｂ It is optionally replaced by R １－１ and R １－２ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. Each R ｂ These are independently hydroxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, and C １ ~C ３ Alkyl, C １ ~C ３ Alkoxy or NR １－１－１ R １－２－１ Here, the 3-7 member cycloalkyl, 3-7 member heterocycloalkyl and C １ ~C ３ Alkyl groups may independently have one, two, three, or four R groups. ｂ－１ Replaced by choice, Each R ｂ－１ It is independently hydroxyl, R １－４ and R １－５ These are independently hydrogen or C １ ~C ３ It is alkyl, and here, C １ ~C ３ Alkyl groups can optionally consist of one, two, three, or four R groups. １－４－１ It is optionally replaced by R １－４ and R １－５ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. Each R １－４－１ It is independently a halogen, R １－１－１ and R １－２－１ These are independently hydrogen or C １ ~C ３ It is alkyl, R ２ and R ３ It is independently hydrogen or NR ２－１ R ２－２ And, R ２－１ and R ２－２ These are independently hydrogen or C １ ~C ６ It is alkyl, R ４ , R ５ and R ６ It is independently hydrogen, L is 【Chemistry 111】 And, t is a natural number between 0 and 2. u is a natural number between 0 and 2. E is a carbonyl, -NHCO-, or chemical bond. F is -O-, -NH-, or a chemical bond. R ８ and R ９ These are independently hydrogen or C １ ~C ６ It is alkyl, or R ８ and R ９ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. B is a 4-6 member heterocycloalkyl, a 6-10 member aryl, or a 5-12 member heteroaryl, where the 5-12 member heteroaryl, 6-10 member aryl, and 4-6 member heterocycloalkyl are independently one, two, or three R ｉ Replaced by choice, Each R ｉ These are independently hydrogen, halogen, hydroxyl, or C １ ~C ３ It is alkyl, or two R ｉ These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, or two adjacent R ｉ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. D is hydrogen, 3-7 member cycloalkyl, C １ ~C ６ It is an alkyl or a 5-12 member heteroaryl, where the C １ ~C ６ Alkyl and 5- to 12-membered heteroaryl groups independently have one, two, or three R groups. ｊ Replaced by choice, Each R ｊ These are halogens and C １ ~C ３ Alkyl, -OR １２－３ or -SR １２－４ And the above C １ ~C ３ Alkyl groups may have one, two, or three independent R groups. ｋ This is optionally replaced by each R ｋ It is independently a halogen, R １２－３ and R １２－４ C is independent １ ~C ３ Alkyl, and the C １ ~C ３ Alkyl groups may have one, two, or three independent R groups. ｋ This is optionally replaced by each R ｋ It is independently a halogen, In the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl compounds, the heteroatoms are N, O, or S, and the number of heteroatoms is 1 to 3; or, in the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl compounds, the heteroatoms are selected from one or more of N, O, and S, and the number of heteroatoms is 1 to 3. Scheme 2: 【Chemistry 112】 teeth, 【Chemistry 113】 And, m is a natural number between 1 and 3. n is a natural number between 1 and 3. X １ , X ２ , X ３ and X ４ , independently -CR １ -, N, S, 【Chemistry 114】 or a chemical bond, and X １ , X ２ , X ３ , X ４ and X ５ The number of heteroatoms is one or two. R Ｎ－１ C １ ~C ６ It is alkyl, Y and Z are independently carbonyl (CO) or -(CR ２ R ３ ) ｒ - and r is a natural number between 1 and 2. Each R １ These are hydrogen, halogen, and C, independently. １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl or -NR １－１ R １－２ And here, C １ ~C ６ Alkyl and C １ ~C ６ Alkoxy can independently have one, two, three, or four R ａ Replaced by choice, Each R ａ These are independently hydroxy, C １ ~C ３ Alkoxy or NR １－４ R １－５ And, R １－１ and R １－２ These are independently hydrogen or C １ ~C ６ It is