Imidazopyridine or imidazopyrazine compounds, methods for producing the same, pharmaceutical compositions and their use

Abstract

This invention discloses imidazopyridine or imidazopyrazine compounds, methods for producing the same, pharmaceutical compositions, and uses thereof. This invention provides imidazopyridine or imidazopyrazine compounds, their isotopic derivatives, their nitrogen oxides, their pharmaceutically acceptable salts, their solvates, or solvates of their pharmaceutically acceptable salts. The imidazopyridine or imidazopyrazine compounds provided by this invention are α2 / 3-GABA A It possesses excellent affinity activity and positive regulatory activity towards receptors.

Description

Detailed description of the invention

[0001] This application claims priority to Chinese Patent Application No. 2023104520979, filed on April 24, 2023, and to Chinese Patent Application No. 202310824648X, filed on July 06, 2023. This application incorporates the full text of the above Chinese Patent Applications.

[0002] [Technical Field] This invention relates to imidazopyridine or imidazopyrazine compounds, methods for producing the same, pharmaceutical compositions, and uses thereof.

[0003] [Background technology] Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the mammalian central nervous system. Substances that modulate GABAergic neurotransmission are widely used to treat various conditions such as epilepsy, anxiety disorders, and depression. There are two types of GABA receptors in nature, one of which is a member of the ligand-gated ion channel superfamily. A Receptor (GABA) A R) is one of the two receptors (GABA) which is a member of the G protein-coupled receptor superfamily. B R) is the GABA found in mammals to date. A The receptor subunits include α1-6, β1-4, γ1-3, δ, ε, θ, and ρ1-2, where the α, β, and γ subunits constitute complete functional GABA. A Essential for receptor formation, the α subunit interacts with benzodiazepine compounds and GABA. A It is important for binding to receptors.

[0004] Drugs that bind to allosteric binding sites can be classified into positive allosteric modulators (or positive allosteric regulators) that enhance receptor activity, negative allosteric modulators (or negative allosteric regulators) that reduce receptor activity, or neutral allosteric modulators (compounds that bind to allosteric binding sites but do not regulate receptor activity). Recent evidence suggests that GABA A receptors containing α2 or α3 subunits (referred to herein as α2 / 3-GABA A receptors) may be involved in certain pain states, suggesting that positive allosteric modulators of these receptors may be effective analgesics (Mirza, N. R.; Munro, G., Drug News and Perspectives, 2010, 23(6), 351-360).

[0005] International patent applications PCT / SE2006 / 001433 (published as WO2007 / 073283) and PCT / SE2010 / 050892 (published as WO2011 / 021979) disclose certain quinoline derivatives that are considered to be usable as GABA A R modulators.

[0006] The prevailing view is that the regulatory activity of GABA A receptors containing α1 subunits is the main cause of the side effects (such as sedation, dependence, drowsiness, amnesia, etc.) of current GABA A modulators (such as benzodiazepines) (Rudolph, U.; Frederic Knoflach, F., Nature Reviews: Drug Discovery, 2011, 10(9), 685-697). Finding new compounds that interact with GABA A receptors and have fewer α1-GABA A receptor-related side effects has great therapeutic potential.

[0007] 〔Summary of the Invention〕 The technical problem to be solved by the present invention is GABA in the prior artA Compounds that have a regulatory function on the receptor are α2 / 3-GABA A To address the problem of low affinity activity and positive regulatory activity towards receptors, the present invention provides imidazopyridine or imidazopyrazine compounds, methods for producing the same, pharmaceutical compositions, and uses. The imidazopyridine or imidazopyrazine compounds provided by the present invention are α2 / 3-GABA A It possesses excellent affinity activity and positive regulatory activity towards receptors.

[0008] The present invention solves the above technical problems using the following technical solutions.

[0009] The present invention also provides compounds represented by formula (I), isotopic derivatives thereof, nitrogen oxides thereof, pharmaceutically acceptable salts thereof, solvates thereof, or solvates of pharmaceutically acceptable salts thereof.

[0010] [ka]

[0011] however, R1 and R2 are hydrogen and C, respectively. 1-6 Alkyl, C 3-6 Cycloalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 4-12 member heterocycloalkyl, C 6-10 C substituted with aryl, 5-12 member heteroaryl, or 1, 2, 3, 4, or 5 R9 groups. 1-6 Alkyl, C 3-6 Cycloalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 4-2 member heterocycloalkyl, C 6-10 Aryls are 5-12 member heteroaryls. Alternatively, R1 and R2 are N atoms linked to them and 4-12 member heterocycloalkyl groups, or 1, 2, or 3 R 1-1 Forms a 4-12 member heterocycloalkyl group substituted by R 1-1 These are independently deuterium, -CN, -OH, halogen, and C1-6 Alkyl or -OC 1-6 It is alkyl, R3 and R4 are H, C 1-6 Alkyl, C 3-6 Cycloalkyl, -OC 1-6 Alkyl or 1, 2, or 3 R 3-1 C replaced by 1-6 Alkyl, C 3-6 Cycloalkyl, -OC 1-6 It is alkyl, R 3-1 These are independently deuterium, -CN, -OH, halogen, and C 1-6 Alkyl or -OC 1-6 It is alkyl, R5 and R6 are independently hydrogen, deuterium, halogen, or C 1-6 It is alkyl, X is N or CR8, R8 is hydrogen, deuterium, halogen, -CN, C 1-6 Alkyl, C 3-6 Cycloalkyl, -OC 1-6 Alkyl, or 1, 2, or 3 R 8-1 C replaced by 1-6 Alkyl, C 3-6 Cycloalkyl, -OC 1-6 It is alkyl, R 8-1 These are independently deuterium, -CN, -OH, halogen, and C 1-6 Alkyl or -OC 1-6 It is alkyl, R7 -CN, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkenyl, C 6-10 Aryl, 5-12 member heteroaryl, 5-12 member heterocycloalkyl, 5-12 member heterocycloalkenyl, -Z-(CR a R b ) m -C 6-10 Ariel, -Z-(CR a R b ) m -5-12 member heteroaryl or 1, 2, 3, 4 or 5 R 10 C replaced by 1-6 Alkyl, C3-6 Cycloalkyl, C 3-6 Cycloalkenyl, C 6-10 Aryl, 5- to 12-membered heteroaryl, 5- to 12-membered heterocycloalkyl, 5- to 12-membered heterocycloalkenyl, -Z-(CR a R b ) m -C 6-10 Aryl, -Z-(CR a R b ) m - is 5- to 12-membered heteroaryl, Z is independently -O- or -NR c and R a and R b are independently H or C 1-6 alkyl, and R c is H or C 1-6 alkyl, m is independently 0, 1 or 2, R9 is halogen, -OH, -CN, C 1-6 alkyl, -O-C 1-6 alkyl, C 3-6 cycloalkyl, 5- to 12-membered heterocycloalkyl, C 6-10 aryl or 5- to 12-membered heteroaryl or C substituted by one, two or three R 9-1 alkyl, -O-C 1-6 alkyl, C 1-6 cycloalkyl, 5- to 12-membered heterocycloalkyl, C 3-6 aryl or 5- to 12-membered heteroaryl, and R 6-10 is independently deuterium, -CN, -OH, halogen, C 9-1 alkyl or -O-C 1-6 alkyl, 1-6 and R R 10 is oxo (-C=O), deuterium, halogen, -OH, -CN,

[0012]

Chemical formula

[0013] 、C 1-6 alkyl, C 2-6Alkenyl, C 2-6 Alkynyl, -O-C 1-6 Alkyl, -S-C 1-6 Alkyl, C 6-10 Aryl, 5- to 12-membered heteroaryl, C 3-6 Cycloalkyl, 5- to 12-membered heterocycloalkyl, or C substituted by 1, 2, 3, 4 or 5 Rs 11 by C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -O-C 1-6 Alkyl, -S-C 1-6 Alkyl, C 6-10 Aryl, 5- to 12-membered heteroaryl, C 3-6 Cycloalkyl, 5- to 12-membered heterocycloalkyl, where R 11 is deuterium, halogen, -CN, -OH, C 1-6 Alkyl, -O-C 1-6 Alkyl, or oxo (-C=O), and the 5- to 12-membered heteroaryl is each independently a 5- to 12-membered heteroaryl having 1, 2, 3 or 4 heteroatoms, the type of heteroatom being independently selected from N, O and S; the 4- to 12-membered heterocycloalkyl is each independently a 4- to 12-membered heterocycloalkyl having 1, 2, 3 or 4 heteroatoms, the type of heteroatom being independently selected from N, O and S; the 5- to 12-membered heterocycloalkyl is each independently a 5- to 12-membered heterocycloalkyl having 1, 2, 3 or 4 heteroatoms, the type of heteroatom being independently selected from N, O and S; and the 5- to 12-membered heterocycloalkenyl is each independently a 5- to 12-membered heterocycloalkenyl having 1, 2, 3 or 4 heteroatoms, the type of heteroatom being independently selected from N, O and S.

[0014] The present invention also provides a compound represented by formula (I), an isotope derivative thereof, a nitrogen oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of a pharmaceutically acceptable salt thereof.

[0015] [ka]

[0016] however, R1 and R2 are hydrogen and C, respectively. 1-6 Alkyl, C 3-6 Cycloalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 5-12 member heterocycloalkyl, C 6-10 C substituted with aryl, 5-12 member heteroaryl, or 1, 2, 3, 4, or 5 R9 groups. 1-6 Alkyl, C 3-6 Cycloalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 5-12 member heterocycloalkyl, C 6-10 Aryls are 5-12 member heteroaryls. Alternatively, R1 and R2 form a 5-12 member heterocycloalkyl group with the N atom linked to them. R3 and R4 are H, R5 and R6 are independently hydrogen or methyl. X is N or CR8, R8 is hydrogen, deuterium, halogen, -CN, methoxy, methyl, or -CHF2. R7 -CN, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkenyl, C 6-10 Aryl, 5-12 member heteroaryl, 5-12 member heterocycloalkyl, 5-12 member heterocycloalkenyl, -Z-(CR a R b ) m -C 6-10 A aryl or 1, 2, 3, 4, or 5 R 10 C replaced by 1-6 Alkyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkenyl, C 6-10 Aryl, 5-12 member heteroaryl, 5-12 member heterocycloalkyl, 5-12 member heterocycloalkenyl, -Z-(CR a Rb ) m -C 6-10 It is Ariel, Z is either -O- or -NR c And R a and R b H or C 1-6 It is alkyl, R c is H or C 1-6 It is alkyl, m is 0, 1, or 2. R9 stands for halogen, -OH, -CN, C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 Cycloalkyl, 5-12 member heterocycloalkyl, C 6-10 It is an aryl or a 5-12 member heteroaryl. R 10 oxo (-C=O), deuterium, halogen, hydroxyl, -CN,

[0017] [ka]

[0018] , C 1-6 Alkyl, C 2-6 Alkinyl, -OC 1-6 Alkyl, -SC 1-6 Alkyl, 5-12 member heteroaryl, C 3-6 Cycloalkyl, 5-12 member heterocycloalkyl, or 1, 2, 3, 4 or 5 R 11 C replaced by 1-6 Alkyl, C 2-6 Alkinyl, -OC 1-6 Alkyl, -SC 1-6 Alkyl, 5-12 member heteroaryl, C 3-6 Cycloalkyl, 5-12 member heterocycloalkyl, R 11 is halogen, -CN, -OH, C 1-6 It is alkyl or oxo (-C=O), Each of the 5-12 member heteroaryls is independently a 5-12 member heteroaryl having one, two, or three heteroatoms, and the type of heteroatom is independently selected from N, O, and S; each of the 5-12 member heterocycloalkyls is independently a 5-12 member heterocycloalkyl having one, two, or three heteroatoms, and the type of heteroatom is independently selected from N, O, and S; each of the 5-12 member heterocycloalkenyls is independently a 5-12 member heterocycloalkenyl having one, two, or three heteroatoms, and the type of heteroatom is independently selected from N, O, and S.

[0019] The present invention provides compounds represented by formula (I), their isotopic derivatives, their nitrogen oxides, their pharmaceutically acceptable salts, their solvates, or solvates of their pharmaceutically acceptable salts.

[0020] [ka]

[0021] however, R1, R2, R3, and R4 are each independently hydrogen and C 1-6 Alkyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyl C 1-3 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-6 Heterocycloalkyl, C 3-6 Heterocycloalkyl C 1-3 Alkyl, aryl, heteroaryl, aryl C 1-3 Alkyl, heteroaryl C 1-3 The alkyl group is optionally substituted with 1, 2, 3, 4, or 5 R9 groups. Alternatively, R1 and R2 are connected to form a ring, and R3 and R4 are connected to form a ring. X is selected from N, CR8. R5, R6, and R8 are independently hydrogen, halogen, cyanoacrylate, and carbon dioxide. 1-6 Alkyl, C 1-6Alkoxy, C 1-6 Haloalkyl, C 1-6 It is a haloalkoxy, R7 each operates independently C 6-10 Ariel, C 6-10 Aryloxy, C 2-9 Heteroaryl, C 2-9 Heteroaryloxy, cycloalkyl, heterocycloalkyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Arylamine, C 2-9 Heteroarylamine, C 2-9 Heteroaryl C 1-3 Alkoxy, C 6-10 Aryl C 1-3 The alkoxy group is an alkoxy group in which each of the R groups can be optionally 1, 2, 3, 4, or 5. 10 Replaced by, R9 stands for halogen, oxo, hydroxy, cyano, nitro, C 1-6 Alkyl, C 1-6 It is an alkoxy, R 10 These are halogens, oxo, hydroxy, cyano, nitro, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Haloalkoxy, C 2-6 Alkenil, C 2-6 Alkinyl, -OR 12 , -S(O) n R 11 , -NR 11 R 12 , -C(O)R 11 ,-COOR 11 -OC(O)R 11 , -NR 12 C(O)R 11 -C(O)NR 11 R 12 , -NR 12 C(O)OR 11 -OC(O)NR 11 R 12 , -NR 12 S(O) n R 11 , -S(O) nNR 11 R 12 , amino, C 1-4 Alkylamino, C 2-8 Dialkylamino, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocycloalkylalkyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl, where the C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocycloalkylalkyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl each independently comprises 1, 2, 3, 4, or 5 halogens, oxo, hydroxy, cyano, nitro, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Haloalkoxy, C 2-6 Alkenil, C 2-6 Alkinyl, -OR 11 , -S(O) n R 11 , -NR 11 R 12 , -C(O)R 11 ,-COOR 11 -OC(O)R 11 , -NR 12 C(O)R 11 -C(O)NR 11 R 12 , -NR 12 C(O)OR 11 -OC(O)NR 11 R 12 , -NR 12 S(O) n R 11 , -S(O) n NR 11 R 12 It is optionally replaced by a base selected from, R 11 , R 12 Hydrogen and C are independent of each other. 1-6 Alkyl, C 1-6 Haloalkyl, aryl, heteroaryl, heteroaryl C 1-4Alkyl, aryl C 1-4 Selected from alkyl, cycloalkyl, heterocycloalkyl, and heterocycloalkylalkyl. n is either 1 or 2.

[0022] The present invention provides compounds represented by formula (I), their isotopic derivatives, their nitrogen oxides, their pharmaceutically acceptable salts, their solvates, or solvates of their pharmaceutically acceptable salts.

[0023] [ka]

[0024] however, R1 and R2 are hydrogen and C, respectively, independently. 1-6 Alkyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyl C 1-3 Alkyl, C 2-6 It is an alkenyl, and each of the aforementioned groups is optionally substituted with 1, 2, 3, 4, or 5 R9 groups. R3, R4, R5, and R6 are all hydrogen. X is selected from N, CR8. R8 is selected from substituents that are hydrogen, halogen, or cyano. R7 each operates independently C 6-10 Ariel, C 6-10 Aryloxy, C 2-9 Heteroaryl, C 2-9 Heteroaryloxy, cycloalkyl, heterocycloalkyl, C 6-10 Arylamine, C 2-9 Heteroarylamine, C 2-9 Heteroaryl C 1-3 Alkoxy, C 6-10 Aryl C 1-3 It is an alkoxy, and each of the groups is 1, 2, 3, 4, or 5 R 10 It is arbitrarily replaced by R9 is halogen, R 10 Deuterium, halogen, hydroxyl, cyano, C1-6 Alkyl, C 1-6 The C is an alkoxy, cycloalkyl, or heterocycloalkyl, where the C 1-6 The alkyl, cycloalkyl, or heterocycloalkyl group is each arbitrarily selected from 1, 2, 3, 4, or 5 independent substituents that are halogen, oxo, hydroxy, or cyano.

[0025] In one preferred embodiment, in a compound represented by formula (I), its isotopic derivative, its nitrogen oxide, its pharmaceutically acceptable salt, its solvate, or a pharmaceutically acceptable salt thereof, the definitions of some groups are as described below, and the definitions of other groups are as described in some embodiments of the present invention (hereinafter referred to as "in one preferred embodiment"), where R1 is H.

[0026] In one preferred embodiment, R2 is C 1-6 Alkyl, C 3-6 Cycloalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 4-2 member heterocycloalkyl, C 6-10 C substituted with aryl, 5-12 member heteroaryl, or 1, 2, 3, 4, or 5 R9 groups. 1-6 Alkyl, C 3-6 Cycloalkyl, C 2-6 These are alkenyls, 4-12 member heterocycloalkyls, and 5-12 member heteroaryls.

[0027] In one preferred embodiment, R 1-1 is C 1-6 It is alkyl.

[0028] In one preferred embodiment, R3 and R4 are H.

[0029] In one preferred embodiment, R8 is hydrogen, deuterium, halogen, -CN, C 1-6 Alkyl, -OC 1-6 Alkyl or 1, 2, or 3 R 8-1 C replaced by 1-6It is alkyl.

[0030] In one preferred embodiment, R7 is -CN, C 1-6 Alkyl, C 3-6 Cycloalkenyl or 1, 2, 3, 4 or 5 R 10 C replaced by 6-10 Aryl, 5-12 member heteroaryl, 5-12 member heterocycloalkyl, 5-12 member heterocycloalkenyl, -Z-(CR a R b ) m -C 6-10 It is Ariel.

[0031] In one preferred embodiment, R a and R b H is H.

[0032] In one preferred embodiment, Z is -O-.

[0033] In one preferred embodiment, m is 0 or 1.

[0034] In one preferred embodiment, R9 is a halogen, -OH, -CN, C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 Cycloalkyl, 5-12 member heterocycloalkyl, C 6-10 Aryl or 5-12 member heteroaryl, or 1, 2 or 3 R 9-1 It is a 5- to 12-membered heteroaryl substituted by [the specified compound].

[0035] In one preferred embodiment, R 9-1 C is independent 1-6 It is alkyl.

[0036] In one preferred embodiment, R 10 oxo (-C=O), deuterium, halogen, -OH, -CN,

[0037] [ka]

[0038] , C 1-6 Alkyl, C 2-6 Alkinyl, -OC 1-6 Alkyl, -SC 1-6 Alkyl, 5-12 member heteroaryl, C 3-6 Cycloalkyl, 5-12 member heterocycloalkyl, or 1, 2, 3, 4 or 5 R 11 C replaced by 1-6 Alkyl, C 2-6 Alkinyl, -OC 1-6 Alkyl, -SC 1-6 Alkyl, 5-12 member heteroaryl, C 3-6 They are cycloalkyl and 5-12 member heterocycloalkyl.

[0039] In one preferred embodiment, R 11 Deuterium, halogen, -CN, -OH, C 1-6 It is alkyl or oxo (-C=O).

[0040] In one preferred embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 1-1 , R 3-1 , R 8-1 , R 9-1 , R a and R b And the aforementioned C 1-6 C substituted with alkyl 1-6 C in alkyl 1-6 Alkyl is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or tert-butyl, for example, methyl, ethyl, n-butyl, or isobutyl.

[0041] In one preferred embodiment, R1, R2, R3, R4, R7, R8, R9 and R 10 And the aforementioned C 3-6 Cycloalkyl and substituted C 3-6 C in cycloalkyl 3-6Cycloalkyls are independently cyclopropyl, cyclobutyl, cyclopentyl,

[0042] [ka]

[0043] Alternatively, it is cyclohexyl.

[0044] In one preferred embodiment, R1, R2 and R 10 And the aforementioned C 2-6 C substituted with alkenyl 2-6 C in alkenil 2-6 Alkenyls are independently vinyl, n-propenyl, isopropenyl, n-butenyl, or isobutenyl.

[0045] In one preferred embodiment, R1, R2 and R 10 And the aforementioned C 2-6 Alkynyl-substituted C 2-6 C in alkinyl 2-6 Alkynnyl is independently ethynyl, n-propynyl, or n-butynyl.

[0046] In one preferred embodiment, R1, R2, R7, R8, R9, R 10 and R 11 And the aforementioned C 6-10 C substituted with aryl 6-10 C in Aryl 6-10 The aryl group is independently phenyl or naphthyl, for example, phenyl.

[0047] In one preferred embodiment, R3, R4, R8, R9, R 10 , R 11 , R 1-1 , R 3-1 , R 8-1 and R 9-1 And the aforementioned -OC 1-6 Alkyl-substituted -OC 1-6 C in alkyl 1-6Alkyl is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or tert-butyl, for example, methyl, ethyl, n-propyl, or isopropyl.

[0048] In one preferred embodiment, R3, R4, R5, R6, R8, R9, R 10 , R 11 , R 1-1 , R 3-1 , R 8-1 and R 9-1 The halogen is independently F, Cl, or Br, for example, F or Cl.

[0049] In one preferred embodiment, R1 and R2, the 4-12 member heterocycloalkyls in the 4-12 member heterocycloalkyls substituted with 1, 2, 3, 4, or 5 R9s are independently 4-6 member heterocycloalkyls.

[0050] In one preferred embodiment, R1 and R2 are the 4-12 member heterocycloalkyls substituted with 1, 2, 3, 4, or 5 R9s, where each 4-12 member heterocycloalkyl independently has 1, 2, or 3 heteroatoms, and the heteroatom type is N, for example,

[0051] [ka]

[0052] That is the case.

[0053] In one preferred embodiment, R1 and R2, the 5-12 member heteroaryls in the 5-12 member heteroaryls substituted with 1, 2, 3, 4 or 5 R9s are independently 5-6 member heteroaryls.

[0054] In one preferred embodiment, R1 and R2, the 5-12 member heteroaryls in the 5-12 member heteroaryls substituted with 1, 2, 3, 4, or 5 R9 independently have 1, 2, or 3 heteroatoms, and the types of heteroatoms are selected from N and O to form a 5-12 member heteroaryl, for example,

[0055] [ka]

[0056] That is the case.

[0057] In one preferred embodiment, R1 and R2 are linked to an N atom and a 4-12 member heterocycloalkyl or 1, 2, or 3 R 1-1 When forming a 4-12 member heterocycloalkyl group substituted with R, the 4-12 member heterocycloalkyl group and 1, 2, or 3 R 1-1 In 4-12 member heterocycloalkyl groups substituted by , the 4-12 member heterocycloalkyl groups are independently 4-6 member heterocycloalkyl groups.

[0058] In one preferred embodiment, R1 and R2 are linked to an N atom and a 4-12 member heterocycloalkyl or 1, 2, or 3 R 1-1 When forming a 4-12 member heterocycloalkyl group substituted with R, the 4-12 member heterocycloalkyl group and 1, 2, or 3 R 1-1 In 4-12 member heterocycloalkyls substituted by , each 4-12 member heterocycloalkyl independently has one, two, or three heteroatoms, and the heteroatom type is N. For example,

[0059] [ka]

[0060] That is the case.

[0061] In one preferred embodiment, at R7, the C 3-6 Cycloalkenyl and 1, 2, 3, 4 or 5 R 10 C replaced by 3-6 C in cycloalkenyl 3-6 Cycloalkenyls are independently cyclopropenyl, cyclobutenyl, cyclopentenyl, or cyclohexenyl, for example, cyclohexenyl, and furthermore, for example,

[0062] [ka]

[0063] That is the case.

[0064] In one preferred embodiment, R7 contains the 5-12 member heteroaryl and 1, 2, 3, 4, or 5 R 10 In 5-12 member heteroaryls substituted by , each 5-12 member heteroaryl independently has one, two, or three heteroatoms, and the types of heteroatoms are selected from N and O, for example,

[0065] [ka]

[0066] That is the case.

[0067] In one preferred embodiment, R7 is the 5-12 member heterocycloalkyl and 1, 2, 3, 4 or 5 R 10 In 5-12 member heterocycloalkyl groups substituted by , each 5-12 member heterocycloalkyl group is independently a 5-6 member heterocycloalkyl group.

[0068] In one preferred embodiment, R7 is the 5-12 member heterocycloalkyl and 1, 2, 3, 4 or 5 R 10In 5-12 member heterocycloalkyls substituted by , each 5-12 member heterocycloalkyl independently has one, two, or three heteroatoms, and the type of heteroatom is selected from N and O, for example,

[0069] [ka]

[0070] That is the case.

[0071] In one preferred embodiment, R7 contains the 5-12 member heterocycloalkenyl and 1, 2, 3, 4 or 5 R 10 In 5-12 member heterocycloalkenyls substituted with , the 5-12 member heterocycloalkenyls are independently 5-6 member heterocycloalkyls.

[0072] In one preferred embodiment, R7 contains the 5-12 member heterocycloalkenyl and 1, 2, 3, 4 or 5 R 10 In 5-12 member heterocycloalkenyls substituted by , each 5-12 member heterocycloalkenyl independently has one, two, or three heteroatoms, and the heteroatom type is N, which is a 5-12 member heterocycloalkyl, for example,

[0073] [ka]

[0074] That is the case.

[0075] In one preferred embodiment, at R7, the -Z-(CR a R b ) m -C 6-10 Aaryl and 1, 2, 3, 4 or 5 R 10 -Z-(CR) a R b ) m -C 6-10 -Z-(CR) in aryla R b ) m -C 6-10 Ariel is independent

[0076] [ka]

[0077] That is the case.

[0078] In one preferred embodiment, R9 contains the 5-12 member heteroaryl and 1, 2, or 3 R 9-1 In 5-12 member heteroaryls substituted by this compound, the 5-12 member heteroaryls are independently 5-6 member heteroaryls.

[0079] In one preferred embodiment, R9 contains the 5-12 member heteroaryl and 1, 2, or 3 R 9-1 In 5-12 member heteroaryls substituted by , each 5-12 member heteroaryl independently has one, two, or three heteroatoms, and the types of heteroatoms are selected from N and O, for example,

[0080] [ka]

[0081] That is the case.

[0082] In one preferred embodiment, R 10 Then, the aforementioned 5-12 member heteroaryl and 1, 2, or 3 R 9-1 In 5-12 member heteroaryls substituted by , each 5-12 member heteroaryl independently has one, two, three, or four heteroatoms, and the types of heteroatoms are selected from N and O, for example,

[0083] [ka]

[0084] That is the case.

[0085] In one preferred embodiment, R 10 Then, the aforementioned 5-12 member heterocycloalkyl and 1, 2, or 3 R 9-1 In 5-12 member heterocycloalkyl groups substituted by , each 5-12 member heterocycloalkyl group is independently a 5-6 member heterocycloalkyl group.

[0086] In one preferred embodiment, R 10 Then, the aforementioned 5-12 member heterocycloalkyl and 1, 2, or 3 R 9-1 In 5-12 member heterocycloalkyls substituted by , each 5-12 member heterocycloalkyl independently has one, two, or three heteroatoms, and the type of heteroatom is selected from N and O, for example,

[0087] [ka]

[0088] That is the case.

[0089] In one preferred embodiment, R 10 And, the aforementioned -SC 1-6 Alkyl and 1, 2, 3, 4 or 5 R 11 -SC replaced by 1-6 C in alkyl 1-6 Alkyl is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or tert-butyl, for example, methyl.

[0090] In one preferred embodiment, R2 is

[0091] [ka]

[0092] That is the case.

[0093] In one preferred embodiment, R1 and R2 are N atoms linked to them and

[0094] [ka]

[0095] It forms.

[0096] In one preferred embodiment, R5 is H, deuterium, or methyl.

[0097] In one preferred embodiment, R6 is H, deuterium, F, or methyl.

[0098] In one preferred embodiment,

[0099] [ka]

[0100] teeth

[0101] [ka]

[0102] That is the case.

[0103] In one preferred embodiment, R7 is

[0104] [ka] TIFF2026516799000025.tif207169

[0105] That is the case.

[0106] In one preferred embodiment, R8 is H, D, F, Cl, -CN, -CH3, -OCH3, or -CHF2.

[0107] In one preferred embodiment, R9 is F, -OH, -CN, methyl, methoxy, cyclopropyl, phenyl

[0108] [ka]

[0109] That is the case.

[0110] In one preferred embodiment, R 10 oxo (-C=O), deuterium, F, Cl, -OH, -CN,

[0111] [ka]

[0112] methyl, methoxy, -CF3,

[0113] [ka]

[0114] That is the case.

[0115] In one preferred embodiment, R 11 These are deuterium, F, -CN, methyl, ethyl, or oxo (-C=O).

[0116] In one preferred embodiment,

[0117] [ka]

[0118] teeth

[0119] [ka]

[0120] (for example,

[0121] [ka]

[0122] ) and R7

[0123] [ka]

[0124] That is the case.

[0125] In some embodiments, the compound represented by formula (I) is selected from one of the following compounds.

[0126] [Table 1] TIFF2026516799000034.tif220169TIFF2026516799000035.tif225169TIFF2026516799000036.tif246169TIFF202 6516799000037.tif225169TIFF2026516799000038.tif224169TIFF2026516799000039.tif242169TIFF20265167990 00040.tif228169TIFF2026516799000041.tif226169TIFF2026516799000042.tif233169TIFF2026516799000043.t if224169TIFF2026516799000044.tif231169TIFF2026516799000045.tif235169TIFF2026516799000046.tif221169

[0127] GABA (Invention) AThe present invention provides the use of the above-mentioned substance X or the above-mentioned pharmaceutical composition in the manufacture of a pharmaceutical for the treatment or prevention of receptor-related diseases, wherein substance X is a compound described in any one of the above embodiments, an isotopic derivative thereof, a nitrogen oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof.

[0128] Furthermore, the aforementioned GABA A Receptor-related disorders are selected from pain, Alzheimer's disease, multiple infarct dementia, stroke, epilepsy, anxiety disorders, pruritus, and depression.

[0129] Furthermore, the aforementioned GABA A Receptor-related diseases are caused by α2 / 3-GABA A Receptor-related disorders include, for example, pain, epilepsy, anxiety, itching, and depression.

[0130] The present invention provides the use of the substance X or the pharmaceutical composition in the manufacture of a pharmaceutical, the pharmaceutical being used for the treatment or prevention of pain, Alzheimer's disease, multiple infarct dementia, stroke, pain, epilepsy, anxiety, itching, or depression.

[0131] GABA (Invention) A The present invention provides the use of substance X or the pharmaceutical composition in the treatment or prevention of receptor-related diseases.

[0132] Furthermore, the aforementioned GABA A Receptor-related disorders are selected from pain, Alzheimer's disease, multiple infarct dementia, and stroke.

[0133] Furthermore, the aforementioned GABA A Receptor-related diseases are caused by α2 / 3-GABA A Receptor-related disorders include, for example, pain, epilepsy, anxiety, itching, and depression.

[0134] The present invention provides for the use of substance X or the pharmaceutical composition in the treatment or prevention of pain, Alzheimer's disease, multiple infarct dementia, stroke, epilepsy, anxiety, itching, or depression.

[0135] This invention relates to GABA A The present invention provides a method for treating or preventing receptor-related diseases, the method comprising the step of administering the above substance X or the above pharmaceutical composition to an individual in need.

[0136] Furthermore, the aforementioned GABA A Receptor-related disorders are selected from pain, Alzheimer's disease, multiple infarct dementia, and stroke.

[0137] Furthermore, the aforementioned GABA A Receptor-related diseases are caused by α2 / 3-GABA A Receptor-related disorders include, for example, pain, epilepsy, anxiety, itching, and depression.

[0138] The present invention provides a method for treating or preventing a disease, comprising the step of administering the above substance X or the above pharmaceutical composition to an individual in need.

[0139] The aforementioned conditions include pain, Alzheimer's disease, multiple infarct dementia, stroke, epilepsy, anxiety, pruritus, or depression.

[0140] Unless otherwise specified, the terms used in this invention have the following meanings: Unless otherwise specified, the following definitions are intended to explain and define the meaning and scope of various terms used herein in describing the present invention.

[0141] The following definitions of general terms apply whether they are used alone or in combination.