alkyl, and here, C １ ~C ６ Alkyl groups may independently have one, two, three, or four R groups. ｂ It is optionally replaced by R １－１ and R １－２ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. Each R ｂ These are independently hydroxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, and C １ ~C ３ Alkyl, C １ ~C ３ Alkoxy or NR １－１－１ R １－２－１ Here, the 3-7 member cycloalkyl, 3-7 member heterocycloalkyl and C １ ~C ３ Alkyl groups may independently have one, two, three, or four R groups. ｂ－１ Replaced by choice, Each R ｂ－１ It is independently hydroxyl, R １－４ and R １－５ These are independently hydrogen or C １ ~C ３ It is alkyl, and here, C １ ~C ３ Alkyl groups may independently have one, two, three, or four R groups. １－４－１ It is optionally replaced by R １－４ and R １－５ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. R １－１－１ and R １－２－１ These are independently hydrogen or C １ ~C ３ It is alkyl, Each R １－４－１ It is independently a halogen, R ２ and R ３ It is independently hydrogen, L is 【Chemical 115】 And, t is a natural number between 0 and 2. u is a natural number between 0 and 2. E is a carbonyl or chemical bond, F is -O-, -NH-, or a chemical bond. R ８ and R ９ C is independent １ ~C ６ It is alkyl, or R ８ and R ９ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. B is a 4-6 member heterocycloalkyl or a 5-12 member heteroaryl, where the 5-12 member heteroaryl and 4-6 member heterocycloalkyl are independently one, two or three R ｉ Replaced by choice, Each R ｉ These are independently hydrogen, halogen, hydroxyl, or C １ ~C ３ It is alkyl, or two R ｉ These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, or two adjacent R ｉ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. D is hydrogen, 3-7 member cycloalkyl, C １ ~C ６ It is an alkyl or a 5-6 member heteroaryl, where the C １ ~C ６ Alkyl and 5-6 member heteroaryl groups independently have one, two, or three R groups. ｊ Replaced by choice, Each R ｊ These are, independently, halogen or C １ ~C ３ Alkyl, and the C １ ~C ３ Alkyl groups may have one, two, or three independent R groups. ｋ This is optionally replaced by each R ｋ It is independently a halogen, In the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, 5-6 member heteroaryl, and 5-12 member heteroaryl compounds, the heteroatoms are N, O, or S, and the number of heteroatoms is 1 to 3; or, in the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, 5-6 member heteroaryl, and 5-12 member heteroaryl compounds, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 3. Scheme 3: 【Chemistry 116】 teeth, 【Chemistry 117】 And, m is a natural number between 1 and 2. n is a natural number between 1 and 2. k is a natural number between 1 and 3. X １ , X ２ , X ３ , X ４ and X ５ , independently -CR １ -, N, O, S, 【Chemistry 118】 or a chemical bond, and X １ , X ２ , X ３ , X ４ and X ５ The number of heteroatoms is 0, 1, 2, or 3. R Ｎ－１ C １ ~C ６ It is alkyl, Each W is independently - (CR ４ R ５ )-, -O-, -NR ６ - or chemical bond, where Y and Z are independently carbonyl (CO) or -(CR ２ R ３ ) ｒ - and r is a natural number between 1 and 2. Each R １ These are hydrogen, halogen, and C, independently. １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl or -NR １－１ R １－２ And here, C １ ~C ６ Alkyl and C １ ~C ６ Alkoxy can independently have one, two, three, or four R ａ Replaced by choice, Each R ａ These are independently hydroxy, C １ ~C ３ Alkoxy or NR １－４ R １－５ And, R １－１ and R １－２ These are independently hydrogen or C １ ~C ６ It is alkyl, and here, C １ ~C ６ Alkyl groups may independently have one, two, three, or four R groups. ｂ It is optionally replaced by R １－１ and R １－２ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. Each R ｂ These are independently hydroxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, and C １ ~C ３ Alkyl, C １ ~C ３ Alkoxy or NR １－１－１ R １－２－１ Here, the 3-7 member cycloalkyl, 3-7 member heterocycloalkyl and C １ ~C ３ Alkyl groups may independently have one, two, three, or four R groups. ｂ－１ Replaced by choice, Each R ｂ－１ It is independently hydroxyl, R １－４ and R １－５ These are independently hydrogen or C １ ~C ３ It is alkyl, and here, C １ ~C ３ Alkyl groups may independently have one, two, three, or four R groups. １－４－１ It is optionally replaced by R １－４ and R １－５ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. R １－１－１ and R １－２－１ These are independently hydrogen or C １ ~C ３ It is alkyl, Each R １－４－１ It is independently a halogen, R ２ and R ３ It is independently hydrogen or NR ２－１ R ２－２ And, R ２－１ and R ２－２ These are independently hydrogen or C １ ~C ６ It is alkyl, R ４ , R ５ and R ６ is independently hydrogen, and L is, 【Chemical 119】 And, t is a natural number between 0 and 2. u is a natural number between 0 and 2. E is a carbonyl, -NHCO-, or chemical bond. F is -O-, -NH-, or a chemical bond. R ８ and R ９ These are independently hydrogen or C １ ~C ６ It is alkyl, or R ８ and R ９ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. B is a 4-6 member heterocycloalkyl, a 6-10 member aryl, or a 5-12 member heteroaryl, where the 5-12 member heteroaryl, 6-10 member aryl, and 4-6 member heterocycloalkyl are independently one, two, or three R ｉ Replaced by choice, Each R ｉ These are independently hydrogen, hydroxyl, halogen, or C １ ~C ３ It is alkyl, or two R ｉ These atoms form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl with the atoms linked to them, or two adjacent R ｉ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. D is hydrogen, C １ ~C ６ It is an alkyl or a 5-12 member heteroaryl, where the C １ ~C ６ Alkyl and 5- to 12-membered heteroaryl groups independently have one, two, or three R groups. ｊ Replaced by choice, Each R ｊ These are halogens and C １ ~C ３ Alkyl, OR １２－３ or SR １２－４ And the above C １ ~C ３ Alkyl groups may have one, two, or three independent R groups. ｋ This is optionally replaced by each R ｋ It is independently a halogen, R １２－３ and R １２－４ C is independent １ ~C ３ It is alkyl, and here, C １ ~C ３ Alkyl groups may have one, two, or three independent R groups. ｋ－１ This is optionally replaced by each R ｋ－１ Independently, each is a halogen, and in the 3-7 membered heterocycloalkyl, 4-6 membered heterocycloalkyl, and 5-12 membered heteroaryl compounds, the heteroatoms are N, O, or S, and the number of heteroatoms is 1 to 3, or in the 3-7 membered heterocycloalkyl, 4-6 membered heterocycloalkyl, and 5-12 membered heteroaryl compounds, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 3. Scheme 4: 【Chemical 120】 teeth, 【Chemistry 121】 And, m is a natural number between 0 and 3. n is a natural number between 0 and 3, and m and n are not both 0 at the same time. k is a natural number between 0 and 3. X １ , X ２ , X ３ , X ４ and X ５ , independently -CR １ -, N, S, 【Chemistry 122】 or chemical bond, R Ｎ－１ is hydrogen, C １ ~C ６ Alkyl or 3-7 membered cycloalkyl, Y and Z are independently carbonyl (CO) or -(CR ２ R ３ ) ｒ - and r is a natural number from 0 to 5. Each W is independently -O-, -(CR ４ R ５ ) -, -NR ６ - or a chemical bond, Each R １ These are hydrogen, halogen, and C, independently. １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, C １ ~C ６ Alkylthio, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl or -NR １－１ R １－２ And here, C １ ~C ６ Alkylthio, C １ ~C ６ Alkyl and C １ ~C ６ Alkoxy can independently have