[0142] The nomenclature used herein follows the IUPAC system nomenclature. Open valence bonds appearing on carbon, oxygen, sulfur, or nitrogen atoms in the structures shown herein indicate the presence of a hydrogen atom.

[0143] As used herein, “patient” is defined as any warm-blooded animal, including but not limited to mice, guinea pigs, dogs, horses, or humans, and the patient is most preferably a human.

[0144] The term "halogen" refers to fluorine, chlorine, bromine, and iodine, and preferably fluorine.

[0145] The term "alkyl" refers to a group consisting only of carbon and hydrogen atoms, with a specified number of carbon atoms (for example, C 1-6 , more C 1-4 This refers to a saturated linear or branched hydrocarbon group having ) ). Alkyl includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, or n-hexyl.

[0146] The term "alkenyl" refers to a straight-chain or branched-chain hydrocarbon group having at least one double bond, consisting only of carbon and hydrogen atoms, and a specific number of carbon atoms (e.g., C 2-6 And, more C 2-4 Alkenyls include, but are not limited to, vinyl (-CH=CH2), propenyl (-CH=CH-CH3), allyl (-CH2-CH=CH2), isopropenyl (-C(CH3)=CH2), -CH=CH-CH2-CH3, -CH2-CH=CH-CH3, -CH=CH-CH2-CH2-CH3, -CH2-CH=CH-CH2-CH3, -CH=CH-CH2-CH3, -CH=CH-CH(CH3)2, -CH2-CH=C(CH3)2, or -CH=CH-(CH2)3-CH3.

[0147] The term "alkynyl" refers to a linear or branched hydrocarbon group having at least one triple bond, consisting only of carbon and hydrogen atoms, and a specified number of carbon atoms (e.g., C 2-6 And moreover, C 2-4Alkynnyls include, but are not limited to, ethynyl (-C≡CH), propynyl (-C≡C-CH3), -C≡C-CH2-CH3, -CH2C≡C-CH3, -C≡C-CH2-CH2-CH3, -CH2C≡C-CH2-CH3, -C≡C-CH2-CH2-CH2-CH3, -C≡C-CH2-CH2-CH2-CH3, -C≡C-CH2-CH(CH3)2, -C≡CC(CH3)3, -C≡C-CH(CH3)2, or -CH2C≡C-CH2-CH2-CH3.

[0148] The term "alkoxy" refers to the group -OR, where R is alkyl.

[0149] The term "cycloalkyl" refers to a saturated monocyclic cyclic group having a specified number of carbon atoms (e.g., C3-C6) and consisting solely of carbon atoms. Cycloalkyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0150] The term "heterocycloalkyl" refers to a saturated cyclic group having a specified number of ring atoms (e.g., 5 to 12), a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified number of heteroatoms (1, 2, or 3 types of N, O, and S).

[0151] The term "heterocycloalkenyl" refers to an unsaturated cyclic group having a specified number of ring atoms (e.g., 5 to 12), a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified number of heteroatoms (1, 2, or 3 types of N, O, and S).

[0152] The term "heteroaryl" refers to a cyclic group having a specified number of ring atoms (e.g., 5-12 members, 5-10 members, preferably 6-10 members, more preferably 5-8 members), a specified number of heteroatoms (e.g., 1, 2, 3, or 4), and a specified type of heteroatom (1, 2, or 3 of N, O, and S), which may be monocyclic or bicyclic, and at least one ring is aromatic (according to Hückel's rule). The aryl is bonded to other fragments within the molecule via an aromatic or non-aromatic ring.

[0153] The term "aryl" refers to a specific number of carbon atoms (for example, C6-C6). 10 aryls refer to cyclic groups consisting only of carbon atoms, which are monocyclic or polycyclic, and at least one ring is aromatic (according to the Shock-Soul rule). Aryls are attached to other fragments within the molecule via aromatic or non-aromatic rings. Aryls include, but are not limited to, phenyl and naphthyl, for example,

[0154] [ka]

[0155] That is the case.

[0156] In the definition of a compound, any variable (e.g., group R) 11 If the R(R) appears multiple times, their definitions are independent of each other and do not affect each other. For example, three R(R) 11 Phenyl substituted by has three R 11 Substituted by, three R 11 The definitions are mutually independent and do not influence each other.

[0157] The term "pharmaceutically acceptable salt" refers to a salt obtained by reacting a compound with a pharmaceutically acceptable (relatively non-toxic, safe, and suitable for patient use) acid or base. If the compound contains relatively acidic functional groups, a base addition salt can be obtained by contacting a sufficient amount of a pharmaceutically acceptable base with the free form of the compound in a suitable inert solvent. If the compound contains relatively basic functional groups, an acid addition salt can be obtained by contacting a sufficient amount of a pharmaceutically acceptable acid with the free form of the compound in a suitable inert solvent. For specifics, refer to Handbook of Pharmaceutical Salts: Properties, Selection, and Use (P. Heinrich Stahl, 2002).

[0158] The term "solvate" refers to a substance formed after a compound and solvent have been crystallized. Solvates are classified into stoichiometric solvates and non-stoichiometric solvates.

[0159] The term "pharmaceutically acceptable salt solvate" refers to a substance formed by combining a compound with a pharmaceutically acceptable (relatively non-toxic, safe, and suitable for patient use) acid or base or solvent, where "pharmaceutically acceptable salt" has the same meaning as "pharmaceutically acceptable salt" above, and the solvent can be stoichiometric or non-stoichiometric. Pharmaceutically acceptable salt solvates include, but are not limited to, hydrochloride monohydrates.

[0160] The term "pharmaceutical excipients" refers to excipients and additives used in the manufacture and formulation of pharmaceuticals, encompassing all substances contained in drug preparations except for the active ingredient. For further details, refer to the Pharmacopoeia of the People's Republic of China (2020 edition) or the Handbook of Pharmaceutical Excipients (Raymond C Rowe, 2009).

[0161] The term “treatment” refers to any of the following situations: (1) improving one or more biological expressions of a disease; (2) disrupting one or more points in the biological cascade leading to the disease; or (3) delaying the progression of the development of one or more biological expressions of the disease.

[0162] The term "prevention" refers to reducing the risk of developing a disease.

[0163] The present invention also includes isotope-labeled compounds of the present invention. An “isotope-labeled” or “radio-labeled” compound is a compound of the present invention in which one or more atoms are substituted or replaced with atoms having an atomic mass or mass number different from those commonly found in nature (i.e., naturally occurring). Suitable radionuclides that can be incorporated into the compounds of the present invention include: 2 H (also written as D, representing deuterium), 3 H (also written as T, representing tritium), 11 C, 13 C, 14 C, 13 N, 15 N, 15 O, 17 O, 18 O, 18 F, 35 S, 36 Cl, 82 Br, 75 Br, 76 Br, 77 Br, 123 I, 124 I, 125 I and 131 This includes, but is not limited to, I. The radionuclides incorporated into these radiolabeled compounds vary depending on the specific application of the radiolabeled compound. For example, in the case of in vitro receptor labeling and competitive measurements, 3 H, 14 C, 82 Br, 125 I, 131 I or 35 Compounds incorporating sulfur are generally the most useful. In use in radioimaging, 11 C, 18 F, 125 I,123 I, 124 I, 131 I, 75 Br, 76 Br or 77 Br is the most useful.

[0164] It can be understood that a "radiolabeled compound" is a compound that incorporates at least one radionuclide. In some embodiments, the radionuclide is: 3 H, 14 C, 125 I, 35 S and 82 Selected from Br.

[0165] Compounds containing an amine functional group and / or a nitrogen-containing heteroaryl can form N-oxides. Compounds containing an amine functional group and / or a nitrogen-containing heteroaryl according to this application can also form N-oxides.

[0166] When a compound contains multiple amine functional groups and / or nitrogen-containing heteroaryl groups, one or more nitrogen atoms can be oxidized to N-oxides. Specific examples of N-oxides include N-oxides of tertiary amines or N-oxides of nitrogen atoms in nitrogen-containing heterocycles.

[0167] N-oxides can be produced by treating the corresponding amine with an oxidizing agent (e.g., hydrogen oxide or peracid (e.g., peroxycarboxylic acid)), see, for example, Advanced Organic Chemistry, by Jerry March, 4th Edition, Wiley Interscience. More specifically, N-oxides can be produced by the method of LW Deady (Syn. Comm., 1977, 7, 509-514), in which a nitrogen-containing compound is reacted with metachloroperbenzoic acid (m-CPBA) in an inert solvent (e.g., dichloromethane).

[0168] The aforementioned preferred conditions can be combined in any way, without violating the ordinary knowledge of the art, to obtain each preferred embodiment of the present invention.

[0169] The reagents and raw materials used in this invention are commercially available.

[0170] Positive progressive effect of the present invention: The compounds of the present invention possess important pharmacological properties, including α2 / 3-GABA A It is a positive allosteric regulator of the receptor. The compound of the present invention is α2 / 3-GABA A It possesses excellent affinity and positive regulatory activity towards receptors.

[0171] [Modes for carrying out the invention] The present invention will be further described below with reference to embodiments, but this does not limit the present invention to the scope of the above embodiments. In the following embodiments, experimental methods for which specific conditions are not described are selected according to conventional methods and conditions or according to the product description.

[0172] General route

[0173] [ka]

[0174] Method for synthesizing intermediate iv: (using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylate ethyl as an example) Route 1: Step 1: 8-Bromoimidazo[1,2-a]pyridine-2-carboxylate ethyl ester 3-Bromopyridine-2-amine (50 g, 290.6 mmol) and ethyl bromopyruvate (169.2 g, 872 mmol) were sequentially added to anhydrous ethanol (300 mL) and refluxed for 3 hours. The mixture was concentrated, saturated sodium carbonate aqueous solution (300 mL) was added, and extraction was performed with dichloromethane (300 mL x 3). The organic phase was dried over sodium sulfate and concentrated. The target product was obtained by column chromatography (petroleum ether:ethyl acetate = 3:1~1:3), which was a yellowish-brown solid (50 g, 64%). LC-MS: m / z [M+H] + = 269.

[0175] Step 2: 8-Bromo-3-nitroimidazo[1,2-a]pyridine-2-carboxylate ethyl ester Under ice bath conditions, 8-bromoimidazo[1,2-a]pyridine-2-carboxylate ethyl (50 g, 186.6 mmol) was added in batches to concentrated sulfuric acid (200 mL) and dissolved by stirring. Maintaining a low temperature, fuming nitric acid (20 mL) was slowly added dropwise. After the dropwise addition was complete, the reaction was allowed to proceed at room temperature for 2 hours. The reaction solution was poured into ice water, slowly adjusted to pH=6 with sodium hydroxide, extracted with dichloromethane (300 mL x 3), the organic phase was dried over sodium sulfate, and concentrated to obtain the target product, which was a yellow solid (51 g, 87%). LC-MS: m / z [M+H] + =314.

[0176] Step 3: 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylate ethyl ester Ethyl 8-bromo-3-nitroimidazo[1,2-a]pyridine-2-carboxylate (51 g, 163 mmol) was dissolved in methanol (300 mL), zinc powder (53 g, 815 mmol) and saturated ammonium chloride aqueous solution (100 mL) were added, and the mixture was reacted at 50°C for 1 hour. The mixture was filtered to remove the zinc powder, most of the methanol was evaporated, 300 mL of water was added, and the mixture was extracted with ethyl acetate (300 mL x 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and the target product was obtained by column chromatography as a yellow solid (15 g, 32.5%). LC-MS: m / z [M+H] + = 284.

[0177] Route 2: Step 1: 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylate ethyl ester 72 mg, 0.42 mmol of 3-bromopyridine-2-amine was dispersed in 3 mL of anhydrous tetrahydrofuran. 64 mg, 0.63 mmol of 2-oxoethyl acetate and 47 mg, 0.42 mmol of triethylenediamine (CAS No. 280-57-9) were added sequentially. Trimethylsilyl cyanide (CAS No. 7677-24-9, 50 mg, 1.2 mmol) was added at -10°C, and the mixture was heated in a microwave oven at 120°C for 2 hours. 20 mL of water was added, and the mixture was extracted with ethyl acetate (20 mL x 3). The mixture was concentrated and purified by column chromatography (petroleum ether:ethyl acetate = 2:1) to obtain ethyl 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylate, which was a yellow solid (60 mg, 50%). LC-MS: m / z [M+H] + = 284.

[0178] Method for synthesizing intermediate vi: (Using 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide as an example) Route 1: Step 1: 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylate ethyl (1.3 g, 4.59 mmol) and sodium hydroxide aqueous solution (4N, 5 mL) were sequentially added to MeOH (30 mL), and the mixture was stirred at 25°C for 3 hours. The solution was neutralized to pH=6 with 1 M dilute hydrochloric acid, methanol was evaporated, the mixture was filtered, and the cake was dried to obtain the target compound (842 mg, 72%), which was a brown powder. LC-MS: m / z [M+H] + = 256.

[0179] Step 2: 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (842 mg, 3.3 mmol) was dispersed in N,N-dimethylformamide (10 mL). HATU (CAS No.: 148893-10-1, 1.5 g, 3.96 mmol), n-propylamine (383 mg, 6.6 mmol), and triethylamine (660 mg, 6.6 mmol) were added sequentially, and the mixture was stirred for 16 hours. The reaction solution was poured into water, extracted with dichloromethane (50 mL x 3), dried, and concentrated to obtain the title compound (625 mg, 64%, crude product), which was a yellow solid. LC-MS: m / z [M+H] + = 297.

[0180] Route 2: Step 1: 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylate ethyl (1 g, 3.53 mmol) was added to n-propylamine (30 mL), the tube was sealed, and the mixture was stirred at 100°C for 3 hours. The mixture was cooled, concentrated, and the target compound (627 mg, 60%) was obtained by column chromatography (petroleum ether:ethyl acetate = 1:1~1:3), which was a brown solid. LC-MS: m / z [M+H] + = 297.

[0181] The substituents for the starting raw materials of intermediates iv and vi include, but are not limited to, R5=R6=R8=H or R8=F, R5=H, R6=H or R8=Me, R5=H, R6=H or R8=H, R5=Me, R6=H or R8=H, R5=H, R6=Me or R8=CHF2, and R5=H and R6=H can be prepared by the method described above.

[0182] A common synthesis method for compound vii: (using 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide as an example) 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol), (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol), cesium carbonate (221 mg, 0.68 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II) dichloride (CAS No.: 95408-45-0, 26 mg, 0.04 mmol) were sequentially added to a mixture of dioxane and water (2 mL / 0.4 mL), and the mixture was stirred at 100°C for 2 hours under the protection of argon gas. 20 mL of water was added, and the mixture was extracted with dichloromethane (20 mL x 3). The organic phase was concentrated, and the target product (80 mg, 69%) was obtained by column chromatography (petroleum ether:ethyl acetate = 1:1 to 1:5), which was a yellow solid.

[0183] 1 H NMR (400 MHz, DMSO-d6) 8.15 (d, J =5.87 Hz, 1H) 7.55 - 7.63 (m, 1H) 7.39 - 7.48 (m, 1H) 6.82 - 7.03 (m, 4H) 6.15 (s, 2H) 3.70 (s, 3H) 3.13-3.17(m, 2H) 1.44-1.48 (m, 2H) 0.81 (t, J =7.34 Hz, 3H). LC-MS: m / z [M+1] + = 343.

[0184] Example 1

[0185] [ka]

[0186] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-methylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-methylimidazo[1,2-a]pyridine-2-carboxamide 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylate ethyl (100 mg, 0.35 mmol) was added to a methylamine ethanol solution (20%, 3 mL), the tube was sealed, stirred at 110°C for 2 hours, concentrated, and purified by column chromatography to obtain a pale yellow powder (70 mg, 70%). LC-MS: m / z [M+H] + = 270.

[0187] Step 2: Using the same procedure as in the synthesis example of compound vii, the target product (16 mg, 19%) was obtained from 3-amino-8-bromo-N-methylimidazo[1,2-a]pyridine-2-carboxamide (70 mg, 0.26 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (44 mg, 0.26 mmol) as raw materials.

[0188] 1 H NMR (400 MHz, DMSO-d6) 8.15 (dd, J = 6.8, 1.2 Hz, 1H), 7.52 (d, J = 4.8 Hz, 1H), 7.43 (td, J = 8.4, 7.0 Hz, 1H), 6.98 (d, J = 8.5 Hz, 1H), 6.91 (ddd, J = 16.9, 10.1, 4.0 Hz, 3H), 6.12 (s, 2H), 3.70 (s, 3H), 2.71 (d, J = 4.8 Hz, 3H). LC-MS: m / z [M+H] + = 315.

[0189] Example 2

[0190] [ka]

[0191] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-ethylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-ethylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (100 mg, 0.39 mmol) and ethylamine hydrochloride (47 mg, 0.59 mmol) as raw materials to obtain the target product (50 mg, 45%), which was a yellowish-green solid.

[0192] Step 2: Using the same procedure as in the synthesis example of compound vii, the target product (25 mg, 44%) was obtained from 3-amino-8-bromo-N-ethylimidazo[1,2-a]pyridine-2-carboxamide (50 mg, 0.17 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (30 mg, 0.17 mmol) as raw materials.

[0193] 1 H NMR (400 MHz, DMSO-d6) 8.19 (d, J = 6.8 Hz, 1H), 8.07 (s, 1H), 7.63 (d, J = 7.0 Hz, 1H), 7.48 (dd, J = 15.2, 8.4 Hz, 1H), 7.21 (t, J = 6.9 Hz, 1H), 6.88 (dd, J = 15.0, 8.6 Hz, 2H), 6.18 (s, 2H), 3.83 (s, 3H), 3.44 - 3.27 (m, 2H), 1.19 (t, J = 7.3 Hz, 3H). LC-MS: m / z [M+H] + = 329.

[0194] Example 3

[0195] [ka]

[0196] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure is an example of the synthesis of compound vii.

[0197] Example 4

[0198] [ka]

[0199] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-isopropylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-isopropylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (100 mg, 0.39 mmol) and isopropylamine (35 mg, 0.59 mmol) as raw materials to obtain the target product (30 mg, 26%), which was a yellowish-green solid.

[0200] Step 2: Using the same procedure as in the synthesis example of compound vii, the target product (11 mg, 27%) was obtained from 3-amino-8-bromo-N-isopropylimidazo[1,2-a]pyridine-2-carboxamide (30 mg, 0.117 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (20 mg, 0.117 mmol) as raw materials.

[0201] 1 H NMR (400 MHz, DMSO-d6) 8.16 (d, J = 6.8 Hz, 1H), 7.44 (dd, J = 15.3, 8.3 Hz, 1H), 7.17 (d, J = 8.4 Hz, 1H), 7.09 - 6.78 (m, 4H), 6.15 (s, 2H), 4.08 (dd, J = 14.8, 6.7 Hz, 1H), 3.71 (s, 3H), 1.12 (dd, J = 6.5, 4.3 Hz, 6H). LC-MS: m / z [M+H] + = 343.

[0202] Example 5

[0203] [ka]

[0204] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-cyclopropylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-cyclopropylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (100 mg, 0.39 mmol) and cyclopropylamine (35 mg, 0.59 mmol) as raw materials to obtain the target product (65 mg, 56%), which was a yellowish-green solid. LC-MS: m / z [M+H] + = 295.

[0205] Step 2: Using the same procedure as in the synthesis example of compound vii, the target product (30 mg, 40%) was obtained from 3-amino-8-bromo-N-cyclopropylimidazo[1,2-a]pyridine-2-carboxamide (65 mg, 0.22 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (37 mg, 0.22 mmol) as raw materials.

[0206] 1 H NMR (400 MHz, DMSO-d6) 8.15 (d, J = 6.6 Hz, 1H), 7.51 (d, J = 4.3 Hz, 1H), 7.42 (dd, J =15.3, 8.3 Hz, 1H), 6.97 (d, J = 8.4 Hz, 1H), 6.94 - 6.85 (m, 3H), 6.17 (s, 2H), 3.69 (s, 3H), 2.84 - 2.71 (m, 1H), 0.63 - 0.52 (m, 4H). LC-MS: m / z [M+H] + = 341.

[0207] Example 6

[0208] [ka]

[0209] 3-amino-N-(cyclopropylmethyl)-8-(2-fluoro-6-methoxyphenyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-(cyclopropylmethyl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (route 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (100 mg, 0.39 mmol) and cyclopropylamine (42 mg, 0.59 mmol) as raw materials to obtain the target product (100 mg, crude product), which was a yellowish-green solid.

[0210] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-(cyclopropylmethyl)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (81 mg, 0.48 mmol) were used as raw materials to obtain the target product (34 mg, 30%), which was a yellow solid.

[0211] 1 H NMR (400 MHz, DMSO-d6) 8.16 (d, J = 6.85 Hz, 2 H) 7.63 (t, J = 5.87 Hz, 2 H) 7.44 (d, J = 7.34 Hz, 2 H) 6.84 - 7.05 (m, 6 H) 6.17 (s, 2 H) 3.70 (s,4 H) 3.06 (t, J = 6.60 Hz, 3 H) 1.00 (br. s., 1 H) 0.33 - 0.38 (m, 2 H) 0.19 (d, J = 4.40 Hz, 2 H). LC-MS: m / z [M+1] + = 355.

[0212] Example 7

[0213] [ka]

[0214] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-cyclobutylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-cyclobutylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (100 mg, 0.39 mmol) and cyclobutylamine (42 mg, 0.59 mmol) as raw materials to obtain the target product (25 mg, 20%), which was a yellowish-green solid.

[0215] Step 2: Using the same procedure as in the synthesis example of compound vii, the target product (6 mg, 21%) was obtained from 3-amino-8-bromo-N-cyclobutylimidazo[1,2-a]pyridine-2-carboxamide (25 mg, 0.08 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (14 mg, 0.08 mmol) as raw materials.

[0216] 1 H NMR (400 MHz, DMSO-d6) 8.15 (d, J = 5.8 Hz, 1H), 7.66 (d, J = 8.5 Hz, 1H), 7.44 (dd, J = 15.3, 8.3 Hz, 1H), 6.99 (d, J = 8.4 Hz, 1H), 6.96 - 6.85 (m, 3H), 6.16 (s, 2H), 4.40 (dd, J = 16.7, 8.4 Hz, 1H), 3.71 (s, 3H), 2.15-2.09 (m, 2H), 1.62-1.57 (m, 2H), 1.15 (dd, J = 13.5, 4.4 Hz, 2H). LC-MS: m / z [M+H] + = 355.

[0217] Example 8

[0218] [ka]

[0219] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-(3-methylcyclobutyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-(3-methylcyclobutyl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (100 mg, 0.39 mmol) and 3-methylcyclobutan-1-amine (50 mg, 0.59 mmol) as raw materials to obtain the target product (100 mg, crude product), which was a yellowish-green solid.

[0220] Step 2: Using the same procedure as in the synthesis example of compound vii, the target product (10 mg, 19%) was obtained using 3-amino-8-bromo-N-(3-methylcyclobutyl)imidazo[1,2-a]pyridine-2-carboxamide (50 mg, 0.14 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (24 mg, 0.14 mmol) as starting materials.

[0221] 1H NMR (400 MHz, DMSO-d6) 8.15 (d, J = 6.0 Hz, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.44 (dd, J = 15.4, 8.3 Hz, 1H), 6.99 (d, J = 8.4 Hz, 1H), 6.96 - 6.84 (m, 3H), 6.15 (s, 2H), 4.61 - 4.13 (m, 1H), 3.73 (d, J = 15.9 Hz, 3H), 2.34 - 2.20 (m, 2H), 1.94 (dd, J = 15.1, 8.3 Hz, 1H), 1.86 - 1.65 (m, 2H), 1.06 (d, J = 6.5 Hz, 3H). LC-MS: m / z [M+H] + = 369.

[0222] Example 9

[0223] [ka]

[0224] 3-amino-N-(3,3-difluorocyclobutyl)-8-(2-fluoro-6-methoxyphenyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-(3,3-difluorocyclobutyl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as that for the synthesis of intermediate vi (routine 1, step 2), and the target product (100 mg, crude product) was obtained using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (100 mg, 0.39 mmol) and 3,3-difluorocyclobutan-1-amine (84 mg, 0.78 mmol) as raw materials.

[0225] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-(3,3-difluorocyclobutyl)imidazo[1,2-a]pyridine-2-carboxamide (93 mg, 0.27 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (69 mg, 0.41 mmol) were used as raw materials to obtain the target product (31 mg, 29%), which was a yellow solid.

[0226] 1 H NMR (400 MHz, DMSO-d6) 8.17 (d, J = 5.87 Hz, 2H) 7.35 - 7.53 (m, 1H) 6.80 - 7.02 (m, 4H) 6.25 (br. s., 2H) 4.28 (br. s., 1H) 3.70 (s, 3H)2.79 (br. s., 4H). LC-MS: m / z [M+1] + = 391.

[0227] Example 10

[0228] [ka]

[0229] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-(1-methylazetidine-3-yl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-(3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxamide)azetidine-1-carboxylate tert-butyl The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (100 mg, 0.39 mmol) and tert-butyl 3-aminoazetidine-1-carboxylic acid (100 mg, 0.58 mmol) as raw materials to obtain the crude product (70 mg, 43%). LC-MS: m / z [M+H] + = 410.

[0230] Step 2: 3-amino-N-(azetidine-3-yl)-8-bromoimidazo[1,2-a]pyridine-2-carboxamide 3-(3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxamide)azetidine-1-carboxylate tert-butyl (70 mg, 0.17 mmol) was dissolved in dichloromethane (3 mL), trifluoroacetic acid (1 mL) was added, and the mixture was stirred for 16 hours and concentrated to obtain the target product, which was a yellow, oily crude product (70 mg, 100%). LC-MS: m / z [M+H] + = 310.

[0231] Step 3: 3-amino-8-bromo-N-(1-methylazetidine-3-yl)imidazo[1,2-a]pyridine-2-carboxamide At 25°C, 3-amino-N-(azetidine-3-yl)-8-bromoimidazo[1,2-a]pyridine-2-carboxamide (40 mg, 0.12 mmol) was dissolved in methanol (10 mL). Formaldehyde aqueous solution (30%, 20 mg) and NaCNBH3 (20 mg, 0.3 mmol) were added sequentially, and the mixture was stirred at 25°C for 2 hours. The reaction solution was added dropwise to water (20 mL), extracted with ethyl acetate (30 mL x 3), concentrated, and purified by column chromatography to obtain the target product (35 mg, 55%). LC-MS: m / z [M+H] + = 324.

[0232] Step 4: Using the same procedure as in the synthesis example of compound vii, the target product (7 mg, 17%) was obtained from 3-amino-8-bromo-N-(1-methylazetidine-3-yl)imidazo[1,2-a]pyridine-2-carboxamide (35 mg, 0.11 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (20 mg, 0.12 mmol) as raw materials.

[0233] 1H NMR (400 MHz, DMSO-d6) 8.23 ​​(d, J = 6.7 Hz, 1H), 7.95 (d, J = 7.7 Hz, 1H), 7.51 (dd, J = 15.4, 8.3 Hz, 1H), 7.06 (d, J = 8.5 Hz, 1H), 6.97 LC-MS: m / z [M+H] + = 370.

[0234] Example 11

[0235] [ka]

[0236] 3-amino-N-(bicyclo[1.1.1]pentan-1-yl)-8-(2-fluoro-6-methoxyphenyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-N-(bicyclo[1,1,1]pentan-1-yl)-8-bromoimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as that for the synthesis of intermediate vi (routine 1, step 2), and the target product (200 mg, crude product) was obtained using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (150 mg, 0.59 mmol) and 1-bicyclo[1.1.1]pentylamine hydrochloride (100 mg, 1.18 mmol) as raw materials.

[0237] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-N-(bicyclo[1.1.1]pentan-1-yl)-8-bromoimidazo[1,2-a]pyridine-2-carboxamide (200 mg, 0.62 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (110 mg, 0.62 mmol) were used as raw materials to obtain the target product (173 mg, 76%), which was a yellow solid.

[0238] 1 H NMR (400 MHz, DMSO-d6) 8.15 (d, J = 6.36 Hz, 1H) 7.88 (s, 1H) 7.38 - 7.48 (m, 1H) 6.98 (d, J = 8.31 Hz, 1H) 6.82 - 6.95 (m, 3H) 6.21 (s, 2H)3.70 (s, 3H) 2.04 (s, 6H) 1.88 (s, 1H).LC-MS: m / z [M+1] + = 367.

[0239] Example 12

[0240] [ka]

[0241] 3-amino-N-cyclopentyl-8-(2-fluoro-6-methoxyphenyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-cyclopentylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as that for the synthesis of intermediate vi (routine 1, step 2), and the target product (200 mg, crude product) was obtained using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (150 mg, 0.59 mmol) and cyclopentylamine (100 mg, 1.18 mmol) as raw materials.

[0242] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-cyclopentylimidazo[1,2-a]pyridine-2-carboxamide (200 mg, 0.62 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (210 mg, 1.24 mmol) were used as raw materials to obtain the target product (203 mg, 89%), which was a yellow solid.

[0243] 1 H NMR (400 MHz, DMSO-d6) 8.15 (d, J = 6.85 Hz, 1H) 7.39 - 7.50 (m, 1H) 7.25 - 7.35 (m, 1H) 6.99 (d, J =8.31 ​​Hz, 1H) 6.84 - 6.96 (m, 3H) 6.16(s, 2H) 4.08 - 4.26 (m, 1H) 3.70 (s, 3H) 1.74 - 1.90 (m, 2H) 1.62 (br. s., 2H) 1.48 (br. s., 4H). LC-MS: m / z [M+1] + = 369.

[0244] Example 13

[0245] [ka]

[0246] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-phenylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-phenylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), and the target product was obtained using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid and aniline as starting materials.

[0247] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.30 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) were used as raw materials to obtain the target product (92 mg, 81%), which was a yellow solid.

[0248] 1 HNMR (400MHz, DMSO-d6) 9.40 (s, 1H), 8.23 ​​(d, J = 6.8 Hz, 1H), 7.76 (d, J = 7.8 Hz, 2H), 7.57 - 7.39 (m, 1H), 7.28 (t, J = 7.8 Hz, 2H), 7.06 - 6.98 (m, 3H), 6.97 - 6.90 (m, 2H), 6.41 (s, 2H), 3.73 (s, 3H). LC-MS: m / z [M+H] + = 377.

[0249] Example 14

[0250] [ka]

[0251] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-(pyridine-2-yl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-(pyridine-2-yl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as that for the synthesis of intermediate vi (routine 1, step 2), and the target product was obtained using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid and pyridine-2-amine as starting materials.

[0252] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-(pyridine-2-yl)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.30 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) were used as raw materials to obtain the target product (50 mg, 44%), which was a yellow solid.

[0253] 1 HNMR (400MHz, DMSO-d6) 9.13 (s, 1H), 8.33 - 8.17 (m, 3H), 7.82 (t, J = 7.6 Hz, 1H), 7.49 (q, J = 7.8 Hz, 1H), 7.16 - 7.02 (m, 3H), 7.00 - 6.92 (m, 2H), 6.50 (s, 2H), 3.73 (s, 3H). LC-MS: m / z [M+H] + = 378.

[0254] Example 15

[0255] [ka]

[0256] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-(1-methyl-1H-pyrazole-4-yl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-(1-methyl-1H-pyrazole-4-yl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), and the target product was obtained using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid and 1-methyl-1H-pyrazole-4-amino as starting materials.

[0257] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-(1-methyl-1H-pyrazole-4-yl)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.30 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) were used as raw materials to obtain the target product (78 mg, 69%), which was a yellow solid.

[0258] 1 HNMR (400MHz, DMSO-d6) 9.72 (s, 1H), 8.20 (d, J = 6.4 Hz, 1H), 7.96 (s, 1H), 7.64 (s, 1H), 7.45 (q, J = 7.8 Hz, 1H), 7.04 - 6.83 (m, 4H), 6.31 (br. s., 2H), 3.78 (s, 3H), 3.71 (s, 3H). LC-MS: m / z [M+H] + = 381.

[0259] Example 16

[0260] [ka]

[0261] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-(5-methylisoxazole-3-yl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-(5-methylisoxazole-3-yl)imidazo[1,2-a]pyridine-2-carboxamide 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (110 mg, 0.40 mmol) was dissolved in pyridine (2 mL), and 5-methylisoxazole-3-amine (79 mg, 0.80 mmol) and N,N-dimethylpyridine-4-amine (49 mg, 0.40 mmol) were added. The mixture was stirred for 10 minutes, then thionyl chloride (95 mg, 0.80 mmol) was added dropwise, and the mixture was stirred at room temperature for 16 hours. The reaction solution was concentrated, water (20 mL) was added, and the mixture was extracted with ethyl acetate (50 mL x 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography (dichloromethane:methanol = 10:1) to obtain the product (71 mg, 52.5%). LC-MS: m / z [M+H] + = 336.