one, two, three, or four R ａ Replaced by choice, Each R ａ These are independently halogen, hydroxyl, and C １ ~C ６ Alkoxy or -NR １－４ R １－５ And, R １－１ and R １－２ These are independently hydrogen or C １ ~C ６ It is alkyl, and here, C １ ~C ６ Alkyl groups may independently have one, two, three, or four R groups. ｂ It is optionally replaced by R １－１ and R １－２ These atoms form a 3- to 7-membered heterocycloalkyl group with the atoms linked to them, where the 3- to 7-membered heterocycloalkyl group has one, two, three, or four R atoms. ｂ－２ Replaced by choice, Each R ｂ These are independently hydroxy, 3- to 7-membered cycloalkyl, or C １ ~C ３ It is alkyl, Each R ｂ－２ These are, independently, halogen or C １ ~C ６ It is alkyl, R １－４ and R １－５ These are independently hydrogen or C １ ~C ３ It is alkyl, and here, C １ ~C ３ Alkyl groups may independently have one, two, three, or four R groups. １－４－１ It is optionally replaced by R １－４ and R １－５ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. Each R １－４－１ It is independently a halogen, R ２ and R ３ It is independently hydrogen or NR ２－１ R ２－２ And, R ２－１ and R ２－２ These are independently hydrogen or C １ ~C ６ It is alkyl, R ４ , R ５ and R ６ It is independently hydrogen or NR ４－１ R ４－２ And, R ４－１ and R ４－２ It is independently hydrogen, L is [Chemical 123] And, t is a natural number between 0 and 3. u is a natural number between 0 and 3. E is carbonyl, 【Chemistry 124】 , -NHCO- or a chemical bond, F is carbonyl, 【Chemistry 125】 , -O-, -NH- or chemical bond, R ８ and R ９ These are independently hydrogen or C １ ~C ６ It is alkyl, or R ８ and R ９ These form 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl groups with atoms linked to them. B is a 4-6 member heterocycloalkyl, a 6-10 member aryl, or a 5-12 member heteroaryl, where the 4-6 member heterocycloalkyl, 6-10 member aryl, and 5-12 member heteroaryl are independently one, two, or three R ｉ Replaced by choice, Each R ｉ These are independently hydrogen, halogen, hydroxyl, or C １ ~C ３ Alkyl, or R on two identical atoms ｉ These atoms form a 3- to 7-membered cycloalkyl group with the atoms linked to them, or two adjacent R ｉ These form 3- to 7-membered cycloalkyl groups with the atoms linked to them. D is hydrogen, C １ ~C ６ It is an alkyl or a 5-12 member heteroaryl, where the C １ ~C ６ Alkyl and 5- to 12-membered heteroaryl groups independently have one, two, or three R groups. ｊ Replaced by choice, Each R ｊ These are hydrogen, halogen, and C, independently. １ ~C ３ Alkyl, 3-7 membered cycloalkyl, -OR １２－３ or -SR １２－４ And the above C １ ~C ３ Alkyl and 3- to 7-membered cycloalkyl groups independently have one, two, or three R groups. ｋ Replaced by choice, R １２－３ and R １２－４ C is independent １ ~C ３ It is alkyl, and here, C １ ~C ３ Alkyl groups may have one, two, or three independent R groups. ｋ－１ Replaced by choice, Each R ｋ It is independently a halogen, Each R ｋ－１ It is independently a halogen, In the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 3. Scheme 5: 【Chemistry 126】 teeth, 【Chemistry 127】 And, m is a natural number between 0 and 3. n is a natural number between 0 and 3, and m and n are not both 0 at the same time. k is a natural number between 0 and 3. X １ , X ２ , X ３ , X ４ and X ５ , independently -CR １ -, N, S, 【Chemistry 128】 or chemical bond, R Ｎ－１ C １ ~C ６ It is alkyl, Y and Z are independently carbonyl (CO) or -(CR ２ R ３ ) ｒ - and r is a natural number from 0 to 5. Each W is independently - (CR ４ R ５ ) -, -NR ６ - or a chemical bond, Each R １ These are hydrogen, halogen, and C, independently. １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, C １ ~C ６ Alkylthio, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl or -NR １－１ R １－２ And here, C １ ~C ６ Alkylthio, C １ ~C ６ Alkyl and C １ ~C ６ Alkoxy can independently have one, two, three, or four R ａ Replaced by choice, Each R ａ These are independently hydroxy, C １ ~C ６ Alkoxy or -NR １－４ R １－５ And, R １－１ and R １－２ These are independently hydrogen or C １ ~C ６ It is alkyl, and here, C １ ~C ６ Alkyl groups may independently have one, two, three, or four R groups. ｂ It is optionally replaced by R １－１ and R １－２ These atoms form a 3- to 7-membered heterocycloalkyl group with the atoms linked to them, where the 3- to 7-membered heterocycloalkyl group has one, two, three, or four R atoms. ｂ－２ Replaced by choice, Each R ｂ These are independently 3- to 7-membered cycloalkyl groups. Each R ｂ－２ These are, independently, halogen or C １ ~C ６ It is alkyl, R １－４ and R １－５ C is independent １ ~C ３ It is alkyl, R ２ and R ３ It is independently hydrogen or NR ２－１ R ２－２ And, R ２－１ and R ２－２ It is independently hydrogen, R ４ , R ５ and R ６ It is independently hydrogen, L is 【Chemistry 129】 And, t is a natural number between 0 and 3. u is a natural number between 0 and 3. E is carbonyl, 【Chemistry 130】 , -NHCO- or a chemical bond, F is a chemical bond, R ８ and R ９ These are independently hydrogen or C １ ~C ６ It is alkyl, or R ８ and R ９ These form 3- to 7-membered cycloalkyl groups with the atoms linked to them. B is a 4-6 member heterocycloalkyl, a 6-10 member aryl, or a 5-12 member heteroaryl, where the 4-6 member heterocycloalkyl, 6-10 member aryl, and 5-12 member heteroaryl are independently one, two, or three R ｉ Replaced by choice, Each R ｉ These are independently hydrogen, halogen, hydroxyl, or C １ ~C ３ Alkyl, or R on two identical atoms ｉ These form 3- to 7-membered cycloalkyl groups with the atoms linked to them. D is hydrogen, C １ ~C ６ It is an alkyl or a 5-12 member heteroaryl, where the C １ ~C ６ Alkyl and 5- to 12-membered heteroaryl groups independently have one, two, or three R groups. ｊ Replaced by choice, Each R ｊ These are hydrogen, halogen, and C, independently. １ ~C ３ Alkyl, 3-7 membered cycloalkyl, -OR １２－３ or -SR １２－４ And the above C １ ~C ３ Alkyl and 3- to 7-membered cycloalkyl groups independently have one, two, or three R groups. ｋ Replaced by choice, R １２－３ and R １２－４ C is independent １ ~C ３ It is alkyl, and here, C １ ~C ３ Alkyl groups may have one, two, or three independent R groups. ｋ－１ Replaced by choice, Each R ｋ It is independently a halogen, Each R ｋ－１ It is independently a halogen, In the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 3. Scheme 6: Here, 【Chemistry 131】 teeth, 【Chemistry 132】 And, m is 1, n is 1, X １ , X ２ , X ３ and X ４ , independently -CR １ - or N, and X １ , X ２ , X ３ and X ４ The number of heteroatoms is two. Y and Z are independent of (CR ２ R ３ ) ｒ - and r is 1, Each R １ C is independent １ ~C ６ Alkyl or C １ ~C ６ It is an alkoxy, R ２ and R ３ It is independently hydrogen, L is 【Chemistry 133】 And, t is 0, u is 1, E is a carbonyl group, F is a chemical bond, B is a 4-6 member heterocycloalkyl group, where the 4-6 member heterocycloalkyl group independently has one, two, or three R groups. ｉ Replaced by choice, Each R ｉ It is independently hydrogen, D is a 5- to 12-membered heteroaryl, where the 5- to 12-membered heteroaryl is independently one, two, or three R ｊ Replaced by choice, Each R ｊ are independently -OR １２－３ And, R １２－３ C １ ~C ３ Alkyl, and the C １ ~C ３ Alkyl groups may have one, two, or three independent R groups. ｋ This is optionally replaced by each R ｋ It is independently a halogen, In the aforementioned 4-6 member heterocycloalkyl and 5-12 