[0262] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-(5-methylisoxazole-3-yl)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.30 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) were used as raw materials to obtain the target product (8 mg, 7%), which was a gray solid.

[0263] 1 HNMR (400MHz, DMSO-d6) 9.56 (br. s., 1 H), 8.26 (d, J = 6.8 Hz, 1 H), 7.47 (q, J = 7.7 Hz, 1 H), 7.07 - 6.98 (m, 2 H), 6.98 - 6.90 (m, 2 H), 6.70 (s, 1 H), 6.51 (br. s., 2 H), 3.72 (s, 3 H), 2.39 (s, 3 H). LC-MS: m / z [M+H] + = 382.

[0264] Example 17

[0265] [ka]

[0266] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-(5-methylthiazole-2-yl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-(5-methylthiazole-2-yl)imidazo[1,2-a]pyridine-2-carboxamide 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (150 mg, 0.59 mmol) was dissolved in DMF (1 mL), and 5-methylthiazole-2-amine (135 mg, 1.18 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.: 25952-53-8, 170 mg, 0.89 mmol), and N,N-dimethylpyridine-4-amine (144 mg, 1.18 mmol) were added sequentially. The reaction solution was stirred at 50°C for 6 hours. Water (20 mL) was added to the reaction solution to quench it, the aqueous phase was extracted with ethyl acetate (50 mL x 3), the organic phase was combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography (petroleum ether:ethyl acetate = 1:1) to obtain the product (91 mg, 44%). LC-MS: m / z [M+H] + = 352.

[0267] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-(5-methylthiazole-2-yl)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) were used as raw materials to obtain the target product (18 mg, 16%), which was a yellow solid.

[0268] 1HNMR (400MHz, DMSO-d6) 10.35 (br. s., 1 H), 8.27 (d, J = 6.8 Hz, 1 H), 7.47 (d, J = 7.3 Hz, 1 H), 7.11 (s, 1 H), 7.02 (d, J = 8.3 Hz, 2 H), 7.05 (d, J = 6.8 Hz, 2 H), 6.97 - 6.90 (m, 2 H), 6.61 (br. s., 2 H), 3.72 (s, 3 H), 2.35 (s, 3 H). LC-MS: m / z [M+H] + =398.

[0269] Example 18

[0270] [ka]

[0271] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-((5-methyl-1,3,4-oxadiazole-2-yl)methyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-((5-methyl-1,3,4-oxadiazole-2-yl)methyl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), and the target product was obtained using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid and (5-methyl-1,3,4-oxadiazole-2-yl)methylamine as starting materials.

[0272] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-((5-methyl-1,3,4-oxadiazole-2-yl)methyl)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.28 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) were used as raw materials to obtain the target product (81 mg, 72%), which was a yellow solid.

[0273] 1 H NMR (400MHz, DMSO-d6) 8.30 - 8.09 (m, 2 H), 7.44 (q, J = 7.8 Hz, 1 H), 7.06 - 6.83 (m, 4 H), 6.24 (s, 2 H), 4.56 (d, J = 5.9 Hz, 2 H), 3.71 (s, 3 H), 2.44 (s, 3 H). LC-MS: m / z [M+H] + = 397.

[0274] Example 19

[0275] [ka]

[0276] 3-amino-N-benzyl-8-(2-fluoro-6-methoxyphenyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-benzylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), and the target product was obtained using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid and benzylamine as starting materials.

[0277] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-benzylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.29 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) were used as raw materials to obtain the target product (48 mg, 43%), which was a yellow solid.

[0278] 1HNMR (400MHz, DMSO-d6) 8.23 ​​- 8.07 (m, 2 H), 7.51 - 7.36 (m, 1 H), 7.28 (d, J = 4.4 Hz, 4 H), 7.23 - 7.17 (m, 1 H), 7.02 - 6.86 (m, 4 H), 6.19 (s, 2 H), 4.39 (d, J = 6.4 Hz, 2 H), 3.70 (s, 3 H). LC-MS: m / z [M+H] + = 391.

[0279] Example 20

[0280] [ka]

[0281] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-(pyridine-2-methyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-(pyridine-2-methyl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as that for the synthesis of intermediate vi (routine 1, step 2), and the target product was obtained using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid and pyridine-2-methylamine as starting materials.

[0282] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-(pyridine-2-methyl)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.30 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) were used as raw materials to obtain the target product (63 mg, 56%), which was a yellow solid.

[0283] 1HNMR (400MHz, DMSO-d6) 8.47 (br. s., 1 H), 8.18 (d, J = 5.9 Hz, 2 H), 7.75 - 7.69 (m, 1 H), 7.44 (q, J = 7.8 Hz, 1 H), 7.34 - 7.16 (m, 2 H), 7.05 - 6.84 (m, 4 H), 6.19 (br. s., 2 H), 4.51 (d, J = 5.4 Hz, 2 H), 3.72 (s, 3 H). LC-MS: m / z [M+H] + = 392.

[0284] Example 21

[0285] [ka]

[0286] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-phenylethylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-phenylethylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (100 mg, 0.39 mmol) and phenylethylamine (71 mg, 0.59 mmol) as raw materials to obtain the target product (100 mg, crude product), which was a yellowish-green solid.

[0287] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-phenylethylimidazo[1,2-a]pyridine-2-carboxamide (0.05 g, 0.14 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (0.029 g, 0.17 mmol) were used as raw materials to obtain the product (20 mg, 35%), which was a yellow solid.

[0288] 1H NMR (400MHz, DMSO-d6) 8.17 (d, J = 6.4 Hz, 1 H), 7.65 (s, 1 H), 7.48 - 7.40 (m, 1 H), 7.26 (d, J = 6.8 Hz, 2 H), 7.19 (d, J = 6.8 Hz, 3 H), 7.02 - 6.88 (m, 4 H), 6.18 (s, 2 H), 3.69 (s, 3 H), 3.42 (d, J = 6.8 Hz, 2 H), 2.78 (t, J = 6.8 Hz, 2 H). LC-MS: m / z [M+1] + = 405.

[0289] Example 22

[0290] [ka]

[0291] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-(2-hydroxyethyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-(2-hydroxyethyl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (route 2, step 1), using ethyl 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylate (100 mg, 0.35 mmol) and ethanolamine (1.1 g, 17.5 mmol) as raw materials to obtain the target product (100 mg), which was a yellow solid.

[0292] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-(2-hydroxyethyl)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.33 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (56 mg, 0.33 mmol) were used as raw materials to obtain the target product (39 mg, 34%), which was a yellow solid.

[0293] 1 H NMR (400 MHz, DMSO-d6) 8.08 - 8.24 (m, 1 H) 7.38 - 7.52 (m, 2 H) 6.82 - 7.03 (m, 4 H) 6.15 (s, 2 H) 5.75 (s, 1 H) 4.64 - 4.77 (m, 1 H) 3.70 (s,3 H) 3.44 (d, J=5.38 Hz, 2 H) 3.28 (d, J=5.87 Hz, 2 H).LC-MS: m / z [M+1] + = 345.

[0294] Example 23

[0295] [ka]

[0296] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-(3-hydroxypropyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-(3-hydroxypropyl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (100 mg, 0.39 mmol) and 3-amino-1-propanol (44 mg, 0.59 mmol) as raw materials to obtain the target product (50 mg, 41%), which was a yellowish-green solid.

[0297] Step 2: Using the same procedure as in the synthesis example of compound vii, the target product (15 mg, 26%) was obtained from 3-amino-8-bromo-N-(3-hydroxypropyl)imidazo[1,2-a]pyridine-2-carboxamide (50 mg, 0.16 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (27 mg, 0.16 mmol) as raw materials.

[0298] 1H NMR (400 MHz, DMSO-d6) 8.16 (d, J = 6.0 Hz, 1H), 7.59 (t, J = 6.1 Hz, 1H), 7.43 (dd, J = 15.3, 8.3 Hz, 1H), 6.99 (d, J = 8.4 Hz, 1H), 6.96 - 6.84 (m, 3H), 6.14 (s, 2H), 4.44 (t, J = 5.4 Hz, 1H), 3.71 (s, 3H), 3.39 (dd, J = 11.9, 6.1 Hz, 2H), 3.27 (dd, J = 13.7, 6.8 Hz, 2H), 1.60 (p, J = 6.5 Hz, 2H). LC-MS: m / z [M+H] + = 359.

[0299] Example 24

[0300] [ka]

[0301] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-(2-methoxyethyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-(2-methoxyethyl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (route 2, step 1), using ethyl 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylate (100 mg, 0.35 mmol) and 2-methoxyethane-1-amine (1.3 g, 17.5 mmol) as raw materials to obtain the target product (100 mg), which was a yellow solid.

[0302] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-(2-methoxyethyl)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (54 mg, 0.32 mmol) were used as raw materials to obtain the target product (52 mg, 45%), which was a yellow solid.

[0303] 1 H NMR (400 MHz, DMSO-d6) 8.16 (d, J=5.87 Hz, 1 H) 7.37 - 7.52 (m, 2 H) 6.84 - 7.04 (m, 4 H) 6.17 (s, 2 H) 3.70 (s, 3 H) 3.38 (s, 4 H) 3.22 (s, 3H).LC-MS: m / z [M+1] + = 359.

[0304] Example 25

[0305] [ka]

[0306] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-(3,3,3-trifluoropropyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-(3,3,3-trifluoropropyl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (100 mg, 0.39 mmol) and 3,3,3-trifluoropropan-1-amine (132 mg, 1.17 mmol) as raw materials to obtain the target product (50 mg, 36%), which was a yellowish-green solid. LC-MS: m / z [M+H] + =351.

[0307] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-(3,3,3-trifluoropropyl)imidazo[1,2-a]pyridine-2-carboxamide (50 mg, 0.14 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (24 mg, 0.14 mmol) were used as raw materials to obtain the target product (9 mg, 16%).

[0308] 1 H NMR (400 MHz, DMSO-d6) 8.17 (d, J = 6.0 Hz, 1H), 7.79 (t, J = 6.1 Hz, 1H), 7.43 (dd, J = 15.4, 8.3 Hz, 1H), 6.99 (d, J = 8.4 Hz, 1H), 6.91 LC-MS: m / z [M+H] + = 397.

[0309] Example 26

[0310] [ka]

[0311] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-butylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-butylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (100 mg, 0.39 mmol) and butylamine (83 mg, 1.13 mmol) as raw materials to obtain the target product (40 mg, 33%), which was a yellowish-green solid. LC-MS: m / z [M+H] + = 313.

[0312] Step 2: Using the same procedure as in the synthesis example of compound vii, the target product (21 mg, 46%) was obtained from 3-amino-8-bromo-N-(3,3,3-trifluoropropyl)imidazo[1,2-a]pyridine-2-carboxamide (40 mg, 0.128 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (24 mg, 0.14 mmol) as starting materials.

[0313] 1 H NMR (400 MHz, DMSO-d6) 8.15 (d, J = 6.9 Hz, 1H), 7.54 (t, J = 5.9 Hz, 1H), 7.43 (dd, J = 15.5, 8.1 Hz, 1H), 6.99 (d, J = 8.4 Hz, 1H), 6.96 - 6.84 (m, 3H), 6.13 (s, 2H), 3.70 (s, 3H), 3.20 (dd, J = 13.6, 6.8 Hz, 2H), 1.43 (dd, J = 14.6, 7.4 Hz, 2H), 1.25 (dd, J = 14.7, 7.3 Hz, 2H), 0.86 (t, J = 7.3 Hz, 3H). LC-MS: m / z [M+H] + = 357.

[0314] Example 27

[0315] [ka]

[0316] 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-(3-fluoropropyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-Fluoro-N-(4-methoxybenzyl)propan-1-amine (4-methoxyphenyl)methylamine (150 mg, 1.1 mmol), potassium carbonate (303 mg, 2.2 mmol), and 1-fluoro-3-iodopropane (247 mg, 1.3 mmol) were sequentially added to N,N-dimethylformamide (5 mL), and the mixture was stirred at 100°C for 16 hours. The mixture was filtered, concentrated, and the target product (100 mg, 46%) was obtained by column chromatography. LC-MS: m / z [M+H] + = 198.

[0317] Step 2: 3-amino-8-bromo-N-(3-fluoropropyl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (130 mg, 0.5 mmol) and 3-fluoro-N-(4-methoxybenzyl)propan-1-amine (100 mg, 0.5 mmol) as raw materials to obtain the target product (70 mg, 32%), which was a pale green solid. LC-MS: m / z [M+H] + = 437.

[0318] Step 3: 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-(3-fluoropropyl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, the target product (60 mg, 78%) was obtained from 3-amino-8-bromo-N-(3-fluoropropyl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-2-carboxamide (70 mg, 0.16 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (30 mg, 0.17 mmol) as starting materials. LC-MS: m / z [M+H] + = 481.

[0319] Step 4: At 25°C, 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-(3-fluoropropyl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-2-carboxamide (30 mg, 0.06 mmol) was dissolved in dichloromethane (3 mL), and trifluoroacetic acid (1 mL) was added dropwise. The solution was concentrated, and the target product (5 mg, 23%) was obtained by column chromatography.

[0320] 1 H NMR (400 MHz, DMSO-d6) 8.16 (d, J = 6.6 Hz, 1H), 7.70 (t, J = 6.1 Hz, 1H), 7.43 (dd, J = 15.3, 8.3 Hz, 1H), 6.99 (d, J = 8.5 Hz, 1H), 6.91 (dt, J = 13.6, 6.4 Hz, 3H), 6.16 (s, 2H), 4.50 (t, J = 5.9 Hz, 1H), 4.38 (t, J = 5.9 Hz, 1H), 3.70 (s, 3H), 3.29 (d, J = 6.7 Hz, 2H), 1.93 - 1.72 (m, 2H). LC-MS: m / z [M+H] + = 361.

[0321] Example 28

[0322] [ka]

[0323] 3-amino-N-(2-cyanoethyl)-8-(2-fluoro-6-methoxyphenyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-(2-cyanoethyl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (100 mg, 0.39 mmol) and 3-aminopropionitrile (33 mg, 0.47 mmol) as raw materials to obtain the target product (118 mg, 90%), which was a yellow oily substance. LC-MS: m / z [M+H] + = 308.

[0324] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-(2-cyanoethyl)imidazo[1,2-a]pyridine-2-carboxamide (118 mg, 0.38 mmol) and 2-fluoro-6-methoxyphenylboronic acid (73 mg, 0.43 mmol) were used as starting materials to obtain the title product (32 mg, 24%), which was a pale yellow solid (32 mg, yield: 24%).

[0325] 1 HNMR (400 MHz, DMSO-d6) 8.18 (d, J = 6.7 Hz, 1H), 7.90 (t, J = 5.9 Hz, 1H), 7.43 (dd, J = 15.5, 8.1 Hz, 1H), 6.99 (d, J = 8.4 Hz, 1H), 6.97 - 6.86 (m, 3H), 6.21 (s, 2H), 3.71 (s, 3H), 3.45 (dd, J = 12.6, 6.2 Hz, 2H), 2.72 (t, J = 6.5 Hz, 2H). LC-MS: m / z [M+H] + =354.

[0326] Example 29

[0327] [ka]

[0328] 3-amino-N-(cyanomethyl)-8-(2-fluoro-6-methoxyphenyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-(cyanomethyl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (200 mg, 0.78 mmol) and 2-aminoacetonitrile (87.8 mg, 1.56 mmol) as raw materials to obtain the target product (110 mg, 48%). LC-MS: m / z [M+1] = 294.

[0329] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-(cyanomethyl)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (116 mg, 0.68 mmol) were used as raw materials to obtain the target product (25 mg, 21.6%).

[0330] 1 H NMR (400 MHz, DMSO-d6) 9.15 (t, J = 6.0 Hz, 1H), 8.43 (d, J = 7.3 Hz, 1H), 7.83- 7.70 (m, 2H), 6.97 (d, J = 30.2 Hz, 2H), 4.68 (s, 2H), 3.70 (s, 3H), 3.44 (s, 3H), 3.32 (d, J = 6.8 Hz, 2H), 1.70 - 1.54 (m, 2H), 1.00 - 0.86 (m, 3H). LC-MS: m / z [M+1]= 340.

[0331] Example 30

[0332] [ka]

[0333] N-allyl-3-amino-8-(2-fluoro-6-methoxyphenyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: N-allyl-3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (300 mg, 1.17 mmol) and prop-2-en-1-amine (134 mg, 2.34 mmol) as raw materials to obtain the target product (164 mg, 47%), which was a yellow solid. LCMS: m / z [M+H] + =295.

[0334] Step 2: Using the same procedure as in the synthesis example of compound vii, N-allyl-3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxamide (160 mg, 0.54 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (184 mg, 1.08 mmol) were used as raw materials to obtain the target product (16 mg, 8.7%), which was a yellow solid.

[0335] 1 H NMR (400MHz, CD3OD) δ 8.07 (d, J = 6.8 Hz, 1 H), 7.48 - 7.41 (m, 1 H), 7.04 (d, J = 6.8 Hz, 1 H), 6.98 - 6.91 (m, 2 H), 6.85 (t, J = 8.6 Hz, 1 LCMS: m / z [M+H] + = 341.

[0336] Example 31

[0337] [ka]

[0338] N-propargyl-3-amino-8-(2-fluoro-6-methoxyphenyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: N-propargyl-3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (300 mg, 1.17 mmol) and prop-2-in-1-amine (134 mg, 2.34 mmol) as raw materials to obtain the target product (129 mg, 38%), which was a yellow solid. LCMS: m / z [M+H] + = 293.

[0339] Step 2: Using the same procedure as in the synthesis example of compound vii, the target product (36 mg, 24%) was obtained from N-propargyl-3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxamide (129 mg, 0.44 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (184 mg, 1.08 mmol) as raw materials.

[0340] 1 H NMR (400 MHz, CD3OD) δ 8.07 (d, J = 6.8 Hz, 1 H), 7.45 (q, J = 7.8 Hz, 1 H), 7.04 (d, J = 6.8 Hz, 1 H), 6.98 - 6.90 (m, 2 H), 6.86 (t, J = 8.6 Hz, 1 H), 4.10 (s, 2 H), 3.75 (s, 3 H), 2.57 (br. s, 1 H). LCMS: m / z [M+H] + = 339.

[0341] Example 32

[0342] [ka]

[0343] 3-amino-8-(2,3-difluoro-6-methoxyphenyl)-N-(3-methylcyclobutyl)imidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-(3-methylcyclobutyl)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.30 mmol) and (2,3-difluoro-6-methoxyphenyl)boronic acid (85 mg, 0.45 mmol) were used as raw materials to obtain the target product (16 mg, 14%), which was a yellow solid.

[0344] 1 H NMR (400 MHz, DMSO-d6) 8.18 (d, J=6.85 Hz, 1 H) 7.68 (d, J=8.80 Hz, 1 H) 7.49 (d, J=9.78 Hz, 1 H) 6.87 - 7.03 (m, 1 H) 6.20 (s, 2 H) 4.12 -4.30 (m, 1 H) 3.69 (s, 3 H) 2.27 (d, J=6.36 Hz, 2 H) 1.73 (d, J=9.29 Hz, 3 H) 1.01 (d, J=6.36 Hz, 3 H). LC-MS: m / z [M+1] + = 387.

[0345] Example 33

[0346] [ka]

[0347] 3-amino-8-(2-methoxy-5-methylphenyl)-N-(3-methylcyclobutyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-N-(3-methylcyclobutyl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (400 mg, 1.56 mmol) and 3-methylcyclobutan-1-amine (200 mg, 2.36 mmol) as raw materials to obtain the target product (400 mg, crude product), which was a yellowish-green solid.

[0348] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-(3-methylcyclobutyl)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.30 mmol) and (2-methoxy-5-methylphenyl)boronic acid (75 mg, 0.45 mmol) were used as raw materials to obtain the target product (11 mg, 10%), which was a yellow solid.

[0349] 1 H NMR (400 MHz, DMSO-d6) 8.09 (d, J=6.85 Hz, 1 H) 7.47 - 7.61 (m, 1 H) 7.23 (br. s., 3 H) 7.03 (d, J=7.83 Hz, 1 H) 6.93 (br. s., 2 H) 6.85 (s, 2H) 6.13 (s, 2 H) 4.16 - 4.30 (m, 1 H) 3.67 (s, 4 H) 2.29 (s, 5 H) 1.62 - 2.01 (m, 3 H) 1.01 (d, J=6.36 Hz, 3 H).LC-MS: m / z [M+1] + = 365.

[0350] Example 34

[0351] [ka]

[0352] 3-amino-8-(5-cyano-2-methoxyphenyl)-N-(3-methylcyclobutyl)imidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-(3-methylcyclobutyl)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.30 mmol) and (5-cyano-2-methoxyphenyl)boronic acid (80 mg, 0.45 mmol) were used as raw materials to obtain the target product (28 mg, 25%), which was a yellow solid.

[0353] 1 H NMR (400 MHz, DMSO-d6) 8.15 (d, J=6.85 Hz, 2 H) 7.85 - 7.93 (m, 3 H) 7.70 (d, J=8.31 ​​Hz, 1 H) 7.32 (d, J=9.29 Hz, 2 H) 7.04 (d, J=6.85 Hz, 2H)6.89 (t, J=6.85 Hz, 2 H) 6.18 (s, 2 H) 4.12 - 4.29 (m, 1 H) 3.81 (s, 3 H) 2.15 - 2.33 (m, 2 H) 1.66 (d, J=10.27 Hz, 3 H) 1.00 (d, J=6.36 Hz, 2 H).LC-MS: m / z [M+1] + = 376.

[0354] Example 35 (Area B)

[0355] [ka]

[0356] 3-amino-8-(3-cyanophenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and 3-cyanophenylboronic acid (50 mg, 0.34 mmol) were used as raw materials to obtain the target product (105 mg, 97%), which was a yellow solid.

[0357] 1H NMR (400 MHz, CHLOROFORM) 8.40 (s, 1 H) 8.21 (d, J=7.83 Hz, 1 H) 7.79 (d, J=6.85 Hz, 1 H) 7.72 (d, J=7.83 Hz, 1 H) 7.58 - 7.65 (m, 1 H) 7.25 (d, LC-MS: m / z [M+1] + = 320.

[0358] Example 36

[0359] [ka]

[0360] 3-amino-8-(3-(cyanomethyl)phenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (50 mg, 0.17 mmol) and (3-(cyanomethyl)phenyl)boronic acid (41 mg, 0.26 mmol) were used as raw materials to obtain the target product (30 mg, 53%), which was a yellow solid.

[0361] 1H NMR (400 MHz, DMSO-d6) 8.40 (s, 1 H) 8.16 (d, J=6.85 Hz, 1 H) 8.04 (d, J=7.83 Hz, 1 H) 7.70 (s, 1 H) 7.52 (t, J=7.83 Hz, 1 H) 7.39 (d, J=6.85Hz, 2 H) 6.96 (t, J=6.85 Hz, 1 H) 6.17 (s, 2 H) 4.16 (s, 2 H) 3.17 - 3.28 (m, 2 H) 1.48 - 1.58 (m, 2 H) 0.88 (t, J=7.34 Hz, 3 H). LC-MS: m / z [M+1] + = 334.

[0362] Example 37

[0363] [ka]

[0364] 3-amino-8-(3-(2-cyanoethyl)phenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (200 mg, 0.67 mmol) and 3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propionitrile (181 mg, 0.68 mmol) were used as raw materials to obtain the target product (4 mg, 3%), which was a yellow solid.

[0365] 1H NMR (400 MHz, DMSO-d6)8.10 - 8.16 (m, 1 H) 8.01 - 8.07 (m, 1 H) 7.90 - 7.97 (m, 1 H) 7.75 - 7.83 (m, 1 H) 7.42 - 7.49 (m, 1 H) 7.25 - 7.37(m, 2 H) 6.90 - 6.98 (m, 1 H) 6.06 - 6.21 (m, 2 H) 3.16 - 3.25 (m, 2 H) 2.94 - 3.03 (m, 2 H) 2.83 - 2.91 (m, 2 H) 1.46 - 1.57 (m, 2 H) 0.78 - 0.92 (m, 3 H).LC-MS: m / z [M+1] + = 348.

[0366] Example 38

[0367] [ka]

[0368] (E)-3-amino-8-(3-(1-(methoxyimino)ethyl)phenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 8-(3-acetylphenyl)-3-amino-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 88%) was obtained from 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 88%) using 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 88%) as raw materials, and (3-acetylphenyl)boronic acid (84 mg, 0.51 mmol). The intermediate, methoxyamine hydrochloride (50 mg, 0.6 mmol) and aqueous sodium hydroxide solution (2N, 0.5 mL), were sequentially added to methanol (2 mL), stirred at room temperature for 2 hours, water (20 mL) was added, and the mixture was extracted with dichloromethane (30 mL x 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified on a preparative plate (petroleum ether:ethyl acetate = 1:1) to obtain the target product (79 mg, 73%), which was a white solid.

[0369] 1 H NMR (400 MHz, DMSO-d6) 8.40 (s, 1 H) 8.16 (d, J=6.85 Hz, 1 H) 8.04 (d, J=7.83 Hz, 1 H) 7.70 (s, 1 H) 7.52 (t, J=7.83 Hz, 1 H) 7.39 (d, J=6.85Hz, 2 H) 6.96 (t, J=6.85 Hz, 1 H) 6.17 (s, 2 H) 4.16 (s, 2 H) 3.17 - 3.28 (m, 2 H) 1.48 - 1.58 (m, 2 H) 0.88 (t, J=7.34 Hz, 3 H). LC-MS: m / z [M+1] + = 366.

[0370] Example 39

[0371] [ka]

[0372] 3-amino-8-(3-(7-ethyl-7H-imidazo[4,5-c]pyridazin-4-yl)phenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 4-(3-chlorophenyl)-7-ethyl-7H-imidazo[4,5-c]pyridazine 4-Chloro-7-ethyl-7-imidazopyridazine (100 mg, 0.55 mmol), 3-chlorophenylboronic acid (94 mg, 0.6 mmol), cesium carbonate (536 g, 1.65 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II) dichloride (CAS No.: 95408-45-0, 35 mg, 0.055 mmol) were sequentially added to a mixture of dioxane and water (5 mL / 0.5 mL). The mixture was stirred at 90°C for 1 hour under the protection of nitrogen gas, and purified by column chromatography (petroleum ether:ethyl acetate = 2:1) to obtain the title compound (120 mg, brown solid) in 85% yield. LC-MS: m / z [M+H] + =259.

[0373] Step 2: 7-Ethyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-7H-imidazo[4,5-c]pyridazine Under the protection of nitrogen gas, 4-(3-chlorophenyl)-7-ethyl-7H-imidazo[4,5-c]pyridazine (120 mg, 0.47 mmol), bis(pinacolate)diborone (143 mg, 0.56 mmol), potassium acetate (137 mg, 1.4 mmol), X-Phos (41 mg, 0.2 mmol), and Pd2(dba)3 (21 mg, 0.05 mmol) were sequentially added to dioxane (5 mL), and the mixture was stirred at 100 °C for 16 hours. Column chromatography (petroleum ether:ethyl acetate = 1:1) yielded the title product (120 mg, brown solid) with a yield of 72%. LC-MS: m / z [M+H] + =351.

[0374] Step 3: The procedure was the same as in the synthesis example of compound vii, using 7-ethyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-7H-imidazo[4,5-c]pyridazine (63 mg, 0.18 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (50 mg, 0.17 mmol) as raw materials to obtain the title product (30 mg, yield: 40%), which was a yellow solid.

[0375] 1HNMR(400 MHz, DMSO-d6) 9.59 (s, 1H), 9.05 (s, 1H), 8.87 (s, 1H), 8.40 (d, J = 7.9 Hz, 1H), 8.33 (d, J = 7.9 Hz, 1H), 8.20 (d, J = 6.8 Hz, 1H), 7.79 - 7.67 (m, 2H), 7.45 (d, J = 6.8 Hz, 1H), 7.00 (t, J = 6.9 Hz, 1H), 6.18 (s, 2H), 4.53 (q, J = 7.3 Hz, 2H), 3.25 (dd, J = 13.8, 6.5 Hz, 2H), 1.57 (t, J = LC-MS: m / z [M+H] + = 441.

[0376] Example 40

[0377] [ka]

[0378] 3-amino-8-(3-(propa-1-in-1-yl)phenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (3-(prop-1-in-1-yl)phenyl)boronic acid (109 mg, 0.68 mmol) were used as raw materials to obtain the target product (75 mg, 67%), which was a yellow solid.

[0379] 1HNMR (400MHz, DMSO-d6) 8.15-8.11 (m, 2 H), 7.94 (s, 1 H), 7.72 (br. s., 1 H), 7.49 - 7.38 (m, 2 H), 7.30 (d, J = 6.8 Hz, 1 H), 6.92 (t, J = LC-MS: m / z [M+H] + =333.

[0380] Example 41

[0381] [ka]

[0382] 3-amino-8-(3-(2-oxoxazolidine-3-yl)phenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-(3-bromophenyl)oxazolidine-2-one 1-Bromo-3-iodobenzene (500 mg, 1.77 mmol), oxazolidine-2-one (427 mg, 5.32 mmol), cyclohexanediamine (16 mg, 0.14 mmol), and potassium carbonate (734 mg, 5.32 mmol) were sequentially added to dioxane (10 mL). The mixture was stirred at 110 °C for 5 hours. The reaction solution was poured into water (50 mL), extracted with ethyl acetate (50 ml x 3), concentrated, and the target product (320 mg, 68%) was obtained by column chromatography. LC-MS: m / z [M+H] + = 242.

[0383] Step 2: 3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxybenzofuran-2-yl)phenyl)oxazolidine-2-one 3-(3-bromophenyl)oxazolidine-2-one (200 mg, 0.83 mmol), bis(pinacolate)diborone (420 mg, 1.65 mmol), potassium acetate (243 mg, 2.48 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II) dichloride (30 mg, 0.04 mmol) were sequentially added to dioxane (5 ml). The mixture was stirred at 100°C for 2 hours under the protection of argon gas. The mixture was concentrated, and a pale yellow powder (80 mg, 33.5%) was obtained by column chromatography. LC-MS: m / z [M+1] = 290.

[0384] Step 3: The procedure was the same as in the synthesis example of compound vii, using 3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxybenzofuran-2-yl)phenyl)oxazolidine-2-one (80 mg, 0.27 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (82 mg, 0.27 mmol) as raw materials to obtain the target product (20 mg, yield: 19.5%), which was a yellow powder.

[0385] 1 H NMR (400 MHz, DMSO-d6) 8.58 (s, 1H), 8.20 (d, J = 6.9 Hz, 1H), 7.87 - 7.76 (m, 2H), 7.63 (dd, J = 8.1, 1.7 Hz, 1H), 7.52 (t, J = 8.0 Hz, 1H), 7.43 (d, J = 6.9 Hz, 1H), 7.00 (s, 1H), 4.47 (dd, J = 8.9, 7.0 Hz, 2H), 4.24 - 4.10 (m, 2H), 3.25 (dd, J = 13.7, 6.5 Hz, 2H), 1.55 (dd ,J = 14.4, 7.3 Hz, 2H), 0.89 (t, J = 7.4 Hz, 3H). LC-MS: m / z [M+1]= 380.

[0386] Example 42

[0387] [ka]

[0388] 3-amino-8-(1-(5-methyl-1,3,4-oxadiazole-2-yl)-1,2,5,6-tetrahydropyridine-3-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 5-(3-amino-2-(propylcarbamoyl)imidazo[1,2-a]pyridine-8-yl)-3,6-dihydropyridine-1(2H)-carboxylate tert-butyl The procedure was the same as that for the synthesis of compound vii. Using 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate tert-butyl (300 mg, 0.97 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (288 mg, 0.97 mmol) as starting materials, the target product (200 mg, yield: 52%) was obtained. LC-MS: m / z [M+H] + = 400.

[0389] Step 2: 3-amino-N-propyl-8-(1,2,5,6-tetrahydropyridine-3-yl)imidazo[1,2-a]pyridine-2-carboxamide At 25°C, 200 mg (0.5 mmol) of 5-(3-amino-2-(propylcarbamoyl)imidazo[1,2-a]pyridine-8-yl)-3,6-dihydropyridine-1(2H)-carboxylate tert-butyl was dissolved in 3 mL of dichloromethane, and 1 mL of trifluoroacetic acid was added dropwise. The mixture was stirred for 16 hours. The solution was concentrated to obtain the target product (120 mg, crude product), which was a brown oily substance. LC-MS: m / z [M+H] + =300.

[0390] Step 3: 3-amino-N-propyl-8-(1,2,5,6-tetrahydropyridine-3-yl)imidazo[1,2-a]pyridine-2-carboxamide (50 mg, 0.16 mmol), 2-bromo-5-methyl-1,3,4-oxadiazole (40 mg, 0.25 mmol), and triethylamine (50 mg, 0.48 mmol) were sequentially added to anhydrous ethanol (1.5 ml). The mixture was reacted at 130°C using microwaves for 2 hours. The title compound (25 mg, 41%) was obtained by column chromatography.

[0391] 1 H NMR (400 MHz, DMSO-d6) 8.11 (d, J = 6.9 Hz, 1H), 7.90 (t, J = 5.8 Hz, 1H), 7.27 (s, 1H), 7.09 (d, J = 7.0 Hz, 1H), 6.89 (t, J = 7.0 Hz, 1H), 5.56 (s, 2H), 4.49 (d, J = 1.7 Hz, 2H), 3.63 (t, J = 5.8 Hz, 2H), 3.24 (dd, J = 13.9, 6.5 Hz, 2H), 2.49 - 2.45 (m, 2H), 2.35 (s, 3H), 1.54 (dt, J = 14.5, 7.3 Hz, 2H), 0.89 (t, J = 7.4 Hz, 3H). LC-MS: m / z [M+H] + =382.

[0392] Example 43

[0393] [ka]

[0394] 3-amino-8-(3-(5-methyl-1,3,4-oxadiazole-2-yl)phenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-(3-amino-2-(propylcarbamoyl)imidazo[1,2-a]pyridine-8-yl)methyl benzoate Step 2: Using the same procedure as in the synthesis example of compound vii, (3-(methoxycarbonyl)phenyl)boronic acid (100 mg, 0.56 mmol) and 33-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (165 mg, 0.56 mmol) were used as raw materials to obtain a pale green solid (120 mg, 61%). LC-MS: m / z [M+H] + =353.

[0395] Step 2: 3-(3-amino-2-(propylcarbamoyl)imidazo[1,2-a]pyridine-8-yl)benzoic acid 3-(3-amino-2-(propylcarbamoyl)imidazo[1,2-a]pyridine-8-yl)methyl benzoate (120 mg, 0.34 mmol) was dispersed in tetrahydrofuran / water (2 mL / 2 mL), lithium hydroxide monohydrate (54 mg, 1.36 mmol) was added, and the mixture was heated to 45°C and stirred for 16 hours to obtain a grayish-white solid (100 mg, 87%). LC-MS: m / z [M+H] + = 339.

[0396] Step 3: 8-(3-(2-acetylhydrazine-1-carbonyl)phenyl)-3-amino-N-propylimidazo[1,2-a]pyridine-2-carboxamide 3-(3-amino-2-(propylcarbamoyl)imidazo[1,2-a]pyridine-8-yl)benzoic acid (80 mg, 0.23 mmol), HATU (131 mg, 0.345 mmol), acetohydrazide (25.5 mg, 0.345 mmol), and triethylamine (100 mg, 1 mmol) were sequentially added to N,N-dimethylformamide (5 mL). The mixture was stirred at room temperature for 2 hours. Water (20 mL) was added, and the mixture was extracted with ethyl acetate (20 mL x 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and the title product (50 mg, 55%) was obtained by column chromatography. LC-MS: m / z [M+H] + = 395.

[0397] Step 4: At 25°C, 8-(3-(2-acetylhydrazide-1-carbonyl)phenyl)-3-amino-N-propylimidazo[1,2-a]pyridine-2-carboxamide (20 mg, 0.05 mmol), p-toluenesulfonyl chloride (30 mg, 0.15 mmol), and triethylamine (15 mg, 0.15 mmol) were sequentially added to dichloromethane (3 mL). The mixture was stirred at 25°C for 16 hours. After concentration, the target product (3 mg, 16%) was obtained by column chromatography.

[0398] 1 H NMR (400 MHz, DMSO-d6) 8.70 (s, 1H), 8.41 (d, J = 8.0 Hz, 1H), 8.20 (d, J = 6.9 Hz, 1H), 8.03 (d, J = 7.7 Hz, 1H), 7.77 - 7.61 (m, 2H), 7.44 (d, J = 6.9 Hz, 1H), 6.98 (t, J = 6.9 Hz, 1H), 6.19 (s, 2H), 3.24 (dd, J = 13.4, 6.8 Hz, 2H), 2.60 (s, 3H), 1.54 (dd, J = 14.4, 7.2 Hz, 2H), 0.89 (t, J = 7.4 Hz, 3H). LC-MS: m / z [M+H] + = 377.

[0399] Example 44

[0400] [ka]

[0401] 3-amino-N-propyl-8-(3-pyridazin-4-yl)phenyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 4-(3-chlorophenyl)pyridazine 3-Chlorophenylboronic acid (200 mg, 1.3 mmol), 4-bromopyridazine (226 mg, 1.4 mmol), cesium carbonate (1.26 g, 3.9 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II) dichloride (84 mg, 0.13 mmol) were sequentially added to a mixture of dioxane and water (5 mL / 0.5 mL), protected with nitrogen gas, and stirred at 90°C for 1 hour. The mixture was concentrated, and the title product (120 mg, pale yellow solid) was obtained by column chromatography (petroleum ether:ethyl acetate = 2:1) with a yield of 48%. LC-MS: m / z [M+H] + = 191.

[0402] Step 2: 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyridazine 4-(3-chlorophenyl)pyridazine (120 mg, 0.63 mmol), bis(pinacolate)diborone (193 mg, 0.76 mmol), potassium acetate (185 mg, 1.9 mmol), X-Phos (56 mg, 0.13 mmol), and Pd2(dba)3 (28 mg, 0.03 mmol) were sequentially added to dioxane (5 mL), protected with nitrogen gas, and stirred at 100 °C for 16 hours. The mixture was concentrated and the title product (50 mg, yellow solid) was obtained by column chromatography with a yield of 28%. LC-MS: m / z [M+H] + =283.

[0403] Step 3: The procedure was the same as in the synthesis example of compound vii, using 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyridazine (50 mg, 0.177 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (52 mg, 0.19 mmol) as starting materials to obtain the title product (10 mg, yellow solid) in a yield of 15%.

[0404] 1HNMR(400 MHz, DMSO-d6) 9.75 (d, J = 1.2 Hz, 1H), 9.30 (d, J = 4.6 Hz, 1H), 8.53 (s, 1H), 8.38 (d, J = 7.9 Hz, 1H), 8.19 (d, J = 6.8 Hz, 1H), 8.12 (dd, J = 5.4, 2.5 Hz, 1H), 7.96 (d, J = 7.9 Hz, 1H), 7.78 (t, J = 6.0 Hz, 1H), 7.70 (t, J = 7.8 Hz, 1H), 7.50 (d, J = 6.6 Hz, 1H), 6.98 (t, J = 6.9 Hz, 1H), 6.18 (s, 2H), 3.24 (dd, J = 13.7, 6.6 Hz, 2H), 1.61 - 1.46 (m, 2H), 0.88 (t, J = 7.4 Hz, 3H) . LC-MS: m / z [M+H] + = 373.

[0405] Example 45

[0406] [ka]

[0407] 3-amino-8-(3-morpholinophenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, the target compound (35 mg, 42%) was obtained from (3-morpholinophenyl)boronic acid (50 mg, 0.22 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (65 mg, 0.22 mmol) as raw materials.

[0408] 1H NMR (400 MHz, DMSO-d6) 8.12 (d, J = 6.9 Hz, 1H), 7.67 (s, 1H), 7.62(t, J = 6.1 Hz, 1H), 7.50 (d, J = 7.7 Hz, 1H), 7.34 (t, J = 8.0 Hz, 1H), 7.29 (d, J = 6.9 Hz, 1H), 7.02 (dd, J = 8.3, 2.4 Hz, 1H), 6.92 (t, J = 6.9 Hz, 1H), 6.13(s, 2H), 3.82 - 3.71 (m, 4H), 3.24 (dd, J = 13.7, 6.7 Hz, 2H), 3.21 - 3.14 (m,4H), 1.52 (dd, J = 14.4, 7.2 Hz, 2H), 0.88 (t, J = 7.4 Hz, 3H). LC-MS: m / z [M+H] + = 380.

[0409] Example 46

[0410] [ka]

[0411] 3-amino-8-(3-fluorophenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (3-fluorophenyl)boronic acid (71 mg, 0.51 mmol) were used as raw materials to obtain the target product (35 mg, 33%), which was a yellow solid.

[0412] 1H NMR (400 MHz, DMSO-d6) 8.17 (d, J=6.85 Hz, 1 H) 7.95 - 8.09 (m, 2 H) 7.84 (br. s., 1 H) 7.46 - 7.60 (m, 1 H) 7.40 (d, J=6.85 Hz, 1 H) 7.25 LC-MS: m / z [M+1] + = 313.

[0413] Example 47

[0414] [ka]

[0415] 3-amino-N-propyl-8-(3-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (80 mg, 0.27 mmol) and (2-methoxyphenyl)boronic acid (62 mg, 0.41 mmol) were used as raw materials to obtain the target product (76 mg, 87%), which was a yellow solid.

[0416] 1H NMR (400 MHz, DMSO-d6) 8.52 (d, J=7.34 Hz, 1 H) 8.40 (s, 1 H) 8.20 (d, J=6.85 Hz, 1 H) 7.63 - 7.85 (m, 3 H) 7.45 (d, J=6.85 Hz, 1 H) 6.97 (t, J=6.72 Hz, 1 H) 6.21 (s, 2 H) 3.24 (q, J=6.68 Hz, 2 H) 1.44 - 1.61 (m, 2 H) 0.88 (t, J=7.34 Hz, 3 H). LC-MS: m / z [M+1] + = 363.

[0417] Example 48

[0418] [ka]

[0419] 3-amino-N-propyl-8-(3-(methyl)phenyl)imidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (80 mg, 0.27 mmol) and (2-methylphenyl)boronic acid (55 mg, 0.41 mmol) were used as raw materials to obtain the target product (53 mg, 64%), which was a yellow solid.

[0420] 1H NMR (400 MHz, DMSO-d6) 8.13 (d, J=6.60 Hz, 1 H) 7.92 (d, J=7.34 Hz, 1 H) 7.85 (br. s., 1 H) 7.75 (br. s., 1 H) 7.36 (t, J=7.46 Hz, 1 H) 7.24(dd, J=17.97, 6.97 Hz, 2 H) 6.92 (t, J=6.85 Hz, 1 H) 6.16 (br. s., 2 H) 3.23 (q, J=6.44 Hz, 2 H) 2.39 (s, 3 H) 1.45 - 1.57 (m, 2 H) 0.86 (t, J=7.09 Hz, 3 H).LC-MS: m / z [M+1] + = 309.

[0421] Example 49

[0422] [ka]

[0423] 3-amino-8-(2-methoxy-5-methylphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (80 mg, 0.27 mmol) and (2-methoxy-5-methylphenyl)boronic acid (45 mg, 0.27 mmol) were used as raw materials to obtain the target product (55 mg, 60%), which was a yellow solid.

[0424] 1H NMR (400 MHz, DMSO-d6) 8.09 (d, J=6.85 Hz, 1 H) 7.57 (br. s., 1 H) 7.15 - 7.29 (m, 2 H) 7.02 (d, J=8.31 ​​Hz, 1 H) 6.95 (d, J=6.36 Hz, 1 H) 6.87(d, J=6.85 Hz, 1 H) 6.11 (s, 2 H) 3.67 (s, 3 H) 3.17 (d, J=6.85 Hz, 2 H) 2.28 (s, 3 H) 1.47 (d, J=6.85 Hz, 2 H) 0.82 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 339.

[0425] Example 50

[0426] [ka]

[0427] 3-amino-8-(2-fluoro-5-methylphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and 2-fluoro-5-methylphenylboronic acid (52 mg, 0.34 mmol) were used as raw materials to obtain the target product (76 mg, 68%), which was a yellow solid.

[0428] 1H NMR (400 MHz, DMSO-d6) 8.17 (d, J=6.85 Hz, 1 H) 7.62 (br. s., 1 H) 7.50 (d, J=5.87 Hz, 1 H) 7.15 - 7.31 (m, 2 H) 7.07 (d, J=6.85 Hz, 1 H) 6.91(t, J=6.60 Hz, 1 H) 6.18 (br. s., 2 H) 3.13 - 3.25 (m, 2 H) 2.34 (s, 3 H) 1.42 - 1.54 (m, 2 H) 0.83 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 327.

[0429] Example 51

[0430] [ka]

[0431] 3-amino-8-(3-fluoro-5-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (90 mg, 0.30 mmol) and (3-fluoro-6-methoxyphenyl)boronic acid (76 mg, 0.45 mmol) were used as raw materials to obtain the target product (25 mg, 24%), which was a yellow solid.

[0432] 1H NMR (400 MHz, DMSO-d6) 8.12 (d, J=6.85 Hz, 1 H) 7.63 (br. s., 1 H) 7.37 (d, J=6.36 Hz, 1 H) 7.22 (d, J=7.83 Hz, 1 H) 7.16 (d, J=4.40 Hz, 1 H) 7.06 (d, J=6.85 Hz, 1 H) 6.88 (t, J=6.85 Hz, 1 H) 6.14 (br. s., 2 H) 3.71 (s, 3 H) 3.18 (d, J=6.85 Hz, 2 H) 1.40 - 1.54 (m, 2 H) 0.83 (t, J=7.34Hz, 3 H).LC-MS: m / z [M+1] + = 343.

[0433] Example 52

[0434] [ka]

[0435] 3-amino-8-(2,5-difluorophenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (2,5-difluorophenyl)boronic acid (54 mg, 0.34 mmol) were used as raw materials to obtain the target product (51 mg, 45%), which was a yellow solid.

[0436] 1H NMR (400 MHz, DMSO-d6) 8.20 (d, J=6.85 Hz, 1 H) 7.69 (br. s., 2 H) 7.28 - 7.46 (m, 2 H) 7.18 (d, J=6.36 Hz, 1 H) 6.94 (t, J=6.85 Hz, 1 H) 6.20(s, 2 H) 3.19 (q, J=6.52 Hz, 2 H) 1.44 - 1.55 (m, 2 H) 0.84 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 331.

[0437] Example 53

[0438] [ka]

[0439] 3-amino-8-(4-fluoro-2-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (4-fluoro-2-methoxyphenyl)boronic acid (87 mg, 0.51 mmol) were used as raw materials to obtain the target product (65 mg, 56%), which was a yellow solid.

[0440] 1 H NMR (400 MHz, DMSO-d6) 8.11 (d, J=6.85 Hz, 1 H) 7.59 (t, J=6.11 Hz, 1 H) 7.52 (t, J=7.83 Hz, 1 H) 6.96 - 7.09 (m, 2 H) 6.80 - 6.90 (m, 2 H)6.12 (s, 2 H) 3.74 (s, 3 H) 3.17 (q, J=6.85 Hz, 2 H) 1.41 - 1.54 (m, 2 H) 0.82 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 343.

[0441] Example 54

[0442] [ka]

[0443] 3-amino-8-(5-cyano-2-fluorophenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (60 mg, 0.20 mmol) and (5-cyano-2-fluorophenyl)boronic acid (49 mg, 0.30 mmol) were used as raw materials to obtain the target product (46 mg, 67%), which was a yellow solid.

[0444] 1 H NMR (400 MHz, DMSO-d6)8.16 - 8.31 (m, 2 H) 8.01 (dd, J=5.38, 3.42 Hz, 1 H) 7.71 (s, 1 H) 7.60 (t, J=9.29 Hz, 1 H) 7.19 (d, J=6.85 Hz, 1 LC-MS: m / z [M+1] + = 338.

[0445] Example 55

[0446] [ka]

[0447] 3-amino-8-(3-cyano-5-fluorophenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (80 mg, 0.27 mmol) and (3-cyano-5-fluorophenyl)boronic acid (67 mg, 0.41 mmol) were used as raw materials to obtain the target product (86 mg, 95%), which was a yellow solid.

[0448] 1 H NMR (400 MHz, DMSO-d6) 8.49 - 8.59 (m, 1 H) 8.44 (s, 1 H) 8.18 - 8.28 (m, 1 H) 7.81 - 7.98 (m, 2 H) 7.49 - 7.59 (m, 1 H) 6.93 - 7.03 (m, 1 LC-MS: m / z [M+1] + = 338.

[0449] Example 56

[0450] [ka]

[0451] 3-amino-8-(3-cyano-4-fluorophenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (3-cyano-4-fluorophenyl)boronic acid (112 mg, 0.68 mmol) were used as raw materials to obtain the target product (88 mg, 77%), which was a yellow solid.

[0452] 1H NMR (400 MHz, DMSO-d6) 8.66 (br. s., 2 H) 8.09 - 8.28 (m, 1 H) 7.82 - 7.96 (m, 1 H) 7.55 - 7.73 (m, 1 H) 7.33 - 7.52 (m, 1 H) 6.80 - 7.04 (m, 1H) 6.20 (br. s., 2 H) 3.23 (d, J=6.36 Hz, 2 H) 1.53 (d, J=6.85 Hz, 2 H) 0.87 (t, J=7.09 Hz, 3 H). LC-MS: m / z [M+1] + = 338.

[0453] Example 57

[0454] [ka]

[0455] 3-amino-8-(3-cyano-2-fluorophenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and 2-(5,5-dimethyl-1,3,2-dioxaborolan-2-yl)-3-methoxybenzonitrile (181 mg, 0.68 mmol) were used as raw materials to obtain the target product (28 mg, 24%), which was a yellow solid.

[0456] 1H NMR (400 MHz, DMSO-d6) 8.24 (d, J=6.85 Hz, 1 H) 8.13 - 8.20 (m, 1 H) 7.96 - 8.06 (m, 1 H) 7.68 - 7.77 (m, 1 H) 7.54 (s, 1 H) 7.21 (s, 1 H) 6.96 (s, 1 H) 6.23 (s, 2 H) 3.18 (d, J=7.34 Hz, 2 H) 1.49 (d, J=7.34 Hz, 2 H) 0.83 (t, J=7.34 Hz, 3 H). LC-MS: m / z [M+1] + = 338.

[0457] Example 58

[0458] [ka]

[0459] 3-amino-8-(2-methoxy-5-(trifluoromethyl)phenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (2-methoxy-5-(trifluoromethyl)phenyl)boronic acid (110 mg, 0.51 mmol) were used as raw materials to obtain the target product (94 mg, 70%), which was a yellow solid.

[0460] 1H NMR (400 MHz, DMSO-d6) 8.15 (d, J=6.85 Hz, 1 H) 7.71 - 7.83 (m, 2 H) 7.52 (t, J=6.11 Hz, 1 H) 7.34 (d, J=8.80 Hz, 1 H) 7.07 (d, J=6.85 Hz, 1H) 6.89 (t, J=6.85 Hz, 1 H) 6.14 (s, 2 H) 3.80 (s, 3 H) 3.17 (q, J=6.85 Hz, 2 H) 1.40 - 1.53 (m, 2 H) 0.83 (t, J=7.58 Hz, 3 H).LC-MS: m / z [M+1] + = 393.

[0461] Example 59

[0462] [ka]

[0463] 3-amino-8-(3-cyano-5-methylphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (3-cyano-5-methoxyphenyl)boronic acid (111 mg, 0.68 mmol) were used as raw materials to obtain the target product (50 mg, 44%), which was a yellow solid.

[0464] 1H NMR (400 MHz, DMSO-d6) 8.34 (s, 1 H) 8.27 (s, 1 H) 8.18 (s, 1 H) 7.77 - 7.86 (m, 1 H) 7.70 (s, 1 H) 7.41 (d, J=6.85 Hz, 1 H) 6.95 (s, 1 H) 6.20(s, 2 H) 3.24 (d, J=6.85 Hz, 2 H) 2.46 (s, 3 H) 1.53 (d, J=7.34 Hz, 2 H) 0.88 (t, J=7.34 Hz, 3 H). LC-MS: m / z [M+1] + = 334.

[0465] Example 60

[0466] [ka]

[0467] 3-amino-8-(5-cyano-2-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (90 mg, 0.30 mmol) and (5-cyano-2-methoxyphenyl)boronic acid (80 mg, 0.45 mmol) were used as raw materials to obtain the target product (19 mg, 18%), which was a yellow solid.

[0468] 1H NMR (400 MHz, DMSO-d6) 8.15 (d, J=6.85 Hz, 1 H) 7.84 - 7.94 (m, 2 H) 7.66 (s, 1 H) 7.33 (d, J=9.29 Hz, 1 H) 7.05 (d, J=6.85 Hz, 1 H) 6.89 (t, J=6.85 Hz, 1 H) 6.16 (s, 2 H) 3.81 (s, 3 H) 3.16 (d, J=6.85 Hz, 2 H) 1.41 - 1.51 (m, 2 H) 0.82 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 350.

[0469] Example 61

[0470] [ka]

[0471] 3-amino-8-(2-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (2-methoxyphenyl)boronic acid (77 mg, 0.51 mmol) were used as raw materials to obtain the target product (49 mg, 44%), which was a yellow solid.

[0472] 1H NMR (400 MHz, DMSO-d6) 8.11 (d, J=6.85 Hz, 1 H) 7.56 (br. s., 1 H) 7.47 (d, J=6.85 Hz, 1 H) 7.38 (t, J=7.70 Hz, 1 H) 7.13 (d, J=8.56 Hz, 1 H)6.95 - 7.06 (m, 2 H) 6.87 (t, J=6.85 Hz, 1 H) 6.12 (br. s., 2 H) 3.72 (s, 3 H) 3.10 - 3.22 (m, 2 H) 1.37 - 1.54 (m, 2 H) 0.82 (t, J=7.21 Hz, 3 H).LC-MS: m / z [M+1] + = 325.

[0473] Example 62

[0474] [ka]

[0475] 3-amino-8-(5-chloro-2-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (5-chloro-2-methoxyphenyl)boronic acid (95 mg, 0.51 mmol) were used as raw materials to obtain the target product (60 mg, 49%), which was a yellow solid.

[0476] 1H NMR (400 MHz, DMSO-d6) 8.13 (d, J=6.85 Hz, 1 H) 7.61 (s, 1 H) 7.38 - 7.51 (m, 2 H) 7.17 (d, J=8.80 Hz, 1 H) 7.02 (d, J=6.36 Hz, 1 H) 6.88 (t, J=6.85 Hz, 1 H) 6.15 (s, 2 H) 3.72 (s, 3 H) 3.17 (d, J=6.85 Hz, 2 H) 1.40 - 1.55 (m, 2 H) 0.83 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 359.

[0477] Example 63

[0478] [ka]

[0479] 3-amino-8-(2-fluoro-3-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (2-fluoro-3-methoxyphenyl)boronic acid (58 mg, 0.34 mmol) were used as raw materials to obtain the target product (92 mg, 79%), which was a yellow solid.

[0480] 1H NMR (400 MHz, DMSO-d6) 8.18 (d, J=6.85 Hz, 1 H) 7.62 (t, J=5.87 Hz, 1 H) 7.22 (d, J=3.42 Hz, 3 H) 7.07 (d, J=6.85 Hz, 1 H) 6.92 (t, J=6.85Hz, 1 H) 6.18 (s, 2 H) 3.88 (s, 3 H) 3.18 (q, J=6.85 Hz, 2 H) 1.42 - 1.54 (m, 2 H) 0.83 (t, J=7.34 Hz, 3 H). LC-MS: m / z [M+1] + = 343.

[0481] Example 64

[0482] [ka]

[0483] 3-amino-8-(2-fluoro-3-methylphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (80 mg, 0.27 mmol) and (2-fluoro-3-methylphenyl)boronic acid (62 mg, 0.41 mmol) were used as raw materials to obtain the target product (39 mg, 44%), which was a yellow solid.

[0484] 1H NMR (400 MHz, DMSO-d6) 8.17 (d, J=6.85 Hz, 1 H) 7.64 (t, J=5.87 Hz, 1 H) 7.52 (t, J=6.85 Hz, 1 H) 7.33 (t, J=7.34 Hz, 1 H) 7.14 - 7.24 (m, 1H) 7.08 (d, J=6.85 Hz, 1 H) 6.91 (t, J=6.85 Hz, 1 H) 6.18 (s, 2 H) 3.12 - 3.23 (m, 2 H) 2.30 (s, 3 H) 1.53-1.46 (m, 2 H) 0.83 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 327.

[0485] Example 65

[0486] [ka]

[0487] 3-amino-8-(2-fluoro-6-(methoxymethyl)phenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 2-Bromo-1-fluoro-3-(methoxymethyl)benzene 2-Bromo-1-(bromomethyl)-3-fluorobenzene (2 g, 7.46 mmol) and sodium methoxide (800 mg, 14.9 mmol) were dissolved in 10 mL of methanol and stirred at room temperature for 2 hours. 20 mL of water was added, and the mixture was extracted with dichloromethane (30 mL x 2). The organic phase was dried and concentrated to obtain 1.5 g of a white solid.

[0488] Step 2: 2-(2-fluoro-6-(methoxymethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 2-Bromo-1-fluoro-3-(methoxymethyl)benzene (220 mg, 1 mmol), bis(pinacolate)diborone (500 mg, 2 mmol), potassium acetate (300 mg, 3 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane adduct (CAS No.: 95464-05-4, 86 mg, 0.1 mmol) were dissolved in 5 mL of dioxane, heated to 100°C and stirred for 16 hours, 20 mL of water was added, and the mixture was extracted with dichloromethane (30 mL x 2). The organic phase was dried and concentrated to obtain the target product (181 mg, crude product), which was used directly in the next step.

[0489] Step 3: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and 2-(2-fluoro-6-(methoxymethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (181 mg, 0.68 mmol) were used as raw materials to obtain the target product (12 mg, 10%), which was a yellow solid.

[0490] 1 H NMR (400 MHz, DMSO-d6) 8.21 (d, J=6.85 Hz, 1 H) 7.61 (t, J=5.62 Hz, 1 H) 7.43 - 7.53 (m, 1 H) 7.37 (d, J=7.83 Hz, 1 H) 7.24 (t, J=8.80 Hz, 1 LC-MS: m / z [M+1] + = 357.

[0491] Example 66

[0492] [ka]

[0493] 3-amino-8-(3-chloro-2-fluorophenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (80 mg, 0.27 mmol) and (3-chloro-2-fluorophenyl)boronic acid (71 mg, 0.41 mmol) were used as raw materials to obtain the target product (35 mg, 38%), which was a yellow solid.

[0494] 1 H NMR (400 MHz, DMSO-d6) 8.21 (dd, J=6.85, 0.98 Hz, 1 H) 7.60 - 7.75 (m, 3 H) 7.34 (s, 1 H) 7.15 (d, J=6.85 Hz, 1 H) 6.90 - 6.97 (m, 1 H) 6.20(s, 2 H) 3.18 (d, J=7.34 Hz, 2 H) 1.48 (d, J=7.34 Hz, 2 H) 0.83 (t, J=7.58 Hz, 3 H).LC-MS: m / z [M+1] + = 347.

[0495] Example 67

[0496] [ka]

[0497] 3-amino-8-(5-(difluoromethyl)-2-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (5-(difluoromethyl)-2-methoxyphenyl)boronic acid (101 mg, 0.51 mmol) were used as raw materials to obtain the target product (54 mg, 55%), which was a yellow solid.

[0498] 1 H NMR (400 MHz, DMSO-d6) 8.14 (d, J=7.09 Hz, 1 H) 7.58 - 7.69 (m, 2 H) 7.55 (t, J=6.11 Hz, 1 H) 7.27 (d, J=8.56 Hz, 1 H) 6.85 - 7.17 (m, 3 LC-MS: m / z [M+1] + = 375.

[0499] Example 68

[0500] [ka]

[0501] 3-amino-8-(5-cyclopropyl-2-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (500 mg, 1.68 mmol) and (5-chloro-2-methoxyphenyl)boronic acid (470 mg, 2.52 mmol) were used as raw materials to obtain 3-amino-8-(5-chloro-2-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide (450 mg, 75%). Using this product (100 mg, 0.28 mmol) and cyclopropylboronic acid (36 mg, 0.42 mmol) as raw materials, and referring to the synthesis method of compound vii, the target product (50 mg, 49%) was obtained, which was a yellow solid.

[0502] 1H NMR (400 MHz, DMSO-d6) 8.09 (d, J=6.85 Hz, 1 H) 7.54 (br. s., 1 H) 6.92 - 7.19 (m, 4 H) 6.86 (t, J=6.60 Hz, 1 H) 6.11 (br. s., 2 H) 3.67 (s, 3 H)3.17 (d, J=6.36 Hz, 2 H) 1.90 (br. s., 1 H) 1.37 - 1.55 (m, 2 H) 0.77 - 0.96 (m, 5 H) 0.62 (d, J=3.42 Hz, 2 H).LC-MS: m / z [M+1] + = 365.

[0503] Example 69

[0504] [ka]

[0505] 3-amino-8-(2,5-dimethoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and 2,5-dimethoxyphenylboronic acid (62 mg, 0.34 mmol) were used as raw materials to obtain the target product (71 mg, 59%), which was a yellow solid.

[0506] 1 H NMR (400 MHz, CHLOROFORM) 7.76 (br. s., 1 H) 7.27 (br. s., 87 H) 6.92 - 7.04 (m, 2 H) 6.87 (br. s., 1 H) 5.02 (br. s., 1 H) 3.71 - 3.89 (m, 6H) 3.40 (d, J=6.85 Hz, 2 H) 1.56 - 1.73 (m, 2 H) 0.98 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 355.

[0507] Example 70

[0508] [ka]

[0509] 3-amino-8-(3-fluoro-5-(propa-1-in-1-yl)phenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 1-Bromo-3-fluoro-5-(propa-1-in-1-yl)benzene 1-Bromo-3-fluoro-5-iodobenzene (0.5 g, 1.66 mmol), 1-(trimethylsilyl)-1-propyne (0.19 g, 1.66 mmol), cuprous iodide (0.095 g, 0.50 mmol), and tetrakis(triphenylphosphine)palladium (0.15 g, 0.13 mmol) were dissolved in toluene (10 mL), the mixture was purged with air, and triethylamine (0.55 g, 5.48 mmol) and tetra-n-butylammonium fluoride (0.43 g, 1.66 mmol) were added to the reaction solution. The mixture was stirred at 100 °C for 16 hours. The solution was concentrated, 60 ml of water was added, and the mixture was extracted with ethyl acetate (60 ml x 2). The solution was concentrated again, and 300 mg of the product (85%, yellow liquid) was obtained by column chromatography (petroleum ether).

[0510] Step 2: 2-(3-fluoro-5-(prop-1-in-1-yl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 1-Bromo-3-fluoro-5-(prop-1-in-1-yl)benzene (0.2 g, 0.94 mmol), bis(pinacolate)diborone (CAS No.: 73183-34-3, 0.36 g, 1.41 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane adduct (0.077 g, 0.094 mmol), and potassium acetate (0.18 g, 1.88 mmol) were sequentially added to 1,4-dioxane (6 mL). The mixture was purged with nitrogen gas and reacted at 100 °C under microwave conditions for 1 hour. The mixture was concentrated, 40 ml of water was added, and then extracted with ethyl acetate (40 ml x 2). The mixture was concentrated to obtain 150 mg of the product (89%, yellow liquid).

[0511] Step 3: The procedure was the same as in the synthesis example of compound vii, using 2-(3-fluoro-5-(prop-1-in-1-yl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.11 g, 0.42 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (0.12 g, 0.42 mmol) as raw materials to obtain the product (40 mg, 27%), which was a yellow solid.

[0512] 1 HNMR (400MHz, DMSO-d6) 8.17 (d, J = 5.9 Hz, 1 H), 8.09 (d, J = 9.8 Hz, 1 H), 7.83 (s, 1 H), 7.77 (s, 1 H), 7.40 (d, J = 6.4 Hz, 1 H), 7.27 (d, LC-MS: m / z [M+1] + = 351.

[0513] Example 71

[0514] [ka]

[0515] 3-amino-8-(5-(7-ethyl-7H-imidazo[4,5-c]pyridazin-4-yl)-2-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 4-(3-chloro-4-methoxyphenyl)-7-ethyl-7H-imidazo[4,5-c]pyridazine The procedure was the same as in Example 39 (Step 1), and a yellow oily substance (300 mg, 35%) was obtained using 4-chloro-7-ethyl-7H-imidazo[4,5-c]pyridazine (546 mg, 3.0 mmol) and (3-chloro-4-methoxyphenyl)boronic acid (500 mg, 2.7 mmol) as raw materials. LC-MS: m / z [M+H] + = 289.