member heteroaryl compounds, the heteroatoms are N, O, or S, and the number of heteroatoms is 1 to 3; or, in the aforementioned 4-6 member heterocycloalkyl and 5-12 member heteroaryl compounds, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 3. A 【Chemistry 134】 If X １ , X ２ and X ４ The number of heteroatoms is one or two. A 【Chemistry 135】 And if L is a carbonyl group, then u is a natural number from 1 to 3, B is a 4-6 member heterocycloalkyl group, and the 4-6 member heterocycloalkyl group independently has one, two or three R groups. ｉ Replaced by choice, Scheme 7: Here, 【Transformation 136】 teeth, 【Chemistry 137】 And, m is 1, n is 1, X ２ and X ３ N is, X １ and X ４ , independently -CR １ - and Y and Z are independent of (CR ２ R ３ ) ｒ - and r is 1, Each R １ These are hydrogen, halogen, and C, independently. １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl or -NR １－１ R １－２ And here, C １ ~C ６ Alkyl and C １ ~C ６ Alkoxy can independently have one, two, three, or four R ａ Replaced by choice, R １－１ and R １－２ These are independently hydrogen or C １ ~C ６ It is alkyl, or R １－１ and R １－２ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. Each R ａ These are independently hydroxy, C １ ~C ６ Alkoxy or NR １－４ R １－５ And, R １－４ and R １－５ These are independently hydrogen or C １ ~C ３ It is alkyl, R ２ and R ３ It is independently hydrogen, L is 【Chemistry 138】 And, t is 0, u is 1, E is a carbonyl group, F is a chemical bond, B is a 4-6 member heterocycloalkyl group, where the 4-6 member heterocycloalkyl group independently has one, two, or three R groups. ｉ Replaced by choice, Each R ｉ These are independently hydrogen, halogen, hydroxyl, or C １ ~C ３ It is alkyl, D is a 5- to 12-membered heteroaryl, where the 5- to 12-membered heteroaryl is independently one, two, or three R ｊ It is optionally substituted by, preferably, D is a 5-6 member heteroaryl, where the 5-6 member heteroaryl is independently one, two or three R ｊ The heteroatoms are optionally substituted by the above, and in the 5-6 member heteroaryl, the heteroatoms are selected from one, two, or three of N, S, and O, and the number of heteroatoms is one, two, or three. Each R ｊ These are independently H, halogen, and C. １ ~C ３ Alkyl, OR １２－３ or SR １２－４ And here, C １ ~C ３ Alkyl groups may have one, two, or three independent R groups. ｋ Replaced by choice, R １２－３ and R １２－４ C is independent １ ~C ３ Alkyl, and the C １ ~C ３ Alkyl groups may have one, two, or three independent R groups. ｋ－１ Replaced by choice, Each R ｋ These are, independently, halogen or C １ ~C ３ It is alkyl, Each R ｋ－１ These are, independently, halogen or C １ ~C ３ It is alkyl, In the aforementioned 3-7 member heterocycloalkyl, 4-6 member heterocycloalkyl, and 5-12 member heteroaryl, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 3. Scheme 8: Here, 【Chemistry 139】 teeth, [Chemistry 140] And, m is 1, n is 1, X １ and X ３ N is, X ２ and X ４ , independently -CR １ - and Y and Z are independent of (CR ２ R ３ ) ｒ - and r is 1, Each R １ These are independently hydrogen, halogen, cyano, hydroxyl, and C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, C １ ~C ６ Alkylthio, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl or -NR １－１ R １－２ And here, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy and C １ ~C ６ Alkylthio can independently have one, two, three, or four R groups. ａ Replaced by choice, R １－１ and １－２ These are independently hydrogen or C １ ~C ６ It is alkyl, or R １－１ and R １－２ These form 3- to 7-membered heterocycloalkyl groups with the atoms linked to them. Each R ａ These are independently hydroxy, C １ ~C ６ Alkoxy or NR １－４ R １－５ And, R １－４ and R １－５ These are independently hydrogen or C １ ~C ３ It is alkyl, R ２ and R ３ It is independently hydrogen, L is 【Chemistry 141】 And, t is 0, u is 1, E is a carbonyl group, F is a chemical bond, B is a 4-6 member heterocycloalkyl group, where the 4-6 member heterocycloalkyl group independently has one, two, or three R groups. ｉ Replaced by choice, Each R ｉ These are independently hydrogen, halogen, hydroxyl, or C １ ~C ３ It is alkyl, or two R ｉ These form 3- to 7-membered cycloalkyl groups with the atoms linked to them. D is a 5- to 12-membered heteroaryl, where the 5- to 12-membered heteroaryl is independently one, two, or three R ｊ It is optionally substituted by, preferably, D is a 5-6 member heteroaryl, where the 5-6 member heteroaryl is independently one, two or three R ｊ The heteroatoms are optionally substituted by the above, and in the 5-6 member heteroaryl, the heteroatoms are selected from one, two, or three of N, S, and O, and the number of heteroatoms is one, two, or three. Each R ｊ These are independently hydrogen, halogen, cyano, hydroxyl, and C １ ~C ３ Alkyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, -NR １２－１ R １２－２ , -OR １２－３ or -SR １２－４ And here, C １ ~C ３ Alkyl, 3- to 7-membered cycloalkyl, and 3- to 7-membered heterocycloalkyl groups may independently have one, two, or three R groups. ｋ Replaced by choice, R １２－１ , R １２－２ , R １２－４ and R １２－３ C is independent １ ~C ３ Alkyl, and the C １ ~C ３ Alkyl groups may have one, two, or three independent R groups. ｋ－１ Replaced by choice, Each R ｋ These are, independently, halogen or C １ ~C ３ It is alkyl, Each R ｋ－１ These are, independently, halogen or C １ ~C ３ It is alkyl, In the aforementioned 3-7 membered heterocycloalkyl, 4-6 membered heterocycloalkyl, and 5-12 membered heteroaryl, the heteroatoms are one or more of N, O, and S, and the number of heteroatoms is 1 to 3. A compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that it satisfies any one of the following conditions.

11. （１） 【Chemistry 142】 teeth, 【Chemistry 143】 The condition, (2) The condition that m is 1, (3) n is 1 under the following conditions: (4) X １ , X ２ , X ３ and X ４ , independently -CR １ - or N, and X １ , X ２ , X ３ and X ４ The number of heteroatoms is two, (5) Y and Z are independent of (CR ２ R ３ ) ｒ - and r is 1, (6) Each R １ C is independent １ ~C ６ Alkyl or C １ ~C ６ Conditions for being alkoxy, (7) The condition for t to be 0 is (8) u is 1 under the following conditions (9) E is a carbonyl compound, (10) F is a chemical bond, (11) B is a 4-6 member heterocycloalkyl, where the 4-6 member heterocycloalkyl is independently one, two or three R ｉ Conditions that are optionally replaced by, (12) Each R ｉ The condition is that it is hydrogen independently. (13) D is a 5- to 12-membered heteroaryl, where the 5- to 12-membered heteroaryl is independently one, two or three R ｊ It is optionally substituted by, preferably, D is a 5-6 member heteroaryl, where the 5-6 member heteroaryl is independently one, two or three R ｊ The following conditions apply: The 5-6 member heteroaryl is optionally substituted, and in the 5-6 member heteroaryl, the heteroatoms are selected from one, two, or three of N, S, and O, and the number of heteroatoms is one, two, or three. (14) Each R ｊ Independently, Hello OR １２－３ The condition, (15) R １２－３ C １ ~C ３ Alkyl, and the C １ ~C ３ Alkyl groups may have one, two, or three independent R groups. ｋ This is optionally replaced by each R ｋ The conditions for being a halogen independently are A compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that it satisfies any one of the following conditions.