[0516] Step 2: 7-Ethyl-4-(4-Methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-7H-imidazo[4,5-c]pyridazine The procedure was the same as in Example 39 (Step 2), and a gray solid (90 mg, 50%) was obtained using 4-(3-chloro-4-methoxyphenyl)-7-ethyl-7H-imidazo[4,5-c]pyridazine (136 mg, 0.47 mmol) as the starting material. LC-MS: m / z [M+H] + =381.

[0517] Step 3: The procedure was the same as in the synthesis example of compound vii, using 7-ethyl-4-(4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-7H-imidazo[4,5-c]pyridazine (100 mg, 0.26 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (77 mg, 0.26 mmol) as raw materials to obtain the target product (9 mg, 7%).

[0518] 1H NMR (400 MHz, DMSO-d6) 9.51 (s, 1H), 8.79 (s, 1H), 8.61 (d, J = 2.1 Hz, 1H), 8.49 (dd, J = 8.8, 2.2 Hz, 1H), 8.17 (d, J = 6.9 Hz, 1H), 7.59 (t, J = 6.2 Hz, 1H), 7.39 (d, J = 8.9 Hz, 1H), 7.11 (d, J = 6.7 Hz, 1H), 6.93 (t, J = 6.9 Hz, 1H), 6.15 (s, 2H), 4.50 (q, J = 7.3 Hz, 2H), 3.84 (s, 3H), 3.15 (dd, LC-MS: m / z [M+H] + = 471.

[0519] Example 72

[0520] [ka]

[0521] 3-amino-8-(2-chloro-6-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (80 mg, 0.27 mmol) and (2-chloro-6-methoxyphenyl)boronic acid (71 mg, 0.49 mmol) were used as raw materials to obtain the target product (33 mg, 34%), which was a yellow solid.

[0522] 1H NMR (400 MHz, DMSO-d6) 8.14 (d, J=5.87 Hz, 1 H) 7.59 (t, J=5.87 Hz, 1 H) 7.32 - 7.47 (m, 1 H) 7.13 (dd, J=16.63, 8.31 Hz, 2 H) 6.78 - 6.96(m, 2 H) 6.15 (s, 2 H) 3.66 (s, 3 H) 3.09 - 3.20 (m, 2 H) 1.38 - 1.52 (m, 2 H) 0.81 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 359.

[0523] Example 73

[0524] [ka]

[0525] 3-amino-8-(2-cyano-6-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and 2-(5,5-dimethyl-1,3,2-dioxaborolan-2-yl)-3-methoxybenzonitrile (181 mg, 0.68 mmol) were used as raw materials to obtain the target product (28 mg, 24%), which was a yellow solid.

[0526] 1 H NMR (400 MHz, DMSO-d6)8.15 - 8.24 (m, 1 H) 7.47-7.66 (m, 4 H) 6.90-7.06 (m, 2 H) 6.19 (s, 2 H) 3.73 (s, 3 H) 3.16-3.12 (m, 2 H) 1.46 (d, J=7.34 Hz, 2 H) 0.81 (t, J=7.58 Hz, 3 H). LC-MS: m / z [M+1] + = 350.

[0527] Example 74

[0528] [ka]

[0529] 3-amino-8-(2-fluoro-6-(methylthio)phenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (80 mg, 0.27 mmol) and 6-fluoro-2-(methylsulfonyl)phenylboronic acid (50 mg, 0.27 mmol) were used as raw materials to obtain the target product (35 mg, 38%), which was a yellow solid.

[0530] 1 H NMR (400 MHz, DMSO-d6) 8.20 (d, J=6.36 Hz, 1 H) 7.59 (br. s., 1 H) 7.41 - 7.51 (m, 1 H) 7.03 - 7.26 (m, 1 H) 6.84 - 7.01 (m, 1 H) 6.19 (br. s., 2H) 3.15 (d, J=6.85 Hz, 1 H) 2.36 (s, 3 H) 1.40 - 1.55 (m, 2 H) 0.81 (t, J=7.09 Hz, 3 H). LC-MS: m / z [M+1] + = 359.

[0531] Example 75

[0532] [ka]

[0533] 3-amino-8-(2-fluoro-6-(trifluoromethoxy)phenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: (2-Fluoro-6-(trifluoromethoxy)phenyl)boronic acid 1-Fluoro-3-(trifluoromethoxy)benzene (500 mg, 2.78 mmol) was dissolved in tetrahydrofuran (12 mL), cooled to -78°C under the protection of argon gas, and lithium diisopropylamide tetrahydrofuran solution (2 M, 2.2 mL) was added dropwise. The mixture was stirred for 5 minutes, and trimethyl borate (578 mg, 5.56 mmol) tetrahydrofuran solution was added. The mixture was then stirred for another 10 minutes. 1 M aqueous HCl was added to the reaction solution to adjust the pH to 6, and the solution was extracted with diethyl ether. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated until a small amount of liquid remained, slurryed with n-heptane, and filtered by suction to obtain a white solid (200 mg, 32%).

[0534] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (2-fluoro-6-(trifluoromethoxy)phenyl)boronic acid (99 mg, 0.44 mmol) were used as raw materials to obtain the target product (32 mg, 24%), which was a pale yellow solid.

[0535] 1 HNMR (400MHz, DMSO-d6) 8.36 - 8.24 (m, 1 H), 7.69 - 7.60 (m, 1 H), 7.58 - 7.50 (m, 1 H), 7.47 - 7.34 (m, 2 H), 7.09 - 7.01 (m, 1 H), 6.98 - 6.89 (m, 1 H), 6.33 - 6.14 (m, 2 H), 3.20 - 3.11 (m, 2 H), 1.50 - 1.42 (m, 2 H), 0.83-0.79 (m, 3 H). LC-MS: m / z [M+1] + = 397.

[0536] Example 76

[0537] [ka]

[0538] 3-amino-8-(2,3-difluoro-6-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (90 mg, 0.30 mmol) and (2,3-difluoro-6-methoxyphenyl)boronic acid (85 mg, 0.45 mmol) were used as raw materials to obtain the target product (9 mg, 8%), which was a yellow solid.

[0539] 1 H NMR (400 MHz, DMSO-d6) 8.19 (d, J=6.36 Hz, 1 H) 7.64 (br. s., 1 H) 7.48 (d, J=9.29 Hz, 1 H) 6.87 - 7.06 (m, 3 H) 6.18 (br. s., 2 H) 3.69 (s, 3H) 3.15 (br. s., 2 H) 1.38 - 1.56 (m, 2 H) 0.81 (t, J=7.09 Hz, 3 H).LC-MS: m / z [M+1] + = 361.

[0540] Example 77

[0541] [ka]

[0542] 3-amino-8-(2-fluoro-6-methoxy-3-methylphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (90 mg, 0.30 mmol) and (2-fluoro-6-methoxy-3-methylphenyl)boronic acid (83 mg, 0.45 mmol) were used as raw materials to obtain the target product (36 mg, 34%), which was a yellow solid.

[0543] 1 H NMR (400 MHz, DMSO-d6) 8.02 - 8.22 (m, 1 H) 7.61 (s, 1 H) 7.28 (s, 1 H) 6.77 - 6.94 (m, 3 H) 6.15 (s, 2 H) 3.65 (s, 3 H) 3.16 (dd, J=9.05, 4.65Hz, 2 H) 2.20 (s, 3 H) 1.46 (d, J=7.34 Hz, 2 H) 0.81 (t, J=7.58 Hz, 3 H).LC-MS: m / z [M+1] + = 357.

[0544] Example 78

[0545] [ka]

[0546] 3-amino-8-(6-fluoro-2-methoxy-3-methylphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (6-fluoro-2-methoxy-3-methylphenyl)boronic acid (94 mg, 0.51 mmol) were used as raw materials to obtain the target product (90 mg, 74%), which was a yellow solid.

[0547] 1 H NMR (400 MHz, DMSO-d6) 8.18 (d, J=6.85 Hz, 1 H) 7.62 (s, 1 H) 7.30 (s, 1 H) 6.95 - 7.03 (m, 2 H) 6.86 - 6.94 (m, 1 H) 6.18 (s, 2 H) 3.41 (s, 3H) 3.14 (d, J=7.34 Hz, 2 H) 2.25 (s, 3 H) 1.39 - 1.55 (m, 2 H) 0.80 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] += 357.

[0548] Example 79

[0549] [ka]

[0550] 3-amino-8-(3,6-difluoro-2-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (3,6-difluoro-2-methoxyphenyl)boronic acid (96 mg, 0.51 mmol) were used as raw materials to obtain the target product (55 mg, 45%), which was a yellow solid.

[0551] 1 H NMR (400 MHz, DMSO-d6) 8.21 (d, J=5.87 Hz, 1 H) 7.70 (t, J=6.11 Hz, 1 H) 7.42 (ddd, J=11.25, 9.29, 5.38 Hz, 1 H) 7.11 (td, J=8.80, 3.91 Hz, 1H) 7.03 (d, J=5.87 Hz, 1 H) 6.88 - 6.95 (m, 1 H) 6.20 (s, 2 H) 3.74 (d, J=1.47 Hz, 3 H) 3.08 - 3.21 (m, 2 H) 1.41 - 1.53 (m, 2 H) 0.81 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 361.

[0552] Example 80

[0553] [ka]

[0554] 3-amino-8-(2-fluoro-6-methoxyphenyl-5-chloro)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (2-fluoro-6-methoxyphenyl-5-chloro)boronic acid (187 mg, 0.68 mmol) were used as raw materials to obtain the target product (20 mg, 16%), which was a yellow solid.

[0555] 1 H NMR (400 MHz, DMSO-d6)8.22 (d, J=6.85 Hz, 1 H) 7.69 (s, 1 H) 7.63 (dd, J=8.80, 5.87 Hz, 1 H) 7.20 (t, J=8.80 Hz, 1 H) 7.06 (d, J=6.36 Hz, LC-MS: m / z [M+1] + = 377.

[0556] Example 81

[0557] [ka]

[0558] 3-amino-8-(2,4-dimethoxypyrimidine-5-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (120 mg, 0.40 mmol) and 2,4-dimethoxypyrimidine-5-boronic acid (74 mg, 0.40 mmol) were used as raw materials to obtain the target product (108 mg, 76%), which was a yellow solid.

[0559] 1 H NMR (400 MHz, DMSO-d6) 8.80 (s, 1 H) 8.13 (d, J=6.85 Hz, 1 H) 7.77 (s, 1 H) 7.22 (d, J=6.85 Hz, 1 H) 6.90 (t, J=7.09 Hz, 1 H) 6.15 (s, 2 LC-MS: m / z [M+1] + = 357.

[0560] Example 82

[0561] [ka]

[0562] 3-amino-8-(2-methoxypyridine-3-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (2-methoxypyridine-3-yl)boronic acid (52 mg, 0.34 mmol) were used as raw materials to obtain the target product (45 mg, 41%), which was a yellow solid.

[0563] 1H NMR (400 MHz, DMSO-d6) 8.22 (dd, J=4.89, 1.47 Hz, 1 H) 8.14 (d, J=6.36 Hz, 1 H) 8.05 (dd, J=7.34, 1.96 Hz, 1 H) 7.65 (s, 1 H) 7.07 - 7.20 (m,2 H) 6.90 (t, J=6.85 Hz, 1 H) 6.15 (s, 2 H) 3.83 (s, 3 H) 3.12 - 3.23 (m, 2 H) 1.41 - 1.54 (m, 2 H) 0.83 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 326.

[0564] Example 83

[0565] [ka]

[0566] 3-amino-8-(2-methoxy-5-methylpyridine-3-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 2-Methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine 3-Bromo-2-methoxy-5-methylpyridine (300 mg, 1.5 mmol), bis(pinacolate)diborone (455 mg, 1.8 mmol), potassium acetate (661 mg, 4.5 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (55 mg, 0.075 mmol) were sequentially added to N,N-dimethylformamide (5 mL), and the mixture was stirred at 80°C for 16 hours under the protection of nitrogen gas. The title product (234 mg, yield: 62.5%) was obtained by column chromatography (petroleum ether:ethyl acetate = 2:1), and was a white liquid. LC-MS: m / z [M+H] + =250.

[0567] Step 2: The procedure was the same as in the synthesis example of compound vii, using 2-methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (50 mg, 0.2 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (59 mg, 0.2 mmol) as starting materials to obtain the title product (18 mg, yield: 27%), which was a yellow solid.

[0568] 1 HNMR(400 MHz, DMSO-d6) 8.18-8.12 (m, 1H), 8.04 (s, 1H), 7.82 (d, J = 2.2 Hz, 1H), 7.65-7.59 (m, 1H), 7.15-7.10 (m, 1H), 6.93-6.88 (m, 1H), 6.14 (s, 2H), 3.79 (s, 3H), 3.18 (dd, J = 13.6, 6.8 Hz, 2H), 2.29 (s, 3H), 1.49 (dd, J = 14.5, 7.3 Hz, 2H), 0.84 (t, J = 7.4 Hz, 3H) LC-MS: m / z [M+H] + =340.

[0569] Example 84

[0570] [ka]

[0571] 3-amino-8-(5-fluoro-2-methoxypyridine-3-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 5-Fluoro-2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine The procedure was the same as in Example 83 (Step 1), and a gray solid (2.0 g, 70%) was obtained using 3-bromo-5-fluoro-2-methoxypyridine (2.0 g, 9.8 mmol) as the starting material. LC-MS: m / z [M+H] + = 254.

[0572] Step 2: The procedure was the same as in the synthesis example of compound vii, using 5-fluoro-2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (64.8 mg, 0.26 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (50 mg, 0.17 mmol) as raw materials to obtain the title compound (29 mg, yield: 50%).

[0573] 1 H NMR (400 MHz, DMSO) 8.22 (d, J = 3.0 Hz, 1H), 8.19 - 8.10 (m, 2H), 7.71 (t, J = 6.2 Hz, 1H), 7.27 (d, J = 6.3 Hz, 1H), 6.92 (t, J = 6.9 Hz, 1H), 6.17 (s, 2H), 3.84 (d, J = 7.8 Hz, 3H), 3.19 (dd, J = 14.0, 6.5 Hz, 2H), 1.49 (dd, J = 14.5, 7.3 Hz, 2H), 0.84 (t, J = 7.4 Hz, 3H). LC-MS: m / z [M+H] + = 344.

[0574] Example 85

[0575] [ka]

[0576] 3-amino-8-(4-methoxypyridine-3-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (80 mg, 0.27 mmol) and (4-methoxypyridine-3-yl)boronic acid (41 mg, 0.27 mmol) were used as raw materials to obtain the target product (39 mg, 44%), which was a yellow solid.

[0577] 1 H NMR (400 MHz, DMSO-d6) 8.43 - 8.64 (m, 2 H) 8.15 (d, J=6.85 Hz, 1 H) 7.63 (br. s., 1 H) 7.17 - 7.28 (m, 1 H) 7.10 (d, J=6.36 Hz, 1 H) 6.85 -6.93 (m, 1 H) 6.15 (s, 2 H) 3.82 (s, 3 H) 3.17 (d, J=7.34 Hz, 2 H) 1.42 - 1.53 (m, 2 H) 0.82 (t, J=7.58 Hz, 3 H).LC-MS: m / z [M+1] + = 326.

[0578] Example 86

[0579] [ka]

[0580] 3-amino-8-(2-methylpyridine-4-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (80 mg, 0.27 mmol) and (2-methylpyridine-4-yl)boronic acid (55 mg, 0.41 mmol) were used as raw materials to obtain the target product (77 mg, 92%), which was a yellow solid.

[0581] 1H NMR (400 MHz, DMSO-d6) 8.53 (d, J=5.38 Hz, 1 H) 8.22 (d, J=6.85 Hz, 1 H) 7.97 - 8.12 (m, 2 H) 7.89 (t, J=5.87 Hz, 1 H) 7.52 (d, J=6.85 Hz, 1H) 6.97 (t, J=6.85 Hz, 1 H) 6.21 (s, 2 H) 3.20 - 3.28 (m, 2 H) 2.54 - 2.62 (m, 3 H) 1.47 - 1.62 (m, 2 H) 0.88 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 310.

[0582] Example 87

[0583] [ka]

[0584] 3-amino-8-(5-methylpyridine-3-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (90 mg, 0.30 mmol) and (5-methylpyridine-3-yl)boronic acid (62 mg, 0.45 mmol) were used as raw materials to obtain the target product (68 mg, 72%), which was a yellow solid.

[0585] 1H NMR (400 MHz, DMSO-d6) 9.14 (br. s., 1 H) 8.46 (br. s., 1 H) 8.30 (br. s., 1 H) 8.18 (d, J=6.85 Hz, 1 H) 7.82 (t, J=5.62 Hz, 1 H) 7.39 (d, J=6.85Hz, 1 H) 6.95 (t, J=6.85 Hz, 1 H) 6.19 (s, 2 H) 3.23 (q, J=6.36 Hz, 2 H) 2.40 (s, 3 H) 1.42 - 1.63 (m, 2 H) 0.87 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 310.

[0586] Example 88

[0587] [ka]

[0588] 3-amino-8-(5-cyanopyridine-3-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (90 mg, 0.30 mmol) and 5-cyano-3-pyridylboronic acid (44 mg, 0.30 mmol) were used as raw materials to obtain the target product (66 mg, 62%), which was a yellow solid.

[0589] 1H NMR (400 MHz, DMSO-d6) 9.60 - 9.78 (m, 1 H) 9.05 (d, J=8.31 ​​Hz, 2 H) 8.18 - 8.32 (m, 1 H) 7.90 - 8.07 (m, 1 H) 7.46 - 7.67 (m, 1 H) 6.91 -7.08 (m, 1 H) 6.24 (br. s., 2 H) 3.24 (d, J=5.38 Hz, 2 H) 1.44 - 1.61 (m, 2 H) 0.75 - 0.97 (m, 3 H).LC-MS: m / z [M+1] + = 321.

[0590] Example 89

[0591] [ka]

[0592] 3-amino-8-(2-cyanopyridine-4-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as that for the synthesis of compound vii. Using 4-(4,4,5,5-tetramethyl-1,3,2-dioxybenzofuran-2-yl)pyridinecarbonitride (55 mg, 0.24 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (71 mg, 0.24 mmol) as raw materials, the title product (4 mg, yield: 5%) was obtained, which was a yellow solid.

[0593] 1HNMR (400 MHz, DMSO) 8.84 (d, J = 5.6 Hz, 3H), 8.31 (d, J = 6.9 Hz, 1H), 8.05 (t, J = 6.0 Hz, 1H), 7.78 (d, J = 7.0 Hz, 1H), 7.03 (t, J = 7.0 Hz, 1H), 6.26 (s, 2H), 3.26 (dd, J = 13.9, 6.6 Hz, 2H), 1.56 (dd, J = 14.5, 7.3 Hz, 2H), 0.90 (t, J = 7.4 Hz, 3H). LC-MS: m / z [M+H] + =321.

[0594] Example 90

[0595] [ka]

[0596] 3-amino-8-(2-fluoropyridine-3-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (2-fluoropyridine-3-yl)boronic acid (96 mg, 0.68 mmol) were used as raw materials to obtain the target product (27 mg, 26%), which was a white solid.

[0597] 1 H NMR (400 MHz, DMSO-d6)8.45 (br. s., 1 H) 8.16 - 8.36 (m, 1 H) 7.71 (br. s., 1 H) 7.50 (br. s., 1 H) 7.25 (d, J=5.38 Hz, 1 H) 6.96 (d, J=6.85 Hz,2 H) 6.20 (br. s., 1 H) 3.19 (d, J=6.85 Hz, 2 H) 1.49 (d, J=6.36 Hz, 2 H) 0.84 (br. s., 3 H).LC-MS: m / z [M+1]+ = 314.

[0598] Example 91 (B region condensed ring)

[0599] [ka]

[0600] 3-amino-8-(6-methoxy-4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (80 mg, 0.27 mmol) and 6-methoxy-4-methyl-7-(tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-1,4-benzoxazin-3-one (86 mg, 0.27 mmol) were used as raw materials to obtain the target product (58 mg, 53%), which was a yellow solid.

[0601] 1 H NMR (400 MHz, DMSO-d6) 8.06 - 8.12 (m, 1 H) 7.52 - 7.60 (m, 1 H) 7.15 (s, 1 H) 7.00 (s, 1 H) 6.92 (s, 1 H) 6.86 (s, 1 H) 6.11 (s, 2H) 4.63 (s, 2H) 3.76 (s, 3 H) 3.37 (br. s., 3 H) 3.18 (d, J=7.34 Hz, 2 H) 1.48 (d, J=6.85 Hz, 2 H) 0.83 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 410.

[0602] Example 92

[0603] [ka]

[0604] 3-amino-8-(6-methoxy-4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 6-Methoxy-4-methyl-7-(tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-1,4-benzoxazine 6-Methoxy-4-methyl-7-(tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-1,4-benzoxazin-3-one (600 mg, 1.8 mmol) was dissolved in 10 mL of 2 M borane-tetrahydrofuran solution, the tube was sealed, heated to 80°C and stirred for 16 hours, cooled, the reaction solution was concentrated, methanol was added and quenched, the solution was concentrated again, and purified on a preparative plate (petroleum ether:ethyl acetate = 10:1) to obtain the target product (310 mg, 52%).

[0605] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (300 mg, 1 mmol) and 6-methoxy-4-methyl-7-(tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-1,4-benzoxazine (310 mg, 1 mmol) were used as raw materials to obtain the target product (25 mg, 7%), which was a yellow solid.

[0606] 1H NMR (400 MHz, DMSO-d6) 7.94 - 8.07 (m, 1 H) 7.42 - 7.61 (m, 1 H) 6.91 - 6.99 (m, 1 H) 6.78 - 6.88 (m, 2 H) 6.46 (s, 1 H) 6.07 (s, 1 H) 4.19 (br.s., 2 H) 3.67 (s, 3 H) 3.27 (br. s., 2 H) 3.15 - 3.22 (m, 2 H) 2.92 (s, 3 H) 1.40 - 1.55 (m, 2 H) 0.84 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 396.

[0607] Example 93

[0608] [ka]

[0609] 3-amino-8-(5-methoxy-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-6-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 5-Methoxybenzo[d]oxazole-2(3H)-one 2-amino-4-methoxyphenol (5.01 g, 35.93 mmol) was dissolved in anhydrous dichloromethane (100 mL), CDI (6.41 g, 39.53 mmol) was added in batches, the mixture was stirred at room temperature for 16 hours, quenched with water (100 mL), separated, the organic layer was collected, the aqueous phase was extracted with dichloromethane (100 mL x 3), and the mixture was tumble-dried to obtain the crude product. After purification by reverse-phase column chromatography (0.5% NH3, H2O - acetonitrile), the collected product was extracted with ethyl acetate (200 mL x 3), washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, and the tumble-dried product was slurryed with petroleum ether to obtain the title product (3.41 g, white solid) with a yield of 57.5%.

[0610] Step 2: 6-bromo-5-methoxybenzo[d]oxazole-2(3H)-one 5-Methoxybenzo[d]oxazole-2(3H)-one (2.01 g, 12.12 mmol) was dissolved in glacial acetic acid (20.0 mL), hydrobromic acid (33% acetic acid solution) (7.43 g, 30.30 mmol) was added, the mixture was stirred at room temperature for 30 minutes, cooled to 10°C, hydrogen peroxide (concentration: 30%) (1.79 g, 15.76 mmol) was slowly added, the temperature was controlled not to exceed 10°C, and the mixture was raised to room temperature and reacted for 2 hours. The reaction solution was poured into 100 mL of water, stirred for 30 minutes, filtered, the cake was washed twice with water, the cake was collected, and the mixture was vacuum-dried to obtain the title product (1.80 g, white solid) in a yield of 60.8%.

[0611] Step 3: 6-Bromo-5-methoxy-3-methylbenzo[d]oxazole-2(3H)-one 6-Bromo-5-methoxybenzo[d]oxazole-2(3H)-one (1.01 g, 4.10 mmol) was dissolved in DMSO (20.0 mL). Methyl iodide (7.66 mL, 123.01 mmol) and potassium carbonate (1.13 g, 8.20 mmol) were added at room temperature, and the mixture was reacted for 16 hours at room temperature. The reaction was quenched with water (100 mL), extracted with ethyl acetate (50 mL x 3), washed with saturated saline (50 mL), and rotated-dried to obtain the crude product. After purification by reverse-phase column chromatography (0.5% TFA-acetonitrile), the title product (510.1 mg, pink solid) was obtained, with a yield of 48.2%.

[0612] Step 4: 5-Methoxy-3-methyl-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1,3-benzoxazole-2-one 6-Bromo-5-methoxy-3-methylbenzo[d]oxazole-2(3H)-one (110 mg, 0.43 mmol), bis(pinacolate)diborone (220 mg, 0.86 mmol), potassium acetate (130 mg, 1.29 mmol), triethylamine (130 mg, 1.29 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (CAS (CAS No.: 564483-18-7, 20 mg, 0.04 mmol) and trisdibenzylideneacetone dipalladium (CAS No.: 51364-51-3, 39 mg, 0.04 mmol) were dissolved in 5 mL of dioxane, heated to 100°C and stirred for 16 hours. The organic phase was purified on a preparative plate (petroleum ether:ethyl acetate = 10:1) to obtain the target product (90 mg, white solid) with a yield of 77%.

[0613] Step 5: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (80 mg, 0.27 mmol) and 5-methoxy-3-methyl-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1,3-benzoxazole-2-one (82 mg, 0.27 mmol) were used as raw materials to obtain the target product (18 mg, 17%), which was a yellow solid.

[0614] 1 H NMR (400 MHz, DMSO-d6) 8.07 - 8.14 (m, 1 H) 7.57 - 7.63 (m, 1 H) 7.45 - 7.51 (m, 1 H) 7.16 - 7.21 (m, 1 H) 7.00 - 7.05 (m, 1 H) 6.85 - 6.91(m, 1 H) 6.08 - 6.15 (m, 2 H) 3.77 (s, 3 H) 3.41 (s, 3 H) 3.14 - 3.21 (m, 2 H) 1.43 - 1.51 (m, 2 H) 0.82 (s, 2 H).LC-MS: m / z [M+1] + = 396.

[0615] Example 94

[0616] [ka]

[0617] 3'-amino-7-methoxy-N-propyl-[6,8'-diimidazo[1,2-a]pyridine]-2'-carboxamide Step 1: 5-Bromo-4-methoxy-2-aminopyridine 4-methoxypyridine-2-amine (3 g, 24.2 mmol) was added to 30 ml of DMF, and NBS (5.2 g, 29 mmol) was added in batches. The mixture was stirred at room temperature for 3 hours. The reaction solution was added to 200 ml of water, a red solid precipitated, which was filtered and dried to obtain 3 g of the title product. The yield was 71%. LC-MS: m / z [M+H] + = 203.

[0618] Step 2: 6-bromo-7-methoxyimidazo[1,2-a]pyridine 5-Bromo-4-methoxy-2-aminopyridine (1 g, 4.95 mmol), chloroacetaldehyde (465 mg, 59 mmol), and sodium carbonate (1.24 g, 11.7 mmol) were added to 16 mL of ethanol and 4 mL of water, and the mixture was stirred at 80°C for 16 hours. The reaction solution was added to 20 mL of water, extracted with ethyl acetate (30 mL x 3), concentrated, and obtained the title product (395 mg, brown solid) by column chromatography (petroleum ether:ethyl acetate = 3:1) with a yield of 38%. LC-MS: m / z [M+H] + = 227.

[0619] Step 3: 7-Methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine Under the protection of nitrogen gas, 6-bromo-7-methoxyimidazo[1,2-a]pyridine (300 mg, 1.3 mmol), bis(pinacolate)diborone (363 mg, 1.43 mmol), potassium acetate (386 mg, 3.9 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane adduct (95 mg, 0.1 mmol) were sequentially added to dioxane (5 mL), and the mixture was stirred at 130°C for 2 hours under microwave. Water (20 mL) was added, and the mixture was extracted with ethyl acetate (30 mL x 3) and concentrated to obtain the title product (260 mg, crude product). LC-MS: m / z [M+H] + =275.

[0620] Step 4: The procedure was the same as in the synthesis example of compound vii, using 7-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine (260 mg of crude product, 0.95 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) as starting materials to obtain the title product (4 mg, yellow solid) in a yield of 3%.

[0621] 1 H NMR (400 MHz, DMSO) δ 8.72 (s, 1H), 8.16 (d, J = 6.4 Hz, 1H), 7.80 (s, 1H), 7.75 (t, J = 5.8 Hz, 1H), 7.45 (s, 1H), 7.14 (d, J = 6.6 Hz, 1H), 7.08 (s, 1H), 6.91 (t, J = 6.8 Hz, 1H), 6.15 (s, 2H), 3.78 (s, 3H), 3.16 (dd, J = 13.2, 6.4 Hz, 2H), 1.47 (dd, J = 14.4, 7.2 Hz, 2H), 0.82 (t, J = 7.3 Hz, 3H). LC-MS: m / z [M+H] + = 365.

[0622] Example 95

[0623] [ka]

[0624] 3-amino-8-(6-methoxy-1-methyl-1H-indazole-5-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 5-bromo-6-methoxy-1-methyl-1H-indazole (and 5-bromo-6-methoxy-2-methyl-2H-indazole) 5-bromo-6-methoxy-1H-indazole (350 mg, 1.54 mmol) was dispersed in DMF (10 mL), sodium hydride (74.3 mg, 1.54 mmol) was added, and the mixture was stirred for 0.5 hours. Then, methyl iodide (440 mg, 3.09 mmol) was added. The mixture was stirred at room temperature for 5 hours. After filtration and concentration, the target products 5-bromo-6-methoxy-1-methyl-1H-indazole (95 mg) and 5-bromo-6-methoxy-2-methyl-2H-indazole (110 mg) were obtained by column chromatography, with a total yield of 55%. LC-MS: m / z [M+H] + =241.

[0625] Step 2: 6-Methoxy-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole The procedure was the same as in Example 94 (Step 3), and a white powder (35 mg, 58%) was obtained using 5-bromo-6-methoxy-1-methyl-1H-indazole (50 mg, 0.21 mmol) as the raw material. LC-MS: m / z [M+1] = 289.

[0626] Step 3: Using a procedure similar to that of the synthesis example of compound vii, the target product (20 mg, 44%) was obtained using 6-methoxy-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (35 mg, 0.12 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (36 mg, 0.12 mmol) as raw materials.

[0627] 1 H NMR (400 MHz, DMSO-d6) 8.11 (d, J = 6.8 Hz, 1H), 7.96 (s, 1H), 7.74 (s, 1H), 7.55 (s, 1H), 7.24 (s, 1H), 6.99 (d, J = 6.7 Hz, 1H), 6.88 (s, 1H), 6.11 (s, 2H), 4.05 (s, 3H), 3.80 (s, 3H), 3.21 - 3.09 (m, 2H), 1.45 (d, J = 7.1 Hz, 2H), 0.81 (t, J = 7.4 Hz, 3H). LC-MS: m / z [M+1]= 379.

[0628] Example 96

[0629] [ka]

[0630] 3-amino-8-(6-methoxy-2-methyl-2H-indazole-5-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 6-Methoxy-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole The procedure was the same as in Example 94 (Step 3), and a pale white powder (60 mg, 49.6%) was obtained using 5-bromo-6-methoxy-2-methyl-2H-indazole (100 mg, 0.42 mmol) as the raw material. LC-MS: m / z [M+1] + = 289.

[0631] Step 2: Using the same procedure as in the synthesis example of compound vii, the target compound (20 mg, 31%) was obtained using 6-methoxy-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole (50 mg, 0.17 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (51 mg, 0.17 mmol) as raw materials.

[0632] 1 H NMR (400 MHz, DMSO-d6) 8.25 (s, 1H), 8.10 (d, J = 6.1 Hz, 1H), 7.71 (s, 1H), 7.53 (t, J = 6.2 Hz, 1H), 7.04 (s, 1H), 6.98 (d,J = 6.7 Hz, 1H), 6.87 (t, J = 6.9 Hz, 1H), 6.10 (s, 2H), 4.12 (s, 3H), 3.73 (d, J = 7.9 Hz, 3H), 3.14 (d, J = 19.4, 9.7 Hz, 2H), 1.55 - 1.38 (m, 2H), 0.89 - 0.71 (m, 3H). LC-MS: m / z [M+1] + = 379.

[0633] Example 97

[0634] [ka]

[0635] 3-amino-8-(7-methoxyquinoline-6-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 7-Methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline The procedure was the same as in Example 94 (Step 3), and the title compound (220 mg, 92%) was obtained using 6-bromo-7-methoxyquinoline (200 mg, 0.84 mmol) as a starting material. It was a yellow solid. LC-MS: m / z [M+H] + = 286.

[0636] Step 2: Using the same procedure as in the synthesis example of compound vii, 7-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline (200 mg, 0.7 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (208 mg, 0.7 mmol) were used as raw materials to obtain the target compound (100 mg, 35%), which was a yellow solid.

[0637] 1 H NMR (400 MHz, CHLOROFORM-d) 0.93 (t, J=7.34 Hz, 3 H) 1.58 (d, J=7.34 Hz, 2 H) 3.34 (d, J=6.85 Hz, 2 H) 3.97 (s, 3 H) 4.97 - 5.10 (m, 2 H)6.88 - 6.98 (m, 1 H) 7.36 - 7.49 (m, 2 H) 7.76 - 7.88 (m, 2 H) 8.15 (br. s., 1 H) 8.25 - 8.36 (m, 1 H) 8.83 - 8.93 (m, 1 H). LC-MS: m / z [M+H] + = 376.

[0638] Example 98

[0639] [ka]

[0640] 3-amino-8-(6-fluorobenzo[d]oxazole-5-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 2-amino-4-bromo-5-fluorophenol 3612 mg, 19.05 mmol of tin(II) chloride was added to a 25 mL solution of 4-bromo-5-fluoro-2-nitrophenol (900 mg, 3.81 mmol) in ethanol, and the mixture was heated under reflux and stirred for 2 hours. The reaction solution was concentrated, and the residue was added to an aqueous sodium bicarbonate solution to adjust the pH of the solution to 8. Extraction was performed with ethyl acetate (100 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to obtain the target product (500 mg, 64%), which was a pale yellow solid. LCMS: m / z [M+H] + = 206.

[0641] Step 2: 5-bromo-6-fluorobenzo[d]oxazole 2-amino-4-bromo-5-fluorophenol (300 mg, 1.46 mmol) and p-toluenesulfonic acid (251 mg, 1.46 mmol) were dissolved in trimethyl orthoformate (2 mL) and stirred at 90°C for 2 hours. The reaction solution was concentrated and purified by column chromatography (petroleum ether:ethyl acetate = 30:1 to 10:1) to obtain the target product (300 mg, 95%), which was a pale yellow solid. :m / z [M+H] + = 216.

[0642] Step 3: 6-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-diboran-2-yl)benzo[d]oxazole 5-bromo-6-fluorobenzo[d]oxazole (60 mg, 0.28 mmol), bis(pinacolate)diborone (424 mg, 1.67 mmol), potassium acetate (273 mg, 2.78 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane adduct (114 mg, 0.14 mmol) were sequentially added to 1,4-dioxane (12 mL), protected with argon gas, and stirred at 100°C for 16 hours. The reaction solution was used directly in the next step.

[0643] Step 4: To the reaction solution from the previous step, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol), cesium carbonate (371 mg, 1.14 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane adduct (31 mg, 0.038 mmol), and water (2.5 mL) were added and the mixture was stirred at 100°C for 5 hours. The reaction solution was filtered through diatomaceous earth, the filtrate was concentrated, and the solution was purified by column chromatography to obtain the target product (38 mg, 2-step yield: 38%).

[0644] 1 H NMR (400MHz, CHLOROFORM-d) 8.15 -8.02 (m, 3 H), 7.45 (d, J = 8.8 Hz, 1 H), 7.30 (br.s., 1 H), 6.97 (br. s., 1 H), 3.36-3.32 (m, 2 H), 1.68 - 1.50 (m, 2 H), 0.94 (t, J = 7.3 Hz, 3 H). LCMS:m / z [M+H] + = 354 Example 99

[0645] [ka]

[0646] 3-amino-8-(7-fluorobenzo[d]oxazole-5-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 2-amino-4-bromo-6-fluorophenol 8.03 g, 42.35 mmol of tin(II) chloride was added to a 60 mL solution of 4-bromo-2-fluoro-6-nitrophenol (2 g, 8.47 mmol) in ethanol. The reaction solution was heated until refluxed and stirred for 2 hours. The reaction solution was concentrated and added to an aqueous sodium bicarbonate solution. The solution was adjusted to pH 8, extracted with ethyl acetate (50 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was concentrated, and purified by column chromatography to obtain a pale yellow solid (800 mg, 46%). LCMS: m / z [M+H] + = 206.

[0647] Step 2: 5-bromo-7-fluorobenzo[d]oxazole 2-amino-4-bromo-6-fluorophenol (300 mg, 1.46 mmol) and p-toluenesulfonic acid (251 mg, 1.46 mmol) were dissolved in trimethyl orthoformate (6 mL), and the mixture was stirred at 120°C for 3 hours. The reaction solution was concentrated, and the pH was adjusted to 8 by adding aqueous sodium bicarbonate solution. The solution was extracted with ethyl acetate (50 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to obtain the target product (60 mg, 19%), which was a pale yellow solid. LCMS: m / z [M+H] + = 216.

[0648] Step 3: 7-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]oxazole 5-bromo-7-fluorobenzo[d]oxazole (60 mg, 0.28 mmol), bis(pinacolate)diborone (85 mg, 0.34 mmol), potassium acetate (55 mg, 0.56 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane adduct (23 mg, 0.028 mmol) were sequentially added to 1,4-dioxane (4 mL), protected with argon gas, and stirred at 100°C for 16 hours. The reaction solution was used directly in the next step.

[0649] Step 4: To the reaction solution from the previous step, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (62 mg, 0.21 mmol), cesium carbonate (186 mg, 0.57 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct (16 mg, 0.019 mmol), and water (0.5 mL) were added, and the mixture was stirred at 100°C for 5 hours. The reaction solution was filtered, concentrated, and purified by column chromatography to obtain a pale yellow solid (12 mg, 2-step yield: 16%).

[0650] 1 H NMR (400MHz, CHLOROFORM-d) 8.29(s, 1H), 8.19(s, 1H), 7.90(d, J = 10.8 Hz, 1H), 7.78(d, J = 6.4 Hz, 1H), 7.32-7.25 (m, 2H), 6.98-6.87(m, 1H), 5.22-4.81(m, 1H), 3.55-3.31(m, 2H), 1.70-1.63(m, 2H), 0.99(t, J = 7.3 Hz, 3H). LCMS:m / z [M+H] + = 354 Example 100

[0651] [ka]

[0652] 3-amino-8-(6-fluorobenzoxazole-7-yl)-N-propylimidazopyridine-2-carboxamide Step 1: 6-amino-2-bromo-3-fluorophenol 2-Bromo-3-fluoro-6-nitrophenol (1 g, 4.25 mmol) and Raney nickel (0.5 g) were added to 10 mL of methanol and stirred at room temperature under a hydrogen atmosphere for 16 hours. The mixture was filtered, the filtrate was concentrated, and the title product (330 mg, yield: 34%) was obtained by column chromatography (petroleum ether:ethyl acetate = 2:1). LC-MS: m / z [M+H]+ = 206.

[0653] Step 2: 7-bromo-6-fluorobenzoxazole Under nitrogen protection, 6-amino-2-bromo-3-fluorophenol (300 mg, 1.46 mmol) and p-toluenesulfonic acid (25 mg, 0.146 mmol) were added to trimethyl orthoformate (5 ml) and stirred at 80°C for 3 hours. The mixture was concentrated and purified by column chromatography (petroleum ether:ethyl acetate = 3:1) to obtain the title product (270 g, yield 86%), which was a pale yellow solid. LC-MS: m / z [M+H] + = 216.

[0654] Step 3: 3-amino-N-propyl-8-(trimethylstannyl)imidazo[1,2-a]pyridine-2-carboxamide 3-amino-N-propyl-8-bromoimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol), hexamethyldisin (163 mg, 0.5 mmol), and tetrakis(triphenylphosphine)palladium (20 mg) were sequentially added to dioxane (3 mL), and the mixture was stirred at 80°C for 16 hours. Column chromatography yielded the title compound (68 mg, 52%), which was a blue solid. LCMS: m / z[M+H]+=383.

[0655] Step 4: 7-bromo-6-fluorobenzoxazole (40 mg, 0.19 mmol), 3-amino-N-propyl-8-(trimethylstannyl)imidazo[1,2-a]pyridine-2-carboxamide (68 mg, 0.18 mmol), and bis(triphenylphosphine)palladium(II) dichloride (CAS No.: 13965-03-2, 20 mg) were sequentially added to dioxane (5 mL), and the mixture was stirred at 100°C for 16 hours. The mixture was filtered and prepared to obtain the target compound (5 mg, yield: 7%), which was a yellow solid.

[0656] 1HNMR (400 MHz, CDCl3) δ 8.07 (s, 1H), 7.83 (dd, J = 8.7, 4.4 Hz, 2H), 7.35 - 7.28 (m, 2H), 7.01 (d, J = 37.2 Hz, 2H), 4.97 (s, 2H), 3.34 (dd, J = 13.8, 6.7 Hz, 2H), 1.26 (s, 2H), 0.93 (t, J = 7.4 Hz, 3H). LC-MS: m / z [M+H] + = 354.

[0657] Example 101

[0658] [ka]

[0659] 3-amino-8-(6-fluorobenzofuran-7-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 2-Bromo-1-(2,2-dimethoxyethoxy)-3-fluorobenzene 2-Bromo-3-fluorophenol (3g, 15.7 mmol), 2-bromo-1,1-dimethoxyethane (2.66g, 15.7 mmol), and potassium carbonate (4.34g, 31.4 mmol) were sequentially added to N,N-dimethylformamide (30 mL), and the mixture was stirred at 135°C for 1 hour. After adding 150 mL of water, the mixture was extracted with ethyl acetate (150 mL x 2) and concentrated to obtain 2 g of product (45%, yellow solid).

[0660] Step 2: 7-bromo-6-fluorobenzofuran 2-Bromo-1-(2,2-dimethoxyethoxy)-3-fluorobenzene (1 g, 3.58 mmol) and polyphosphate (1.22 g, 3.58 mmol) were dissolved in toluene (20 mL) and stirred at 130 °C for 16 hours. After cooling to room temperature, 100 ml of water was added, and the mixture was extracted with ethyl acetate (100 ml x 2). The mixture was concentrated, and 0.35 g of the product (45%, yellow oily substance) was obtained by column chromatography (petroleum ether).

[0661] Step 3: (6-fluorobenzofuran-7-yl)boronic acid Under the protection of nitrogen gas, butyllithium (0.61 g, 9.6 mmol) was added dropwise to a solution of 7-bromo-6-fluoro-1-benzofuran (0.215 g, 1.0 mmol) in tetrahydrofuran (10 mL) at -70°C. After the addition was complete, the mixture was stirred at this temperature for 1 hour. Trimethylboric acid (0.16 g, 1.5 mmol) was added to the mixture, and stirring was continued for 30 minutes. Sodium hydroxide aqueous solution (2 N, 2 mL) was added to the reaction solution, the pH was adjusted to 2 with hydrochloric acid solution (1 M), and the solution was extracted with ethyl acetate (50 mL x 2) and concentrated to obtain 110 mg of product (61%, yellow solid).

[0662] Step 4: The procedure was the same as in the synthesis example of compound vii, using (6-fluorobenzofuran-7-yl)boronic acid (30 mg, 0.17 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (49 mg, 0.17 mmol) as raw materials to obtain the title product (30 mg, 46%), which was a pale yellow solid.

[0663] 1 H NMR (400 MHz, DMSO-d6) 8.26 (dd, J = 7.0, 0.9 Hz, 1H), 7.96 (d, J = 2.2 Hz, 1H), 7.74 (dd, J = 8.6, 5.2 Hz, 1H), 7.54 (t, J = 6.2 Hz, 1H), 7.29 (dd, J = 10.1, 8.6 Hz, 1H), 7.18 (d, J = 6.0 Hz, 1H), 7.04 (d, J = 2.2 Hz, 1H), 6.96 (d, J = 6.9 Hz, 1H), 6.21 (s, 2H), 3.15 - 3.03 (m, 2H), 1.53 - 1.36 (m, 2H), 0.80 (t, J = 7.4 Hz, 3H). LCMS MS m / z (ESI): 353 [M+1] + .

[0664] Example 102

[0665] [ka]

[0666] (3-amino-8-(6-fluorobenzofuran-7-yl)imidazo[1,2-a]pyridine-2-yl)(3-methylazetidine-1-yl)methanone Step 1: (3-amino-8-bromoimidazo[1,2-a]pyridine-2-yl)(3-methylazetidine-1-yl)methanone The procedure was the same as for the synthesis of intermediate vi (routine 1, step 2), using 3-amino-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid (100 mg, 0.39 mmol) and 3-methylazetidine (41 mg, 0.59 mmol) as raw materials to obtain the target product (105 mg, crude product), which was a yellowish-green solid.

[0667] Step 2: The procedure was the same as in the synthesis example of compound vii, using (3-amino-8-bromoimidazo[1,2-a]pyridine-2-yl)(3-methylazetidine-1-yl)methanone (0.15 g, 0.49 mmol) and (6-fluorobenzofuran-7-yl)boronic acid (0.088 g, 0.49 mmol) as raw materials to obtain the product (20 mg, 11%), which was a yellow solid.

[0668] 1HNMR (400MHz, DMSO-d6) 8.25 (d, J = 6.4 Hz, 1 H), 7.98 (s, 1 H), 7.73 (s, 1 H), 7.33 - 7.20 (m, 2 H), 7.03 (s, 1 H), 6.98 (d, J = 5.9 Hz, 1 H), 6.26 (s, 2 H), 4.37-4.33 (m, 1 H), 4.08-4.04 (m, 1 H), 3.79-3.75 (m, 1 H), 3.52-3.48 (m, 1 H), 2.61-3.57 (m, 1 H), 1.11 (d, J = 5.9 Hz, 3 H). LC-MS: m / z [M+1] + = 365.

[0669] Example 103

[0670] [ka]

[0671] 3-amino-8-(6-methoxybenzofuran-7-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 2-Bromo-1-(2,2-dimethoxyethoxy)-3-methoxybenzene 2-Bromo-3-methoxyphenol (2 g, 10.47 mmol), 2-bromo-1,1-dimethoxyethane (1.95 g, 11.52 mmol), and cesium carbonate (6.82 g, 20.94 mmol) were dissolved in DMF (20 mL) and stirred at 100°C for 15 hours. The reaction solution was diluted with ethyl acetate (50 mL), washed with saturated sodium chloride aqueous solution (20 mL x 3), the organic phase was dried, and concentrated to obtain the title product (2 g, 68%), which was a yellow oily substance.

[0672] Step 2: 7-bromo-6-methoxybenzofuran 2-Bromo-1-(2,2-dimethoxyethoxy)-3-methoxybenzene (500 mg, 1.72 mmol) and polyphosphate (5 g) were added to toluene (100 mL) and stirred at 120°C for 15 hours. The mixture was concentrated, diluted with ethyl acetate (50 mL), washed with saturated sodium chloride aqueous solution (30 mL x 3), the organic phase was dried, concentrated, and purified by column chromatography to obtain the title product (400 mg, crude product), which was a yellow oily substance.

[0673] Step 3: (6-methoxybenzofuran-7-yl)boronic acid 7-Bromo-6-methoxybenzofuran (100 mg, 0.44 mmol) was dissolved in anhydrous tetrahydrofuran (4 mL), cooled to -78°C, and n-butyllithium (0.33 mL, 0.53 mmol) was slowly added dropwise, and the mixture was stirred at -78°C for 30 minutes. A solution of triisopropyl borate (124 mg, 0.66 mmol) in tetrahydrofuran (3 mL) was slowly added dropwise, and the mixture was stirred at -78°C for 1 hour. The reaction solution was quenched with saturated aqueous ammonium chloride (20 mL), extracted with ethyl acetate (30 mL x 3), the organic phase was dried, concentrated, and purified by column chromatography to obtain the title compound (45 mg, 53%), which was a yellow oily substance.

[0674] Step 4: The procedure was the same as in the synthesis example of compound vii, using (6-methoxybenzofuran-7-yl)boronic acid (30 mg, 0.17 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (49 mg, 0.17 mmol) as raw materials to obtain the title product (30 mg, 46%).

[0675] 1H NMR (400 MHz, DMSO-d6) 8.44 (s, 1H), 7.84 (s, 1H), 7.75-7.71 (m, 2H), 7.22 (d, J = 8.6 Hz, 2H), 6.97 (s, 1H), 3.79 (s, 3H), 3.20-3.16 (m, 2H), 1.46 (dd, J = 14.4, 7.2 Hz, 2H), 0.83 (t, J = 7.3 Hz, 3H). LCMS MS m / z (ESI): 365 [M+1].

[0676] Example 104

[0677] [ka]

[0678] 3-amino-8-(4-methoxy-1-methyl-1H-benzo[d][1,2,3]triazole-5-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 4-Bromo-3-methoxy-N-methyl-2-nitroaniline 700 mg of 3-methoxy-N-methyl-2-nitroaniline (3.8 mmol) was dissolved in 40 mL of acetonitrile, and 720 mg of NBS (4.0 mmol) was added. The mixture was stirred at room temperature for 15 minutes. The reaction solution was directly concentrated and purified by column chromatography to obtain the title compound (914 mg, yield: 91%), which was a yellow oily liquid. LC-MS: m / z [M+H] + =261.

[0679] Step 2: 4-bromo-3-methoxy-N 1 -methylbenzene-1,2-diamine 4-Bromo-3-methoxy-N-methyl-2-nitroaniline (914 mg, 3.5 mmol) was dissolved in methanol (30 mL), Raney nickel (250 mg) was added, and the gas in the system was replaced three times with a hydrogen balloon. The mixture was then stirred at room temperature for 2 hours under the protection of the hydrogen balloon. After filtration, the filtrate was concentrated to obtain the title compound (696 mg, yield: 86%), which was a yellow solid. LC-MS: m / z [M+H] + =231.

[0680] Step 3: 5-bromo-4-methoxy-1-methyl-1H-benzo[d][1,2,3]triazole At 0°C, 4-bromo-3-methoxy-N 1 A 0.5 M, 6 mL solution of methylbenzene-1,2-diamine in acetic acid was mixed with a 1.2 M, 5 mL aqueous solution of sodium nitrite. The mixture was stirred at 0°C for 30 minutes. The reaction solution was concentrated and purified by column chromatography to obtain the title compound (365 mg, yield: 50%), which was a yellow solid. LC-MS: m / z [M+H] + = 242.

[0681] Step 4: 4-Methoxy-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d][1,2,3]triazole The experimental procedure was the same as in Example 94 (Step 3), and the title compound (50 mg, 42%) was obtained using 5-bromo-4-methoxy-1-methyl-1H-benzo[d][1,2,3]triazole (100 mg, 0.41 mmol) as the starting material. LC-MS: m / z [M+H] + =290.

[0682] Step 5: Using the same procedure as in the synthesis example of compound vii, 4-methoxy-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d][1,2,3]triazole (50.0 mg, 0.17 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (50 mg, 0.17 mmol) were used as raw materials to obtain the title product (30 mg, 46%).

[0683] 1 H NMR (400 MHz, DMSO) 8.14 (d, J = 6.8 Hz, 1H), 7.66 - 7.45 (m, 3H), 7.06 (d, J = 6.8 Hz, 1H), 6.91 (t, J = 6.9 Hz, 1H), 6.13 (s, 2H), 4.37 (s, 3H), 4.33 (s, 3H), 3.15 (dd, J = 13.9, 6.9 Hz, 2H), 1.45 (dd, J = 14.3, 7.0 Hz, 2H), 0.80 (t, J = 7.4 Hz, 3H).LCMS MS m / z (ESI): 380 [M+1].

[0684] Example 105

[0685] [ka]

[0686] 3-amino-8-(6-fluoro-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-7-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 7-bromo-6-fluorobenzo[d]oxazole-2(3H)-one 6-amino-2-bromo-3-fluorophenol (700 mg, 3.41 mmol) and CDI (719 mg, 4.44 mmol) were added to tetrahydrofuran (25 mL) and stirred at room temperature for 3 hours. The reaction solution was concentrated, and the title compound (600 mg, 75%) was obtained by column chromatography (petroleum ether / ethyl acetate = 3 / 1).

[0687] Step 2: 7-Bromo-6-fluoro-3-methylbenzo[d]oxazole-2(3H)-one 7-Bromo-6-fluorobenzo[d]oxazole-2(3H)-one (600 mg, 2.60 mmol), cesium carbonate (2.54 g, 7.79 mmol), and methyl iodide (443 mg, 3.12 mmol) were sequentially added to DMF (10 mL) and stirred at room temperature for 18 hours. The reaction solution was diluted with water (50 mL), extracted with ethyl acetate (50 mL x 2), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and the title compound (350 mg, 55%) was obtained by column chromatography. LC-MS: m / z [M+H] + = 246.

[0688] Step 3: 6-Fluoro-3-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]oxazole-2(3H)-one The experimental procedure was the same as in Example 94 (Step 3), and the title compound (18 mg, 30%) was obtained using 7-bromo-6-fluoro-3-methylbenzo[d]oxazole-2(3H)-one (50 mg, 0.2 mmol) as the starting material, which was a yellow solid.

[0689] Step 4: The procedure was the same as in the synthesis example of compound vii, using 6-fluoro-3-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]oxazole-2(3H)-one (18 mg, 0.06 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (18 mg, 0.06 mmol) as starting materials to obtain the title product (5 mg, 22%).

[0690] 1 H NMR (400 MHz, DMSO) 7.82 (s, 1H), 7.23 -7.15 (m, 1H), 7.14 - 7.06 (m,2H), 7.01 - 6.95 (m, 1H), 6.91 (s, 1H), 4.92 (s, 2H), 3.45 (s, 3H), 3.35 (dd, J = 13.9, 6.7 Hz, 2H), 1.70 - 1.59 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H). LCMS MS m / z (ESI): 384 [M+1].

[0691] Example 106

[0692] [ka]

[0693] 3-amino-8-(6-fluoro-2,3-dihydrobenzofuran-7-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 1-Bromo-2-(2-bromoethoxy)-4-fluorobenzene Under the protection of argon gas, 2-bromo-5-fluorophenol (10 g, 53.4 mmol), 1,2-dibromoethane (49 g, 262 mmol), and potassium carbonate (8 g, 57.6 mmol) were sequentially added to N,N-dimethylformamide (150 mL), and the mixture was stirred at 60°C for 2 hours. After filtration, water (250 mL) was added to the mother liquor, and the mixture was extracted with ethyl acetate (250 mL x 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain the product (8 g, 51%), which was a colorless liquid.

[0694] 1 H NMR (400 MHz, CDCl3) δ 7.53 - 7.44 (m, 1H), 6.67 - 6.58 (m, 2H), 4.30 (t, J = 6.4 Hz, 2H), 3.69 (t, J = 6.4 Hz, 2H).

[0695] Step 2: 6-fluoro-2,3-dihydro-1-benzofuran Under the protection of argon gas, 1-bromo-2-(2-bromoethoxy)-4-fluorobenzene (1 g, 3.36 mmol) was dissolved in anhydrous tetrahydrofuran (30 mL), the mixture was cooled to -78°C, and a solution of n-butyllithium in tetrahydrofuran (1 M, 3.7 mL) was slowly added dropwise, stirring at -78°C for 3 hours. The temperature was raised to 0°C and stirred for 1 hour. A portion of the reaction solution was taken, concentrated, and subjected to NMR analysis. The residual reaction solution was used directly in the next step.

[0696] 1 H NMR (400 MHz, CDCl3) δ 7.13 - 7.08 (m, 1H), 6.61 - 6.50 (m, 2H), 4.62 (t, J = 8.7 Hz, 2H), 3.17 (t, J = 8.7 Hz, 2H).

[0697] Step 3: (6-fluoro-2,3-dihydrobenzofuran-7-yl)boronic acid Under the protection of argon gas, a solution of 6-fluoro-2,3-dihydro-1-benzofuran (0.4 g, 2.9 mmol) in anhydrous tetrahydrofuran (30 mL) was cooled to -78°C. A solution of lithium diisopropylamide in tetrahydrofuran (2 M, 2.2 mL) was added dropwise, and the mixture was stirred for 10 minutes. Then, a solution of trimethyl borate (0.33 g, 3.19 mmol) in tetrahydrofuran (10 mL) was added dropwise to the reaction solution, and the mixture was stirred for 10 minutes while maintaining the temperature at -78°C. The mixture was quenched with 1 M aqueous hydrochloric acid, extracted with ethyl acetate (20 ml x 3), concentrated the organic phase, and washed with diethyl ether to obtain a white solid (0.49 g, 93%).

[0698] 1HNMR (400 MHz, CDCl3) δ 7.24 (t, J = 7.0 Hz, 1H), 6.60 (dd, J = 10.4, 8.4 Hz, 1H), 5.98-5.94 (m, 2H), 4.74 (t, J = 8.7 Hz, 2H), 3.21 (t, J = 8.7Hz, 2H).

[0699] Step 4: The procedure was the same as in the synthesis example of compound vii, using 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (6-fluoro-2,3-dihydro-1-benzofuran-7-yl)boronic acid (124 mg, 0.68 mmol) as raw materials to obtain the target product (25 mg, 20%), which was a yellow solid.

[0700] 1 H NMR (400 MHz, DMSO-d6) δ 8.16 (d, J = 6.4 Hz, 1H), 7.58 (d, J = 5.5 Hz, 1H), 7.29 - 7.21 (m, 1H), 6.99 (d, J = 6.2 Hz, 1H), 6.88 (t, J = 6.7 Hz, 1H), 6.74 (t, J = 9.0 Hz, 1H), 6.15 (s, 2H), 4.53 (s, 2H), 3.19 (dd, J = 19.1, 8.0 Hz, 4H), 1.47 (dd, J = 14.2, 7.1 Hz, 2H), 0.82 (t, J = 7.1 Hz, 3H). LCMS: m / z [M+H] + = 355.

[0701] Example 107

[0702] [ka]

[0703] 3-amino-8-(7-fluoro-2-methoxynaphthalene-1-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 8-Bromo-7-methoxy-3,4-dihydronaphthalene-1(2H)-one 7-Methoxy-3,4-dihydronaphthalene-1(2H)-one (10.0 g, 56.82 mmol) was added to acetonitrile (150 mL), and NBS (10.1 g, 57.38 mmol) was added. The mixture was stirred at room temperature for 5 hours. Sodium sulfite solution was added to the reaction solution to quench it, and the reaction solution was concentrated. The title compound (7.4 g, 51%) was obtained by column chromatography (petroleum ether / ethyl acetate = 10 / 1).

[0704] 1 H NMR (400 MHz, CDCl3) δ 7.20 - 7.14 (m, 1H), 7.01 (dd, J = 8.4, 1.8 Hz, 1H), 3.90 (d, J = 2.7 Hz, 3H), 2.93 - 2.85 (m, 2H), 2.76 - 2.61 (m, 2H), 2.17 - 1.95 (m, 2H).

[0705] Step 2: 8-Bromo-2-fluoro-7-methoxy-3,4-dihydronaphthalene-1(2H)-one 8-Bromo-7-methoxy-3,4-dihydronaphthalene-1(2H)-one (1.0 g, 3.95 mmol) was added to methanol (15 mL), and 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octanbis(tetrafluoroborate) (1.7 g, 4.74 mmol) was added. The mixture was stirred overnight at room temperature. The reaction solution was concentrated and purified by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain the title compound (850 mg, 79%).

[0706] 1 H NMR (400 MHz, DMSO-d6) 7.37-7.33 (m, 2H), 5.68 - 5.04 (m, 1H), 3.87 (s, 3H), 3.19 - 2.99 (m, 2H), 2.49 - 2.11 (m, 2H).

[0707] Step 3: 8-Bromo-2-fluoro-7-methoxy-1,2,3,4-tetrahydronaphthalene-1-ol 8-Bromo-2-fluoro-7-methoxy-3,4-dihydronaphthalene-1(2H)-one (750 mg, 2.75 mmol) was added to methanol (10 mL). The mixture was cooled to 0°C, sodium borohydride (125 mg, 3.29 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction solution was quenched with water, filtered, concentrated, and the title compound (600 mg, 79%) was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1).

[0708] 1 H NMR (400 MHz, DMSO-d6) 7.12 (d, J = 8.5 Hz, 1H), 7.03 (d, J = 8.5 Hz, 1H), 5.41 (d, J = 5.9 Hz, 1H), 5.02 - 4.86 (m, 1H), 4.73 (ddt, J = 47.4, 12.4, 3.7 Hz, 1H), 3.81 (s, 3H), 2.83 (tdd, J = 17.2, 14.6, 5.3 Hz, 2H), 2.29 - 2.10 (m, 1H), 1.86 (d, J = 3.9 Hz, 1H).

[0709] Step 4: 5-bromo-3-fluoro-6-methoxy-1,2-dihydronaphthalene 8-Bromo-2-fluoro-7-methoxy-1,2,3,4-tetrahydronaphthalene-1-ol (600 mg, 2.18 mmol) was added to toluene (10 mL), and p-toluenesulfonic acid (80 mg, 0.44 mmol) was added. The mixture was stirred at 50°C for 3 hours. The reaction solution was concentrated and purified by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain the title compound (520 mg, 92%).

[0710] 1H NMR (400 MHz, DMSO-d6) 7.14 (t, J = 7.8 Hz, 1H), 6.89 - 6.78 (m, 1H), 6.42 (d, J = 14.3 Hz, 1H), 3.80 (s, 3H), 2.96 (dt, J = 8.4, 4.1 Hz, 2H), 2.55 (td, J = 8.3, 4.5 Hz, 2H).

[0711] Step 5: 1-Bromo-7-fluoro-2-methoxynaphthalene 5-Bromo-3-fluoro-6-methoxy-1,2-dihydronaphthalene (520 mg, 2.04 mmol) was added to dichloromethane, and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ, 551 mg, 2.42 mmol) was added. The mixture was stirred at 40°C for 3 hours, the reaction solution was concentrated, and the title compound (470 mg, 91%) was obtained by column chromatography (petroleum ether / ethyl acetate = 10 / 1).

[0712] 1 H NMR (400 MHz, DMSO-d6) δ 8.14 - 7.99 (m, 2H), 7.71 (dd, J = 11.7, 9.8 Hz, 1H), 7.54 (dd, J = 18.6, 9.0 Hz, 1H), 7.40 - 7.25 (m, 1H), 4.01 (s, 3H).

[0713] Step 6: 2-(7-fluoro-2-methoxynaphthalene-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane The experimental procedure was the same as in Example 94 (Step 3), using 1-bromo-7-fluoro-2-methoxynaphthalene (470 mg, 1.84 mmol) as the starting material, and the title compound (350 mg, 62%) was obtained by column chromatography (petroleum ether / ethyl acetate = 5 / 1).

[0714] 1H NMR (400 MHz, CD3OD) 7.88 (t, J = 8.0 Hz, 1H), 7.80 - 7.68 (m, 1H), 7.54 - 7.39 (m, 1H), 7.25 (dd, J = 15.1, 6.0 Hz, 1H), 7.04 (td, J = 8.7, 2.5 Hz, 1H), 3.83 (d, J = 4.7 Hz, 3H), 1.37 (s, 12H).

[0715] Step 7: The procedure was the same as in the synthesis example of compound vii, using 2-(7-fluoro-2-methoxynaphthalene-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (80 mg, 0.26 mmol) and 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (70 mg, 0.24 mmol) as raw materials to obtain the title compound (5 mg, 4%) as the product.

[0716] 1 H NMR (400 MHz, CD3OD) 8.17-8.16 (d, J=4.0 Hz, 1H), 8.09-8.07 (d, J = 8.0Hz, 1H), 7.97-7.94 (m, 1H), 7.54-7.52 (d, J = 8.0Hz, 1H), 7.18-7.14 (t, 1H), 7.09-7.02 (m, 2 H), 6.89-6.86 (d, J = 12.0 Hz, 1H), 3.86 (s, 3 H), 3.25-3.22 (t, 2H), 1.56-1.47 (m, 2 H), 0.92-0.88 (t, 3H). LCMS: LC-MS:m / z [M+H] + = 393.