12. (1) Each R １ These are independently hydrogen, methyl, 【Chemistry 144】 ethyl, chlorine, 【Chemistry 145】 methoxy, 【Chemistry 146】 isopropyl, 【Chemistry 147】 , amino(-NH ２ ), 【Chemistry 148】 , trifluoromethyl, 【Chemistry 149】 or methylthio, for example, each R １ These are independently hydrogen, methyl, methoxy, [Chemical 150] ethyl, chlorine, 【Chemistry 151】 methoxy, 【Chemistry 152】 isopropyl, 【Chemistry 153】 ,amino, 【Chemistry 154】 Preferably, each R １ These are independently methyl, methoxy, 【Chemistry 155】 The condition, （２） 【Chemistry 156】 teeth, 【Chemistry 157】 【change】 【change】 【change】 For example, 【Chemistry 158】 teeth, 【Chemistry 159】 【change】 【change】 Preferably, [Chemical 160] teeth, 【Chemistry 161】 The condition, (3) L is -(CH ２ )-,-(CH ２ ) ２ - 【Chemistry 162】 Preferably, L is 【Chemistry 163】 And here, 【Chemistry 164】 " indicates that it is connected to A, and more preferably L is -(CH ２ )-,-(CH ２ ) ２ - 【Chemistry 165】 Furthermore, L is, 【Chemistry 166】 And here, 【Chemistry 167】 " indicates that it is connected to A, and more preferably, L is 【Chemical 168】 The condition, (4) B is, 【Chemistry 169】 For example, B is 【Chemistry 170】 Preferably, B is 【Chemistry 171】 The condition, (5) D is hydrogen, methyl, 【Chemistry 172】 ethyl, isopropyl, cyclopropyl, trifluoromethyl or 【Chemistry 173】 For example, D is hydrogen, methyl, 【Chemistry 174】 ethyl, isopropyl, cyclopropyl, trifluoromethyl or 【Chemistry 175】 Preferably, D is 【Chemistry 176】 The condition, A compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that it satisfies any one of the following conditions.

13. A compound represented by formula I according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized by being one of the following compounds. 【Chemistry 177】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】

14. Choose one of the following schemes: Scheme (a): In an organic solvent, in the presence of a catalyst, the compound represented by formula II and the compound represented by formula III are subjected to the condensation reaction shown below to obtain the compound represented by formula I. 【Chemistry 178】 Scheme (b): In an organic solvent, in the presence of a catalyst, the compound represented by formula IV and the compound represented by formula V are subjected to the condensation reaction shown below to obtain the compound represented by formula I. 【Chemistry 179】 Scheme (C): In an organic solvent, in the presence of a catalyst, the compound represented by formula VI and the compound represented by formula VII are subjected to the cyclization reaction shown below to obtain the compound represented by formula I. 【Transformation 180】 Scheme (D): In an organic solvent, in the presence of a catalyst, the compound represented by formula VIII and the compound represented by formula VIII are subjected to the cyclization reaction shown below to obtain the compound represented by formula I. 【Chemistry 181】 However, Z is a halogen, TsO-, hydroxy, methoxy, ethoxy, n-propoxy, or isopropoxy, and the halogen is, for example, chlorine or bromine, preferably Z is hydroxy, methoxy, ethoxy, n-propoxy, or isopropoxy. A, L, B, D, X １ , X ２ , X ３ , X ４ Y and m are as described in any one of claims 1 to 13. A method for preparing a compound according to any one of claims 1 to 13 or a pharmaceutically acceptable salt thereof, characterized in that

15. A pharmaceutical composition comprising a therapeutically effective amount of substance A and a pharmaceutical excipient, wherein substance A is a compound described in any one of claims 1 to 13 or a pharmaceutically acceptable salt thereof.

16. Use of substance A in the preparation of a muscarinic receptor positive allosteric modulator, wherein substance A is a compound represented by formula I as described in any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition as described in claim 15.

17. Use of substance A in the preparation of a medicament for treating and / or preventing a disease mediated by muscarinic receptors, wherein substance A is a compound represented by formula I as described in any one of claims 1 to 13 or a pharmaceutically acceptable salt thereof, or the medicament composition as described in claim 15, preferably the disease being Parkinson's disease, Alzheimer's disease, Huntington's disease, schizophrenia, or drug addiction.

Images