[0717] Example 108

[0718] [ka]

[0719] 3-amino-8-(2-fluoro-7-methoxynaphthalene-1-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 2-Fluoro-7-methoxy-3,4-dihydronaphthalene-1-yltrifluoromethanesulfonate Under the protection of nitrogen gas, 2-fluoro-7-methoxy-3,4-dihydronaphthalene-1(2H)-one (200 mg, 1.03 mmol) was dissolved in 10 ml of anhydrous tetrahydrofuran. The solution was cooled to -78°C in a dry ice acetone bath, and LiHMDS (1 M, 2.1 ml) was slowly added at this temperature. After maintaining this temperature and reacting for 1 hour, PhNTf2 (736 mg, 2.06 mmol) was dissolved in anhydrous tetrahydrofuran (2 ml) and slowly added dropwise. The temperature was raised to room temperature, and the reaction was continued for 16 hours. After the reaction was complete, the solution was poured into 100 ml of water, extracted with ethyl acetate (100 ml x 3), concentrated, and obtained the title compound (150 mg, yellow oily substance) by column chromatography (petroleum ether / ethyl acetate = 95 / 5) with a yield of 44.7%. LCMS MS m / z (ESI): 327 [M+1]. Step 2: 2-Fluoro-7-methoxynaphthalene-1-yltrifluoromethanesulfonate Under the protection of nitrogen gas, 2-fluoro-7-methoxy-3,4-dihydronaphthalene-1-yltrifluoromethanesulfonate (2000 mg, 6.13 mmol) and 2,3-dichloro-5,6-dicyano-p-benzoquinone (2785 mg, 12.27 mmol) were dissolved in toluene and reacted at 70°C for 16 hours. After the reaction, 100 mL of water was added, and the mixture was extracted with ethyl acetate (100 mL x 3). The organic phase was rotated dry, and the title compound (1500 mg, yellow oily liquid) was obtained by column chromatography (petroleum ether / ethyl acetate = 95 / 5) with a yield of 75.5%. LCMS MS m / z (ESI): 325 [M+1].

[0720] Step 3: 2-Fluoro-7-methoxynaphthalene-1-yltrifluoromethanesulfonate (20 mg, 0.06 mmol), 3-amino-8-(trimethylstannyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide (23 mg, 0.06 mmol), and Pd(PPh3)4 (14 mg, 0.012 mmol) were sequentially added to DMF (1 mL), and the mixture was reacted by microwave at 120°C for 2 hours. The reaction solution was diluted with ethyl acetate (20 mL), washed with saturated sodium chloride aqueous solution (10 mL x 3), the organic phase was dried, concentrated, and the title product (2 mg, 8%) was obtained by column chromatography, which was a yellow solid.

[0721] 1 H NMR (400 MHz, CDCl3) 8.29 (s, 1H), 7.90 (s, 1H), 7.78 (d, J = 9.0 Hz, 1H), 7.69 - 7.43 (m, 2H), 7.24 (s, 2H), 7.10 (d, J = 7.9 Hz, 1H), 6.86 (s, 1H), 3.71 (d, J = 26.3 Hz, 3H), 3.22 (s, 2H), 1.57 - 1.51 (m, 2H), 0.87 (t, J = 7.1 Hz, 3H). LCMS MS m / z (ESI): 393 [M+1].

[0722] Example 109

[0723] [ka]

[0724] 3-amino-8-(6-methoxyquinoline-5-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 5-Bromo-6-Methoxyquinoline 6-Methoxyquinoline (2.0 g, 12.6 mmol) was added to acetonitrile (20 mL), and NBS (2.24 g, 12.6 mmol) was added in batches. The mixture was stirred at room temperature for 16 hours. The mixture was poured into water (50 mL), extracted with ethyl acetate (50 mL x 3), and purified by column chromatography to obtain a gray solid (1 g, 33%). LC-MS: m / z [M+H] + = 238.

[0725] Step 2: 5-bromo-6-methoxyquinoline (100 mg, 0.42 mmol) was dispersed in dioxane (2 mL), and 3-amino-N-propyl-8-(trimethyltin)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.26 mmol) and Pd(PPh3)2Cl2 (15 mg, 0.021 mmol) were added sequentially. The mixture was then purged with nitrogen gas, the tube was sealed, and the mixture was stirred at 100°C for 18 hours. The target product (6 mg, 6%) was obtained by column chromatography.

[0726] 1 H NMR (400 MHz, DMSO) 8.75 (d, J = 2.8 Hz, 1H), 8.28 - 8.18 (m, 1H), 8.14 (d, J = 9.4 Hz, 1H), 7.81 (d, J = 9.4 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 6.1 Hz, 1H), 7.34 (dd, J = 8.5, 4.1 Hz, 1H), 6.96 (d, J = 3.3 Hz, 2H), 6.19 (s, 2H), 3.82 (s, 3H), 3.08 (dd, J = 11.8, 5.9 Hz, 2H), 1.38 (dd, J = 14.6, 7.2 Hz, 2H), 0.75 (t, J = 7.4 Hz, 3H). LC-MS: m / z [M+H] + =376.

[0727] Example 110

[0728] [ka]

[0729] 3-amino-7-fluoro-8-(5-fluoro-2-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol), (5-fluoro-2-methoxyphenyl)boronic acid (115 mg, 0.68 mmol), cesium carbonate (221 mg, 0.68 mmol), and (2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate (SPhos-Pd-G3, CAS number: 1445085-82-4, 31 mg, 0.04 mmol) were sequentially added to a mixture of dioxane and water (2 mL / 0.4 mL), protected with argon gas, and stirred at 100°C for 2 hours. 20 mL of water was added, and the mixture was extracted with dichloromethane (20 mL x 3). The organic phase was concentrated, and the target product (74 mg, 65%) was obtained by column chromatography (petroleum ether:ethyl acetate = 1:1 to 1:5), which was a yellow solid.

[0730] 1 H NMR (400MHz, DMSO-d6) 8.23-8.19 (m, 1 H), 7.59 (br. s., 1 H), 7.29-7.25 (m, 2 H), 7.16 (br. s., 1 H), 7.01 (br. s., 1 H), 6.17 (s, 2 H), 3.71 (s, 3 H), 3.17-3.13 (m, 2 H), 1.48-1.44 (m, 2 H), 0.83-0.79 (m, 3 H). LC-MS: m / z [M+H] + = 361.

[0731] Example 111

[0732] [ka]

[0733] 3-amino-8-(2,5-dimethylphenyl)-7-fluoro-N-propylimidazo[1,2-a]pyridine-2-carboxamide[1,2-a] The procedure was the same as the synthesis method in Example 110, using 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (2,5-dimethoxyphenyl)boronic acid (124 mg, 0.68 mmol) as raw materials to obtain the target product (67 mg, 57%), which was a yellow solid.

[0734] 1 H NMR (400MHz, DMSO-d6) 8.20 (br. s., 1 H), 7.58 (br. s., 1 H), 7.07 (d, J = 8.3 Hz, 1 H), 7.03 - 6.92 (m, 3 H), 6.16 (br. s., 2 H), 3.72 (s, 3 H), 3.66 (s, 3 H), 3.20 - 3.11 (m, 2 H), 1.46 (d, J = 6.4 Hz, 2 H), 0.84 - 0.78 (m, 3 H). LC-MS: m / z [M+H] + = 373.

[0735] Example 112

[0736] [ka]

[0737] 3-amino-7-fluoro-8-(2-fluoropyridine-3-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as the synthesis method in Example 110, using 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (2-fluoropyridine-3-yl)boronic acid (96 mg, 0.68 mmol) as raw materials to obtain the target product (70 mg, 67%), which was a yellow solid.

[0738] 1 H NMR (400MHz, DMSO-d6) 8.37 (t, J = 6.4 Hz, 1 H), 8.34 - 8.21 (m, 2 H), 7.65 (br. s., 1 H), 7.54 (br. s., 1 H), 7.10 (br. s., 1 H), 6.24 (s, 2 H), 3.16 (d, J = 5.9 Hz, 2 H), 1.52 - 1.39 (m, 2 H), 0.85 - 0.79 (m, 3 H). LC-MS: m / z [M+H] + =332.

[0739] Example 113

[0740] [ka]

[0741] 3-amino-8-(3,5-difluorophenyl)-7-fluoro-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as the synthesis method in Example 110, using 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (3,5-difluorophenyl)boronic acid (107 mg, 0.68 mmol) as raw materials to obtain the target product (59 mg, 53%), which was a yellow solid.

[0742] 1H NMR (400MHz, DMSO-d6) 8.2(br. s., 1 H), 7.72 (br. s., 1 H), 7.52 (d, J = 6.4 Hz, 2 H), 7.32 (br. s., 1 H), 7.06 (br. s., 1 H), 6.23 (br. s., 2 H), 3.19 (d, J = 5.9 Hz, 2 H), 1.54 - 1.44 (m, 2 H), 0.87 - 0.81 (m, 3 H). LC-MS: m / z [M+H] + = 349.

[0743] Example 114

[0744] [ka]

[0745] 3-amino-7-fluoro-8-(4-methoxypyridine-3-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as the synthesis method in Example 110, using 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (4-methoxypyridine-3-yl)boronic acid (104 mg, 0.68 mmol) as raw materials to obtain the target product (69 mg, 63%), which was a yellow solid.

[0746] 1 H NMR (400MHz, DMSO-d6) 8.53 (br. s., 1 H), 8.44 (br. s., 1 H), 8.24 (br. s., 1 H), 7.59 (br. s., 1 H), 7.22 (br. s., 1 H), 7.03 (br. s., 1 LC-MS: m / z [M+H] += 344.

[0747] Example 115

[0748] [ka]

[0749] 3-amino-7-fluoro-8-(2-methoxypyridine-3-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as the synthesis method in Example 110, using 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (2-methoxypyridine-3-yl)boronic acid (104 mg, 0.68 mmol) as raw materials to obtain the target product (27 mg, 25%), which was a yellow solid.

[0750] 1 H NMR (400MHz, DMSO-d6) 8.36 - 8.14 (m, 2 H), 7.84 (d, J = 7.3 Hz, 1 H), 7.58 (br. s., 1 H), 7.14 (t, J = 5.6 Hz, 1 H), 7.02 (t, J = 7.6 Hz, 1 LC-MS: m / z [M+H] + = 344.

[0751] Example 116

[0752] [ka]

[0753] 3-amino-7-fluoro-8-(3-fluoro-2-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as the synthesis method in Example 110, using 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (3-fluoro-2-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) as raw materials to obtain the target product (37 mg, 32%), which was a yellow solid.

[0754] 1 H NMR (400MHz, DMSO-d6) 8.27 (t, J = 6.6 Hz, 1 H), 7.57 (t, J = 5.6 Hz, 1 H), 7.30 - 7.21 (m, 2 H), 7.16 - 7.09 (m, 1 H), 7.06 (t, J = 7.8 Hz, 1 LC-MS: m / z [M+H] + = 361.

[0755] Example 117

[0756] [ka]

[0757] 3-amino-8-(3,6-dimethoxypyridazin-4-yl)-7-fluoro-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as the synthesis method in Example 110, using 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (3,6-dimethoxypyridazine-4-yl)boronic acid (125 mg, 0.68 mmol) as raw materials to obtain the target product (41 mg, 35%), which was a yellow solid.

[0758] 1 HNMR (400MHz, DMSO-d6) 8.31 (br. s., 1 H), 7.74 (br. s., 1 H), 7.44 (br. s., 1 H), 7.07 (br. s., 1 H), 6.23 (br. s., 2 H), 4.00 (s, 3 H), 3.92 (s, 3 H), 3.18 - 3.08 (m, 2 H), 1.44 (d, J = 6.8 Hz, 2 H), 0.83 - 0.77 (m, 3 H). LC-MS: m / z [M+H] + = 375.

[0759] Example 118

[0760] [ka]

[0761] 3-amino-8-(2-cyano-6-methoxyphenyl)-7-fluoro-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as the synthesis method in Example 110, using 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and 2-(5,5-dimethyl-1,3,2-diboran-2-yl)-3-methoxybenzonitrile (167 mg, 0.68 mmol) as raw materials to obtain the target product (9 mg, 8%), which was a yellow solid.

[0762] 1H NMR (400MHz, DMSO-d6) 8.34-8.30 (m, 1 H), 7.67 (br. s., 1 H), 7.57 (d, J = 7.3 Hz, 3 H), 7.12-7.08 (m, 1 H), 6.23 (s, 2 H), 3.77 (s, 3 H), 3.17-3.13 (m, 2 H), 1.52 - 1.41 (m, 2 H), 0.81 (br. s., 3 H). LC-MS: m / z [M+H] + = 368.

[0763] Example 119

[0764] [ka]

[0765] 3-amino-7-fluoro-8-isobutyl-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as the synthesis method in Example 110, using 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (2-methylpropyl)boronic acid (173 mg, 1.7 mmol) as raw materials to obtain the target product (32 mg, 34%), which was a yellow solid.

[0766] 1 H NMR (400MHz, DMSO-d6) 8.05 (t, J = 6.6 Hz, 1 H), 7.71 (t, J = 5.9 Hz, 1 H), 6.89 (t, J = 7.8 Hz, 1 H), 6.09 (s, 2 H), 3.22 (q, J = 6.7 Hz, 2 H), 2.70 (d, J = 6.8 Hz, 2 H), 2.28 - 2.08 (m, 1 H), 1.60 - 1.44 (m, 2 H), 0.93 - 0.84 (m, 9 H). LC-MS: m / z [M+H] + = 293.

[0767] Example 120

[0768] [ka]

[0769] 3-amino-8-(2,4-dimethoxypyrimidine-5-yl)-7-fluoro-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as the synthesis method in Example 110, using 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (2,4-dimethoxypyrimidine-5-yl)boronic acid (125 mg, 0.68 mmol) as raw materials to obtain the target product (83 mg, 70%), which was a yellow solid.

[0770] 1 H NMR (400MHz, DMSO-d6) 8.48 (t, J = 6.6 Hz, 1 H), 8.26-8.22 (m, 1 H), 7.71-7.67 (m, 1 H), 7.04 (t, J = 7.6 Hz, 1 H), 6.19 (s, 2 H), 3.98 (s, LC-MS: m / z [M+H] + = 375.

[0771] Example 121

[0772] [ka]

[0773] 3-amino-7-fluoro-8-(4-fluoro-2-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as the synthesis method in Example 110, using 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (4-fluoro-2-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) as raw materials to obtain the target product (45 mg, 39%), which was a yellow solid.

[0774] 1 H NMR (400MHz, DMSO-d6) 8.19 (br. s., 1 H), 7.54 (br. s., 1 H), 7.39 (br. s., 1 H), 7.05 (br. s., 1 H), 6.98 (br. s., 1 H), 6.87 (br. s., 1 LC-MS: m / z [M+H] + = 361.

[0775] Example 122

[0776] [ka]

[0777] 3-amino-7-fluoro-8-(2-fluoro-6-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as that used for the synthesis of compound vii. Using 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) as raw materials, the target product (64 mg, 56%) was obtained, which was a yellow solid.

[0778] 1HNMR (400MHz, DMSO-d6) 8.27 (br. s., 1 H), 7.61 (br. s., 1 H), 7.50 (br. s., 1 H), 7.04 (br. s., 2 H), 6.97 (br. s., 1 H), 6.20 (br. s., 2 LC-MS: m / z [M+H] + = 361.

[0779] Example 123

[0780] [ka]

[0781] 3-amino-7-fluoro-8-(6-methoxy-4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 6-Methoxy-2H-benzo[b][1,4]oxazine-3(4H)-one 2-amino-4-methoxyphenol (10.0 g, 71 mmol) was added to acetonitrile (500 ml), followed by chloroacetyl chloride (9.8 g, 86 mmol), and then cesium carbonate (58.4 g, 179 mmol). The mixture was stirred at 80°C for 16 hours, filtered, and the filtrate was rotate-dried. Purification by column chromatography (petroleum ether:ethyl acetate = 1:1) yielded the title compound (9.4 g, 74%), which was a red solid. LC-MS: m / z [M+H] + = 180.

[0782] Step 2: 7-Bromo-6-methoxy-2H-benzo[b][1,4]oxazine-3(4H)-one 6-Methoxy-2H-benzo[b][1,4]oxazine-3(4H)-one (10 g, 55.8 mmol) was dissolved in DMF (100 ml). NBS (10 g, 55.8 mmol) was added at 0°C. After the addition was complete, the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into ice water (500 mL), filtered, and the resulting solid was washed with water (50 mL x 3). The resulting solid was vacuum-dried to obtain the title compound (9 g, 63%), which was a red solid. LC-MS: m / z [M+H] + = 258.

[0783] Step 3: 7-Bromo-6-methoxy-4-methyl-2H-benzo[b][1,4]oxazine-3(4H)-one 7-Bromo-6-methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one (10 g, 38.7 mmol), cesium carbonate (37.2 g, 116 mmol), and methyl iodide (4.17 g, 29.4 mmol) were added in batches to acetonitrile (100 ml), stirred at 35°C for 16 hours, and the reaction solution was poured into ice water (200 mL). The solution was extracted with ethyl acetate (300 mL x 3), concentrated, and purified by column chromatography (petroleum ether:ethyl acetate = 2:1) to obtain the title compound (6 g, 57%), which was an off-white solid. LC-MS: m / z [M+H] + = 272.

[0784] Step 4: 6-Methoxy-4-methyl-7-(tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-1,4-benzoxazine-3-one 7-Bromo-6-methoxy-4-methyl-2H-benzo[b][1,4]oxazine-3(4H)-one (1.04 g, 3.85 mmol), bis(pinacolate)diborone (1.47 g, 5.78 mmol), potassium acetate (754 mg, 7.7 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane adduct (314 mg, 0.39 mmol) were sequentially added to dioxane (30 mL), protected with argon gas, and stirred at 100°C for 16 hours. The mixture was concentrated and purified by column chromatography (petroleum ether:ethyl acetate = 1:1) to obtain the target product (500 mg, 41%), which was a white solid. LC-MS: m / z [M+H] + =320.

[0785] Step 5: The procedure was the same as in the synthesis example of compound vii, using 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and 6-methoxy-4-methyl-7-(tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-1,4-benzoxazin-3-one (217 mg, 0.68 mmol) as raw materials to obtain the target product (12 mg, 9%), which was a yellow solid.

[0786] 1 HNMR (400MHz, DMSO-d6) 8.19 (t, J = 6.4 Hz, 1 H), 7.57 (t, J = 4.9 Hz, 1 H), 7.05 - 6.96 (m, 2 H), 6.92 (s, 1 H), 6.15 (br. s., 2 H), 4.64 (s, LC-MS: m / z [M+H] + = 428.

[0787] Example 124

[0788] [ka]

[0789] 3-amino-N-butyl-7-fluoro-8-(2-fluoro-6-methoxyphenyl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as the synthesis method in Example 110, using 3-amino-7-fluoro-8-bromo-N-butylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) as raw materials to obtain the target product (26 mg, 23%), which was a yellow solid.

[0790] 1 H NMR (400MHz, DMSO-d6) 8.27 (t, J = 6.6 Hz, 1 H), 7.58 (t, J = 5.6 Hz, 1 H), 7.49 (q, J = 7.8 Hz, 1 H), 7.08 - 7.00 (m, 2 H), 6.96 (t, J = 8.8 Hz, 1 H), 6.19 (s, 2 H), 3.74 (s, 3 H), 3.19 (q, J = 6.4 Hz, 2 H), 1.43 (td, J = 7.0, 14.4 Hz, 2 H), 1.23 (t, J = 7.1 Hz, 2 H), 0.85 (t, J = 7.1 Hz, 3 H).LC-MS: m / z [M+H] + = 375.

[0791] Example 125

[0792] [ka]

[0793] 3-amino-7-fluoro-8-(2-fluoro-6-methoxyphenyl)-N-(3,3,3-trifluoropropyl)propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as the synthesis method in Example 110, using 3-amino-7-fluoro-8-bromo-N-(3,3,3-trifluoropropyl)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) as raw materials to obtain the target product (69 mg, 61%), which was a yellow solid.

[0794] 1 H NMR (400MHz, DMSO-d6) 8.27 (t, J = 6.6 Hz, 1 H), 7.79 (t, J = 5.6 Hz, 1 H), 7.56 - 7.43 (m, 1 H), 7.07 - 6.99 (m, 2 H), 6.95 (t, J = 8.6 Hz, 1 LC-MS: m / z [M+H] + = 415.

[0795] Example 126

[0796] [ka]

[0797] 3-amino-8-(3-cyanophenyl)-7-fluoro-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as that used for the synthesis of compound vii. Using 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (3-cyanophenyl)boronic acid (100 mg, 0.68 mmol) as raw materials, the target product (58 mg, 54%) was obtained, which was a yellow solid.

[0798] 1H NMR (400MHz, DMSO-d6) 8.27 (t, J = 6.1 Hz, 1 H), 8.20 (br. s., 1 H), 8.12 (d, J = 7.3 Hz, 1 H), 7.92 (d, J = 7.8 Hz, 1 H), 7.76 - 7.67 (m, 2 LC-MS: m / z [M+H] + = 338.

[0799] Example 127

[0800] [ka]

[0801] 3-amino-8-(3-methoxy-5-fluorophenyl)-7-fluoro-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as that used for the synthesis of compound vii. Using 3-amino-7-fluoro-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (3-cyano-5-fluorophenyl)boronic acid (112 mg, 0.68 mmol) as raw materials, the target product (52 mg, 46%) was obtained, which was a yellow solid.

[0802] 1H NMR (400MHz, DMSO-d6) 8.29 (t, J = 5.9 Hz, 1 H), 8.14 - 8.03 (m, 2 H), 7.96 (d, J = 8.3 Hz, 1 H), 7.76 (br. s., 1 H), 7.11 (t, J = 8.1 Hz, 1 LC-MS: m / z [M+H] + = 356.

[0803] Example 128

[0804] [ka]

[0805] 3-amino-7-(difluoromethyl)-8-(2-fluoro-6-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-Bromo-2-chloro-4-(difluoromethyl)pyridine 3-Bromo-2-chloroisonicotinaldehyde (5g, 22.8 mmol) was dissolved in dichloromethane (50 mL), and diethylaminosulfur trifluoride (DAST, CAS No.: 38078-09-0, 3.67 g, 22.8 mmol) was added dropwise under ice bath. After the addition was complete, the reaction solution was stirred at room temperature for 16 hours, and the reaction solution was quenched with saturated ammonium chloride (20 mL) and separated. The aqueous phase was extracted with dichloromethane (50 mL x 2), the organic phase was combined, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (petroleum ether:ethyl acetate = 2:1) to obtain the target compound (4.3 g, 78.2%). LC-MS: m / z [M+H] + = 242.

[0806] Step 2: 3-Bromo-4-(difluoromethyl)-N-(4-methoxybenzyl)pyridine-2-amine 3-Bromo-2-chloro-4-(difluoromethyl)pyridine (4.1 g, 16.9 mmol) was dissolved in DMF (40 mL), and p-methoxybenzylamine (3.02 g, 22.0 mmol) and potassium carbonate (7.01 g, 50.7 mmol) were added sequentially, and the mixture was stirred at 120 °C for 16 hours. Water (50 mL) was added to the reaction solution to quench it, and the mixture was separated. The aqueous phase was extracted with ethyl acetate (50 mL x 3), and the organic phase was combined. The mixture was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography (petroleum ether:ethyl acetate = 5:1) to obtain the target compound (3.2 g, 55%). LC-MS: m / z [M+H] + =343.

[0807] Step 3: 3-Bromo-4-(difluoromethyl)pyridine-2-amine 3-Bromo-4-(difluoromethyl)-N-(4-methoxybenzyl)pyridine-2-amine (3.1 g, 9.03 mmol) was dissolved in trifluoroacetic acid (30 mL) and stirred at 80°C for 2 hours. The reaction solution was concentrated, and water (20 mL) and saturated sodium bicarbonate solution (10 mL) were added to adjust the pH to 8. The aqueous phase was extracted with ethyl acetate (50 mL x 3), the organic phase was combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography (petroleum ether:ethyl acetate = 5:1) to obtain the target compound (1.1 g, 54.6%). LC-MS: m / z [M+H] + =223.

[0808] Step 4: 3-amino-7-(difluoromethyl)-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as that for the synthesis of intermediate iv (route 1) and intermediate vi (route 1), using 3-bromo-4-(difluoromethyl)pyridine-2-amine as the starting material to obtain the target product, which was a gray solid.

[0809] Step 5: The procedure was the same as the synthesis method in Example 110, using 3-amino-7-(difluoromethyl)-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.32 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) as raw materials to obtain the target product (31 mg, 27%), which was a yellow solid.

[0810] 1 H NMR (400MHz, DMSO-d6) 8.35 (d, J = 2.0 Hz, 1 H), 7.63 (br.s., 1 H), 7.53 (q, J = 7.8 Hz, 1 H), 7.10 - 6.95 (m, 3 H), 6.60-6.28 (m, 3 H), 3.72 (s, 3 H), 3.18-3.14 (m, 2 H), 1.49-1.43 (m, 2 H), 0.85-0.77 (m, 3 H). LC-MS: m / z [M+H] + = 393.

[0811] Example 129

[0812] [ka]

[0813] 3-amino-8-(2-fluoro-6-methoxyphenyl)-7-methoxy-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-7-methoxy-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxylic acid 3-amino-7-fluoro-8-bromoimidazo[1,2-a]pyridine-2-carboxylate ethyl (1.3 g, 4.59 mmol) and sodium hydroxide aqueous solution (4N, 5 mL) were sequentially added to MeOH (30 mL), and the mixture was stirred at 60°C for 16 hours. The pH was neutralized to 6 with 1 M dilute hydrochloric acid, methanol was evaporated, the mixture was filtered, and the cake was dried. The cake was dissolved in N,N-dimethylformamide (10 mL), and HATU (CAS number: 148893-10-1, 1.5 g, 3.96 mmol), n-propylamine (383 mg, 6.6 mmol), and triethylamine (660 mg, 6.6 mmol) were sequentially added, and the mixture was stirred for 16 hours. The reaction solution was poured into water, extracted with dichloromethane (50 mL x 3), dried over anhydrous sodium sulfate, concentrated, and obtained the target product (200 mg, 13%) by column chromatography, which was a gray solid. LC-MS: m / z [M+H] + = 327.

[0814] Step 2: The procedure was the same as the synthesis method of Example 110, using 3-amino-7-methoxy-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (105 mg, 0.32 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) as raw materials to obtain the target product (24 mg, 21%), which was a yellow solid.

[0815] 1 H NMR (400MHz, DMSO-d6) 8.19 (d, J = 7.8 Hz, 1 H), 7.45 - 7.36 (m, 2 H), 7.06 (d, J = 7.3 Hz, 1 H), 6.94 (d, J = 8.3 Hz, 1 H), 6.87 (t, J = 8.3 Hz, 1 H), 6.02 (br. s., 2 H), 3.76 (s, 3 H), 3.69 (s, 3 H), 3.14 (d, J = 6.4 Hz, 2 H), 1.49 - 1.40 (m, 2 H), 0.81 (t, J = 7.1 Hz, 3 H). LC-MS: m / z [M+H] + = 373.

[0816] Example 130

[0817] [ka]

[0818] 3-amino-7-chloro-8-(2-fluoro-6-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 8-Bromo-7-chloro-3-nitroimidazo[1,2-a]pyridine-2-carboxylate ethyl The procedure was the same as that for the synthesis of intermediate iv (routine 1, steps 1 and 2), and the title product (842 mg, 50%) was obtained using 4-chloro-3-bromopyridine-2-amine (1 g, 4.85 mmol) as the starting material. LCMS: m / z [M+H] + = 348.

[0819] Step 2: 8-Bromo-7-chloro-3-nitro-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as that for the synthesis of intermediate vi (route 1), and the title compound (350 mg, 0.97 mmol) was obtained using ethyl 8-bromo-7-chloro-3-nitroimidazo[1,2-a]pyridine-2-carboxylate (842 mg, 2.43 mmol) as the starting material. LC-MS: m / z [M+H] + = 361.

[0820] Step 3: 7-Chloro-8-(2-fluoro-6-methoxyphenyl)-3-nitro-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as the synthesis method in Example 110, and the target product (70 mg, 18%) was obtained using 8-bromo-7-chloro-3-nitro-N-propylimidazo[1,2-a]pyridine-2-carboxamide (350 mg, 0.97 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (200 mg, 1.18 mmol) as raw materials. LC-MS: m / z [M+H] + = 407.

[0821] Step 4: 7-Chloro-8-(2-fluoro-6-methoxyphenyl)-3-nitro-N-propylimidazo[1,2-a]pyridine-2-carboxamide (70 mg, 0.17 mmol) was added to methanol (5 mL) solution, iron powder (47.8 mg, 0.85 mmol) and ammonium chloride (91 mg, 1.70 mmol) were added, and the mixture was stirred at 80°C for 2 hours. The mixture was filtered and concentrated. The solution was purified on a preparative thin-layer plate (petroleum ether:ethyl acetate = 2:1) to obtain the target product (10 mg, yield: 15%), which was a yellow solid.

[0822] 1 H NMR (400 MHz, CD3OD) 8.10 (d, J = 7.4 Hz, 1H), 7.52 (d, J = 7.4 Hz, 1H), 7.01 (d, J = 7.7 Hz, 2H), 6.92 - 6.85 (m, 1H), 3.78 (s, 3H), 3.27 (d, J = 6.9 Hz, 2H), 1.58 (dd, J = 14.5, 7.1 Hz, 2H), 0.95 (t, J = 7.2 Hz, 3H). LCMS: m / z [M+H] + = 377.

[0823] Example 131

[0824] [ka]

[0825] 3-amino-N-(3,3-difluoroallyl)-7-fluoro-8-(2-fluoro-6-methoxyphenyl)imidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-7-fluoro-8-bromo-N-(3,3-difluoroallyl)imidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as that for the synthesis of intermediate vi (routine 1, step 2), and the target product was obtained using 3-amino-7-fluoro-8-bromoimidazo[1,2-a]pyridine-2-carboxylic acid and 3,3-difluoroprop-2-ene-1-amine as starting materials.

[0826] Step 2: The procedure was the same as the synthesis method in Example 110, using 3-amino-7-fluoro-8-bromo-N-(3,3-difluoroallyl)imidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.29 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) as raw materials to obtain the target product (58 mg, 51%), which was a yellow solid.

[0827] 1 HNMR (400MHz, DMSO-d6) 8.28 (t, J = 6.6 Hz, 1 H), 7.85 (t, J = 5.4 Hz, 1 H), 7.56 - 7.43 (m, 1 H), 7.10 - 6.88 (m, 3 H), 6.25 (br. s., 2 H), 4.73 - 4.47 (m, 1 H), 3.81 (br. s., 2 H), 3.74 (s, 3 H). LC-MS: m / z [M+H] + = 395.

[0828] Example 132

[0829] [ka]

[0830] 3-amino-8-(2-fluoro-6-methoxyphenyl)-7-methyl-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-7-methyl-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as that used for the synthesis of compounds iv (route 2) and vi (route 2). Using a 3-bromo-4-methylpyridine-2-amine solution (1.0 g, 5.35 mmol) as the starting material, the target product (86 mg, yield 5.2%) was obtained. LCMS: m / z [M+H] + =311.

[0831] Step 2: 3-amino-8-bromo-7-methyl-N-propylimidazo[1,2-a]pyridine-2-carboxamide (53 mg, 0.17 mmol) was dissolved in a mixture of dioxane and water (4 mL / 0.5 mL). Cesium carbonate (166 mg, 0.51 mmol), (2-fluoro-6-methoxyphenyl)boronic acid (87 mg, 0.51 mmol), tris(dibenzylideneacetone)dipalladium (Pd2(dba)3, CAS No.: 52409-22-0, 16 mg, 0.02 mmol), and 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (X-Phos, CAS No.: 564483-18-7, 16 mg, 0.03 mmol) were added sequentially, the mixture was protected with argon gas, and stirred at 100°C for 2 hours. 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, concentrated, and purified by column chromatography (petroleum ether:ethyl acetate = 1:0 to 0:1) to obtain the target product (12 mg, yield: 19%), which was a yellow solid.

[0832] 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 6.8 Hz, 1H), 7.39 (d, J = 6.7 Hz, 1H), 7.15 (s, 1H), 6.85 (t, J = 8.7 Hz, 2H), 6.73 (d, J = 6.8 Hz, 1H), 4.86 (s, 2H), 3.76 (s, 3H), 3.33 (d, J = 6.4 Hz, 2H), 2.13 (s, 3H), 1.62 - 1.54 (m, 2H), 0.94 (t, J = 7.3 Hz, 3H). LCMS: m / z [M+H] + = 357.

[0833] Example 133

[0834] [ka]

[0835] 3-amino-8-(2-fluoro-6-methoxyphenyl)-5-methyl-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-5-methylimidazo[1,2-a]pyridine-2-carboxylate ethyl ester The procedure was the same as for intermediate iv (pathway 2), using 3-bromo-6-methylpyridine-2-amine (1.5 g, 8 mmol) as the starting material to obtain the target product (700 mg, 30%). LC-MS: m / z [M+H] + = 298.

[0836] Step 2: 3,3-amino-8-bromo-5-methyl-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for intermediate iv (pathway 1), using 3-amino-8-bromo-5-methylimidazo[1,2-a]pyridine-2-carboxylate ethyl (300 mg, 1.0 mmol) as the starting material to obtain the target product (120 mg, 39%). LC-MS: m / z [M+H] + =311.

[0837] Step 3: The procedure was the same as in the synthesis example of compound vii, using 3-amino-8-bromo-5-methyl-N-propylimidazo[1,2-a]pyridine-2-carboxamide (30 mg, 0.1 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (25 mg, 0.15 mmol) as raw materials to obtain the title compound (10 mg, 28%).

[0838] 1 H NMR (400 MHz, DMSO-d6) 7.54 (s, 1H), 7.41 (d, J = 7.1 Hz, 1H), 6.97 (d, J = 8.4 Hz, 1H), 6.89 (t, J = 8.6 Hz, 1H), 6.78 (d, J = 6.8 Hz, 1H), 6.48 (d, J = 6.8 Hz, 1H), 5.87 (s, 2H), 3.69 (s, 3H), 3.21 - 3.08 (m, 2H), 2.94 (s, 3H), 1.46 (dd, J = 14.6, 7.3 Hz, 2H), 0.81 (t, J = 7.4 Hz, 3H). LC-MS: m / z [M+H] + =357.

[0839] Example 134

[0840] [ka]

[0841] 3-amino-8-(2-fluoro-6-methoxyphenyl)-6-methyl-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-amino-8-bromo-6-methylimidazo[1,2-a]pyridine-2-carboxylate ethyl ester The procedure was the same as for intermediate iv (pathway 2), using 3-bromo-5-methylpyridine-2-amine (500 mg, 2.7 mmol) as the starting material to obtain the target product (170 mg, 31%). LC-MS: m / z [M+H] + = 298.

[0842] Step 2: 3-amino-8-bromo-6-methyl-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as for intermediate vi (pathway 1), and compound (55 mg, 35%) was obtained using ethyl 3-amino-8-bromo-6-methylimidazo[1,2-a]pyridine-2-carboxylate (150 mg, 0.5 mmol) as the starting material. LC-MS: m / z [M+H] + =311.

[0843] Step 3: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-6-methyl-N-propylimidazo[1,2-a]pyridine-2-carboxamide (55 mg, 0.17 mmol) and 2-fluoro-6-methoxyphenylboronic acid (33 mg, 0.19 mmol) were used as raw materials to obtain the target product (17 mg, blue solid) in a yield of 28%.

[0844] 1 HNMR(400 MHz, DMSO-d6) 7.96 (s, 1H), 7.54 (t, J = 6.1 Hz, 1H), 7.43 (dd, J = 15.3, 8.3 Hz, 1H), 6.98 (d, J = 8.4 Hz, 1H), 6.91 (t, J = 8.6 Hz, 1H), 6.81 (d, J = 1.2 Hz, 1H), 6.03 (d, J = 9.6 Hz, 2H), 3.70 (s, 3H), 3.14 (dd, J = 14.1, 6.5 Hz, 2H), 2.28 (s, 3H), 1.46 (dd, J = 14.5, 7.3 Hz, 2H), 0.81 (t, J = 7.4 Hz, 3H) LC-MS: m / z [M+H] + =357.

[0845] Example 135

[0846] [ka]

[0847] Step 1: 3-amino-8-chloroimidazo[1,2-a]pyrazine-2-carboxylate ethyl 3-Chloropyrazine-2-amine (1 g, 7.7 mmol), ethyl glyoxylate (1.2 g, 11.6 mmol), and DBU (1.3 g, 11.6 mmol) were added to 8 mL of tetrahydrofuran, cooled to 0°C, and trimethylsilyl cyanide (1.15 g, 11.6 mmol) was added. The mixture was heated in a microwave at 120°C for 2 hours. After concentration, the title product (170 mg, green solid) was obtained by column chromatography (petroleum ether:ethyl acetate = 4:1) with a yield of 9.2%. LC-MS: m / z [M+H] + =241.

[0848] Step 2: 3-amino-8-(2-fluoro-6-methoxyphenyl)imidazo[1,2-a]pyrazine-2-carboxylate ethyl ester The procedure was the same as that for the synthesis of compound vii. Using ethyl 3-amino-8-chloroimidazo[1,2-a]pyrazine-2-carboxylate (200 mg, 0.83 mmol) and 2-fluoro-6-methoxyphenylboronic acid (156 mg, 0.92 mmol) as starting materials, the title product (113 mg, blue solid) was obtained, with a yield of 41%. LC-MS: m / z [M+H] + =331.

[0849] Step 3: 3-amino-8-(2-fluoro-6-methoxyphenyl)imidazo[1,2-a]pyrazine-2-carboxylic acid 3-amino-8-(2-fluoro-6-methoxyphenyl)imidazo[1,2-a]pyrazine-2-carboxylate ethyl (60 mg, 0.18 mmol) and lithium hydroxide monohydrate (62 mg, 1.5 mmol) were sequentially added to a mixture of 4 mL of tetrahydrofuran and 1 mL of water, and the mixture was left at room temperature for 2 hours. The pH was adjusted to 6 with trifluoroacetic acid to obtain the title product (50 mg, blue solid). LC-MS: m / z [M+H] + =303.

[0850] Step 4: 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-propylimidazo[1,2-a]pyrazine-2-carboxamide 3-amino-8-(2-fluoro-6-methoxyphenyl)imidazo[1,2-a]pyrazine-2-carboxylic acid (50 mg, 0.17 mmol) and HATU (97 mg, 0.25 mmol) were added to DMF (5 mL) and stirred at room temperature for 30 minutes. Then, triethylamine (50 mg, 0.5 mmol) and n-propylamine (12 mg, 0.20 mmol) were added, and stirring was continued at room temperature for 2 hours to obtain the target product (18 mg, yellow solid) with a yield of 33%.

[0851] 1 HNMR(400 MHz, DMSO-d6) 8.22 (d, J = 4.8 Hz, 1H), 7.90 (t, J = 6.0 Hz, 1H), 7.80 (d, J = 4.8 Hz, 1H), 7.50 (dd, J = 15.4, 8.3 Hz, 1H), 7.02 (d, J = 8.5 Hz, 1H), 6.94 (t, J = 8.7 Hz, 1H), 6.49 (s, 2H), 3.70 (s, 3H), 3.16 (dd, J = 13.8, 6.6 Hz, 2H), 1.47 (dd, J = 14.5, 7.3 Hz, 2H), 0.82 (t, J = 7.4 Hz, 3H) LC-MS: m / z [M+H] + = 344.

[0852] Example 136

[0853] [ka]

[0854] 3-amino-8-(2-fluoro-6-methoxyphenyl-3-deuterium)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: (2-Fluoro-6-methoxyphenyl-3-deuterium)boronic acid (2-fluoro-6-methoxyphenyl-3-bromo)boronic acid (200 mg, 0.8 mmol) was dissolved in deuterated methanol (CD3OD, 2 mL), and palladium carbon (30 mg, which had been pre-mixed in deuterated methanol for 24 hours) was added. The mixture was stirred at room temperature under a deuterium atmosphere for 2 hours. The mixture was filtered through diatomaceous earth to concentrate the organic phase, which was then used directly in the next step.

[0855] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (2-fluoro-6-methoxyphenyl-3-deuterium)boronic acid (115 mg, 0.68 mmol) were used as raw materials to obtain the target product (30 mg, 25%), which was a yellow solid.

[0856] 1 H NMR (400 MHz, DMSO-d6) 8.09 - 8.24 (m, 1 H) 7.52 - 7.68 (m, 1 H) 7.39 - 7.51 (m, 1 H) 6.97 - 7.03 (m, 1 H) 6.82 - 6.95 (m, 2 H) 6.14 (s, 2 LC-MS: m / z [M+1] + = 344.

[0857] Example 137

[0858] [ka]

[0859] 3-amino-8-(2-fluoro-6-methoxyphenyl-5-deuterium)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: (2-Fluoro-6-methoxy-5-deuterium)boric acid (2-fluoro-6-methoxyphenyl-5-bromo)boronic acid (200 mg, 0.8 mmol) was dissolved in deuterated methanol (CD3OD, 2 mL), and palladium carbon (30 mg, which had been pre-mixed in deuterated methanol for 24 hours) was added. The mixture was stirred at room temperature under a deuterium atmosphere for 2 hours. The mixture was filtered through diatomaceous earth to concentrate the organic phase, which was then used directly in the next step.

[0860] Step 2: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and (2-fluoro-6-methoxy-5-deuterium)boronic acid (120 mg, 0.68 mmol) were used as raw materials to obtain the target product (26 mg, 23%), which was a white solid.

[0861] 1 H NMR (400 MHz, DMSO-d6) 8.15 (d, J=6.85 Hz, 1 H) 7.58 (br. s., 1 H) 7.43 (s, 1 H) 6.84 - 6.96 (m, 3 H) 6.14 (s, 2 H) 3.70 (s, 3 H) 3.15 (d, J=6.85 Hz, 2 H) 1.46 (d, J=7.34 Hz, 2 H) 0.81 (t, J=7.34 Hz, 3 H).LC-MS: m / z [M+1] + = 344.

[0862] Example 138

[0863] [ka]

[0864] 3-amino-8-(2-fluoro-6-(methoxy-d3)phenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 2-Bromo-1-fluoro-3-(methoxy-d3)benzene 2-Bromo-3-fluorophenol (1 g, 5.26 mmol) was dissolved in acetonitrile (30 mL), potassium carbonate (1.45 g, 10.5 mmol) and deuterated methyl iodide (CAS No.: 865-50-9, 2.28 g, 15.75 mmol) were added, the mixture was stirred at 50°C for 5 hours, filtered, concentrated, water (50 mL) was added, and the mixture was extracted with dichloromethane (50 mL x 3). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated to obtain 0.93 g of crude product.

[0865] Step 2: 2-(2-fluoro-6-(methoxy-d3)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 2-Bromo-1-fluoro-3-(methoxy-d3)benzene (800 mg, 3.85 mmol), bis(pinacolate)diborone (1.47 g, 5.78 mmol), potassium acetate (754 mg, 7.7 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane adduct (314 mg, 0.39 mmol) were sequentially added to dioxane, protected with argon gas, and stirred at 100°C for 16 hours. The mixture was concentrated and purified by column chromatography (petroleum ether:ethyl acetate = 10:1) to obtain the target product (610 mg, 62%), which was a white solid.

[0866] Step 3: Using the same procedure as in the synthesis example of compound vii, 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol) and 2-(2-fluoro-6-(methoxy-d3)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (173 mg, 0.68 mmol) were used as raw materials to obtain the target product (70 mg, 60%), which was a yellow solid.

[0867] 1H NMR (400MHz, DMSO-d6) 8.16 (d, J = 6.4 Hz, 1 H), 7.57 (br. s., 1 H), 7.49 - 7.38 (m, 1 H), 7.03 - 6.85 (m, 4 H), 6.15 (br. s., 2 H), 3.16 (d, J = 6.8 Hz, 2 H), 1.52 - 1.43 (m, 2 H), 0.82 (t, J = 7.1 Hz, 3 H). LC-MS: m / z [M+H] + = 346.

[0868] Example 139 3-amino-8-(1,3-dimethyl-1H-pyrazole-4-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide

[0869] [ka]

[0870] The procedure was the same as that for the synthesis of compound vii. Using 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (0.1 g, 0.34 mmol) and 1,3-dimethyl-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.11 g, 0.51 mmol) as raw materials, the target product (25 mg, 24%) was obtained, which was a yellow solid.

[0871] 1 HNMR (400MHz, DMSO-d6) 8.86 (s, 1 H), 8.01 (d, J = 5.4 Hz, 2 H), 7.19 (d, J = 4.9 Hz, 1 H), 6.92 - 6.76 (m, 1 H), 6.10 (br. s., 2 H), 3.87 (s, 3 H), 3.27 (d, J = 5.4 Hz, 2 H), 2.41 (s, 3 H), 1.57 (d, J = 6.4 Hz, 2 H), 0.97 - 0.84 (m, 3 H).LC-MS: m / z [M+1] += 313.

[0872] Example 140 3-amino-8-(1-methyl-1H-imidazole-5-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide

[0873] [ka]

[0874] The procedure was the same as that for the synthesis of compound vii. Using 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (0.1 g, 0.64 mmol) and 1-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole (0.11 g, 0.51 mmol) as raw materials, the target product (20 mg, 19%) was obtained, which was a yellow solid.

[0875] 1 HNMR (400MHz, DMSO-d6) 8.17 (d, J = 6.8 Hz, 1 H), 7.89 (s, 1 H), 7.84 (s, 1 H), 7.14 (d, J = 6.8 Hz, 1 H), 6.91 (t, J = 8 Hz, 1 H), 6.19 (s, 2 LC-MS: m / z [M+1] + = 299.

[0876] Example 141 3-amino-8-(5-methyl-1,2-oxazol-4-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide

[0877] [ka]

[0878] The procedure was the same as that for the synthesis of compound vii. Using 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (0.1 g, 0.34 mmol) and 5-methyl-4-(tetramethyl-1,3,2-diboran-2-yl)-1,2-oxazole (0.11 g, 0.51 mmol) as raw materials, the target product (35 mg, 34%) was obtained, which was a yellow solid.

[0879] 1 H NMR (400MHz, DMSO-d6) 9.49 (s, 1 H), 8.15 (d, J = 6.8 Hz, 1 H), 8.07 (t, J = 5.6 Hz, 1 H), 7.23 (d, J = 6.8 Hz, 1 H), 6.92 (t, J = 6.8 Hz, 1 H), 6.18 (s, 2 H), 3.24 (q, J = 6.7 Hz, 2 H), 2.67 (s, 3 H), 1.61 - 1.47 (m, 2 H), 0.89 (t, J = 7.3 Hz, 3 H). LC-MS: m / z [M+1] + = 300.

[0880] Example 142 3-amino-8-(2-methylpyridine-3-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide

[0881] [ka]

[0882] The procedure was the same as that for the synthesis of compound vii. Using 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (0.1 g, 0.34 mmol) and (2-methylpyridine-3-yl)boronic acid (0.07 g, 0.51 mmol) as raw materials, the target product (40 mg, 38%) was obtained, which was a yellow solid.

[0883] 1H NMR (400MHz, DMSO-d6) 8.52 (d, J = 4.9 Hz, 1 H), 8.21 (d, J = 6.8 Hz, 1 H), 7.72 (d, J = 7.3 Hz, 1 H), 7.68 - 7.61 (m, 1 H), 7.33 (dd, J = 4.9, 7.3 Hz, 1 H), 7.00 (d, J = 6.8 Hz, 1 H), 6.95 - 6.88 (m, 1 H), 6.21 (s, 2 H), 3.21 - 3.09 (m, 2 H), 2.35 (s, 3 H), 1.51 - 1.40 (m, 2 H), 0.85 - 0.75 (m, 3 H). LC-MS: m / z [M+1] + = 310.

[0884] Example 143

[0885] [ka]

[0886] 3-amino-8-isobutyl-N-propylimidazo[1,2-a]pyridine-2-carboxamide hydrochloride 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (100 mg, 0.34 mmol), (2-methylpropyl)boronic acid (173 mg, 1.7 mmol), cesium carbonate (221 mg, 0.68 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct (CAS number: 95464-05-4, 25 mg, 0.03 mmol) were sequentially added to a toluene-water mixture (2 mL / 0.2 mL), protected with argon gas, and stirred at 100°C for 2 hours. 20 mL of water was added, and the mixture was extracted with dichloromethane (20 mL x 3). The organic phase was concentrated, and the product was obtained by column chromatography (petroleum ether:ethyl acetate = 1:1 to 1:5). This product was dissolved in dichloromethane (10 mL), hydrochloric acid (4 M methanol solution, 2 mL) was added, the mixture was stirred for 5 minutes, and the solution was concentrated to obtain the target product (70 mg, 66%), which was an off-white solid.

[0887] 1 H NMR (400MHz, DMSO-d6) 8.49 (br. s., 1 H), 7.55 (br. s., 1 H), 7.31 (br. s., 1 H), 3.29 (br. s., 2 H), 2.91-2.87 (m, 2 H), 2.09-2.05 (m, 1 H), 1.58 (d, J = 6.4 Hz, 2 H), 0.95-0.91 (m, 9 H). LC-MS: m / z [M+H] + = 275.

[0888] Example 144

[0889] [ka]

[0890] 3-amino-8-(5-fluoro-2-methoxyphenoxy)-N-propylimidazo[1,2-a]pyridine-2-carboxamide Step 1: 3-(5-fluoro-2-methoxyphenoxy)-2-nitropyridine 3-Fluoro-2-nitropyridine (1 g, 7.04 mmol), 5-fluoro-2-methoxyphenol (800 mg, 7.04 mmol), and cesium carbonate (4.6 g, 14.08 mmol) were dissolved in 20 mL of acetonitrile and stirred at room temperature for 2 hours. 20 mL of water was added, and the mixture was extracted with dichloromethane (30 mL x 2). The organic phase was dried and concentrated, and purified by column chromatography (dichloromethane) to obtain 1.6 g of a pale yellow solid. LC-MS: m / z [M+1] + = 265.

[0891] Step 2: 3-(5-fluoro-2-methoxyphenoxy)pyridine-2-amine Under a hydrogen gas atmosphere, 3-(5-fluoro-2-methoxyphenoxy)-2-nitropyridine (1.6 g, 6.06 mmol) and Raney nickel (100 mg) were dissolved in 20 mL of methanol, stirred at room temperature for 2 hours, the solid was filtered, and the organic phase was concentrated to obtain 1.2 g of crude product, which was used directly in the next step. LC-MS: m / z [M+1] + = 235.

[0892] Step 3: 8-(5-fluoro-2-methoxyphenoxy)imidazo[1,2-a]pyridine-2-carboxylate ethyl ester 3-(5-fluoro-2-methoxyphenoxy)pyridine-2-amine (1.2 g, 5.12 mmol) and ethyl bromopyruvate (1.2 g, 6.14 mmol) were dissolved in ethanol (20 mL), heated to 90°C, and stirred for 16 hours. The organic phase was concentrated and purified by column chromatography (petroleum ether:ethyl acetate = 10:1) to obtain 2 g of a yellow oily substance. LC-MS: m / z [M+1] + = 331.

[0893] Step 4: 8-(5-fluoro-2-methoxyphenoxy)-3-nitroimidazo[1,2-a]pyridine-2-carboxylate ethyl 8-(5-fluoro-2-methoxyphenoxy)imidazo[1,2-a]pyridine-2-carboxylate ethyl (2 g, 6.05 mmol), trifluoroacetic acid (0.8 g, 7.26 mmol), and trifluoroacetic anhydride (1.5 g, 7.26 mmol) were dissolved in 1,2-dichloroethane (20 mL), cooled to 0°C, and tetrabutylammonium nitrate (CAS No.: 1941-27-1, 1.8 g, 6.05 mmol) was added in batches. The mixture was stirred for 1 hour while maintaining 0°C, 20 mL of water was added, and the pH was neutralized to 7 with aqueous sodium bicarbonate solution. The mixture was extracted with dichloromethane (50 mL x 2), the organic phase was dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (petroleum ether:ethyl acetate = 1:1) to obtain 300 mg of yellow solid. LC-MS: m / z [M+1] + = 376.

[0894] Step 5: 3-amino-8-(5-fluoro-2-methoxyphenoxy)imidazo[1,2-a]pyridine-2-carboxylate ethyl 300 mg, 0.8 mmol of 8-(5-fluoro-2-methoxyphenoxy)-3-nitroimidazo[1,2-a]pyridine-2-carboxylate ethy (260 mg, 4 mmol) and zinc powder (260 mg, 4 mmol) were dissolved in 10 mL of methanol. 2 mL of saturated ammonium chloride aqueous solution was added, and the mixture was stirred at room temperature for 2 hours. The solid was filtered, 30 mL of water was added, and the mixture was extracted with dichloromethane (50 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated to obtain 200 mg of crude product, which was used directly in the next step. LC-MS: m / z [M+1] + = 346.

[0895] Step 6: Dissolve 3-amino-8-(5-fluoro-2-methoxyphenoxy)imidazo[1,2-a]pyridine-2-carboxylate ethyl (200 mg, 0.58 mmol) in 5 mL of n-propylamine, heat in a sealed container to 120°C and stir overnight, concentrate the reaction solution, and purify it on a preparative plate (petroleum ether:ethyl acetate = 1:1) to obtain the target product (32 mg, 15%), which was a gray solid.

[0896] 1 H NMR (400 MHz, DMSO-d6) δ 7.97 (t, J = 6.0 Hz, 1H), 7.88 (d, J = 6.6 Hz, 1H), 7.22 (dd, J = 9.7, 5.3 Hz, 1H), 7.14 - 7.07 (m, 2H), 6.67 (t, J = 7.2 Hz, 1H), 6.18 (s, 2H), 6.12 (d, J = 7.3 Hz, 1H), 3.74 (s, 3H), 3.22 (dd, J = 13.7, 6.5 Hz, 2H), 1.59 - 1.47 (m, 2H), 0.87 (t, J = 7.4 Hz, 3H). LC-MS: m / z [M+1] + = 359.

[0897] Example 145 3-amino-8-(6-fluoropyridine-2-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide

[0898] [ka]

[0899] The procedure was the same as that for the synthesis of compound vii. Using 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (0.1 g, 0.34 mmol) and (6-fluoropyridine-2-yl)boronic acid (0.72 g, 0.51 mmol) as raw materials, the target product (67 mg, 63%) was obtained, which was a yellow solid.

[0900] 1 H NMR (400MHz, DMSO-d6) 9.40 (d, J = 7.3 Hz, 1 H), 8.29 (d, J = 6.8 Hz, 1 H), 8.12 (td, J = 8.1, 16.5 Hz, 3 H), 7.24 - 7.16 (m, 1 H), 7.08 - 6.97 (m, 1 H), 6.23 (s, 2 H), 3.31 - 3.19 (m, 2 H), 1.65 - 1.49 (m, 2 H), 0.98 - 0.85 (m, 3 H). LC-MS: m / z [M+1] + = 314.

[0901] Example 146

[0902] [ka]

[0903] 3-amino-8-(cyclohexa-1-en-1-yl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure was the same as that for the synthesis of compound vii. Using 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (0.1 g, 0.34 mmol) and 2-(cyclohexa-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (218 mg, 1.05 mmol) as raw materials, the target product (50 mg, 51%) was obtained, which was a yellow solid.

[0904] 1 H NMR (400MHz ,DMSO-d6) 7.99 (d, J = 6.8 Hz, 1 H), 7.80 (t, J = 6.1 Hz, 1 H), 7.30 (d, J = 5.9 Hz, 1 H), 6.99 (d, J = 6.8 Hz, 1 H), 6.79 (t, J = 6.8 Hz,1 H), 6.06 (s, 2 H), 3.28 - 3.19 (m, 2 H), 2.56 - 2.51 (m, 2 H), 2.28 (br. s., 2 H), 1.79 - 1.71 (m, 2 H), 1.65 (d, J = 5.4 Hz, 2 H), 1.59 - 1.48 (m, 2 H), 0.93 - 0.84 (m, 3 H) LC-MS: m / z [M+1] + = 285.

[0905] Example 147 3-amino-8-cyano-N-propylimidazo[1,2-a]pyridine-2-carboxamide

[0906] [ka]

[0907] 3-amino-8-bromo-N-propylimidazo[1,2-a]pyridine-2-carboxamide (0.1 g, 0.34 mmol), zinc cyanide (0.020 g, 0.17 mmol), zinc powder (0.0022 g, 0.034 mmol), tris(dibenzyldiacetone)dipalladium(0) (0.016 g, 0.017 mmol), and X-PHOS (CAS No.: 564483-18-7, 0.016 g, 0.034 mmol) were sequentially added to N,N-dimethylacetamide (4 mL), protected with argon gas, and stirred at 140 °C for 3 hours. After adding 40 ml of water, the mixture was extracted with ethyl acetate (40 ml x 2), concentrated, and the target product (61 mg, 52%) was obtained by column chromatography, which was a yellow solid.

[0908] 1 HNMR (400MHz, DMSO-d6) 8.48-8.46 (m, 1 H), 8.02-7.97 (m, 1 H), 7.83-7.77 (m, 1 H), 7.02-6.95 (m, 1 H), 6.38 (s, 2 H), 3.28 - 3.20 (m, 2 H), 1.58-1.50 (m, 2 H), 0.92-0.84 (m, 3 H). LC-MS: m / z [M+1] + = 244.

[0909] Example 148 3-amino-7-cyano-8-(2-fluoro-6-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide

[0910] [ka]

[0911] Step 1: 8-chloro-7-iodo-3-nitroimidazo[1,2-a]pyridine-2-carboxylate ethyl ester The procedure was the same as that for the synthesis of intermediate iv (routine 1, step 1, step 2). Using 3-chloro-4-iodopyridine-2-amine (10 g, 39.3 mmol) as the starting material, the title product (7.75 g, yield: 50%) was obtained, which was a yellow solid. LCMS: m / z [M+H] + =396.

[0912] Step 2: 8-Chloro-7-iodo-3-nitroimidazo[1,2-a]pyridine-2-carboxylic acid Ethyl 8-chloro-7-iodo-3-nitroimidazo[1,2-a]pyridine-2-carboxylate (1 g, 2.5 mmol) was added to a mixed solution of tetrahydrofuran (10 mL) and water (10 mL), and lithium hydroxide (181 mg, 7.6 mmol) was added. The mixture was stirred at 25°C for 2 hours. The reaction mixture was added to water (100 mL) and extracted with ethyl acetate (100 mL). The aqueous phase was adjusted to pH < 7 with 1 M hydrochloric acid. Extraction with ethyl acetate (100 mL x 2) was performed, the organic phase was combined, and the mixture was concentrated to obtain the title compound (804 mg, yield: 86.5%), which was a yellow solid. LCMS: m / z [M+H] + = 368.

[0913] Step 3: 8-Chloro-7-iodo-3-nitro-N-propylimidazo[1,2-a]pyridine-2-carboxamide 8-Chloro-7-iodo-3-nitroimidazo[1,2-a]pyridine-2-carboxylic acid (800 mg, 2.2 mmol) was added to dichloromethane (20 mL), followed by the sequential addition of triethylamine (661 mg, 6.5 mmol) and propylphosphonic anhydride (2.7 g, 4.4 mmol). The mixture was stirred at 25°C for 0.5 hours. Next, n-propylamine (193 mg, 3.3 mmol) was added to the mixture and the mixture was stirred at 25°C for 2 hours. A saturated aqueous solution of ammonium chloride (100 mL) was added, and the mixture was extracted with dichloromethane (100 mL x 2). The organic layer was washed with brine and dried over anhydrous sodium sulfate. Purification by column chromatography (petroleum ether:ethyl acetate = 10:1~2:1) yielded the title compound (580 mg, yield: 65.2%), which was a yellow solid. LCMS: m / z [M+H] += 409.

[0914] Step 4: 8-Chloro-7-cyano-3-nitro-N-propylimidazo[1,2-a]pyridine-2-carboxamide 8-Chloro-7-iodo-3-nitro-N-propylimidazole[1,2-a]pyridine-2-carboxamide (560 mg, 1.4 mmol) was added to a solution of N,N-dimethylformamide (5 mL), and cuprous cyanide (368 mg, 4.1 mmol) was added. The mixture was stirred at 120°C for 1 hour using a microwave. The mixture was added dropwise to 20 mL of water and filtered. The cake was concentrated to obtain the title compound (445 mg, crude product), which was a yellow solid. LCMS: m / z [M+H] + = 308.

[0915] Step 5: 3-amino-8-chloro-7-cyano-N-propylimidazo[1,2-a]pyridine-2-carboxamide 8-Chloro-7-cyano-3-nitro-N-propylimidazo[1,2-a]pyridine-2-carboxamide (200 mg, 0.65 mmol) was added to ethanol (3 mL), zinc powder (0.43 g, 6.5 mmol), and ammonium chloride (347 mg, 6.5 mmol), and the mixture was stirred at 25°C for 2 hours. The mixture was filtered. The filtrate was concentrated to obtain the title compound (120 mg, crude product), which was a yellow solid. LCMS: m / z [M+H] + = 278.

[0916] Step 6: 3-amino-8-chloro-7-cyano-N-propylimidazo[1,2-a]pyridine-2-carboxamide (60 mg, 0.22 mmol) was added to a mixture of 1,4-dioxane (1.5 mL) and water (0.5 mL). Cesium carbonate (215 mg, 0.66 mmol), (2-fluoro-6-methoxy)phenylboronic acid (112 mg, 0.66 mmol), tris(dibenzylideneacetone)dipalladium (20 mg, 0.022 mmol), and X-PHOS (11 mg, 0.022 mmol) were added, and the mixture was protected with argon gas and stirred at 100°C for 2 hours. Water (100 mL) was added to the mixture and extracted with ethyl acetate (100 mL). The organic layer was rinsed with brine and dried over anhydrous sodium sulfate. The target product (24 mg, yield: 30%) was obtained by purification using column chromatography (petroleum ether:ethyl acetate = 10:1 to 2:1), and was a yellow solid.

[0917] 1 H NMR (400 MHz, DMSO-d6) δ 8.33 (d, J = 5.7 Hz, 1H), 7.85-7.81 (m, 1H), 7.59 - 7.50 (m, 1H), 7.20 (d, J = 5.9Hz, 1H), 7.09 (d, J = 6.9 Hz, 1H), 7.01 (t, J = 8.5 Hz, 1H), 6.59 (s, 2H), 3.76 (s, 3H), 3.18-3.13 (m, 2H), 1.47 (dd, J = 14.0, 7.0 Hz, 2H), 0.81 (t, J = 6.6 Hz, 3H).LCMS: m / z [M+H] + = 368.

[0918] Example 149 3-amino-8-(3-methylmorpholino)-N-propylimidazo[1,2-a]pyridine-2-carboxamide

[0919] [ka]

[0920] Step 1: 8-Fluoro-3-nitroimidazo[1,2-a]pyridine-2-carboxylate ethyl The procedure was the same as that for the synthesis of intermediate iv (routine 1, steps 1 and 2). Using 3-fluoropyridine-2-amine (1.5 g, 13.4 mmol) and ethyl bromopyruvate (3.9 g, 20 mmol) as raw materials, the target product (500 mg, yield: 15%) was obtained as a yellow solid. LC-MS: m / z [M+1] + = 254.

[0921] Step 2: 8-(3-methylmorpholino)-3-nitroimidazo[1,2-a]pyridine-2-carboxylate ethyl Ethyl 8-fluoro-3-nitroimidazo[1,2-a]pyridine-2-carboxylate (200 mg, 0.79 mmol) and 3-methylmorpholine (160 mg, 1.58 mmol) were dissolved in dimethyl sulfoxide (5 mL), heated to 100 °C, and stirred for 12 hours. The reaction solution was cooled, diluted with 50 mL of water, extracted with ethyl acetate (20 mL x 3), the organic phase was dried over anhydrous sodium sulfate, concentrated, and the target product (200 mg, yield: 76%) was obtained by column chromatography (petroleum ether:ethyl acetate = 5:1), which was a white solid.

[0922] Step 3: 8-(3-methylmorpholino)-3-nitro-N-propylimidazo[1,2-a]pyridine-2-carboxamide 8-(3-methylmorpholinyl)-3-nitroimidazo[1,2-a]pyridine-2-carboxylate ethyl (200 mg, 0.60 mmol) was dissolved in n-propylamine (5 mL), heated to 100°C in a sealed container, and stirred for 12 hours. The reaction solution was concentrated to obtain the target product (200 mg, crude product), which was a white solid.

[0923] Step 4: 8-(3-methylmorpholino)-3-nitro-N-propylimidazo[1,2-a]pyridine-2-carboxamide (150 mg, 0.58 mmol), zinc powder (379 mg, 5.8 mmol), and saturated ammonium chloride aqueous solution (1 mL) were dissolved in methanol (5 mL) and stirred at room temperature for 1 hour. Water (20 mL) was added, and the mixture was extracted with dichloromethane (20 mL x 3). The organic phase was dried over anhydrous sodium sulfate, concentrated, and purified on a preparative plate (ethyl acetate) to obtain the target product (20 mg, yield: 11%), which was a white solid.

[0924] 1 H NMR (400 MHz, DMSO-d6) 7.72 - 7.80 (m, 1 H) 7.64 - 7.70 (m, 1 H) 6.66 - 6.72 (m, 1 H) 6.21 - 6.26 (m, 1 H) 5.99 (s, 2 H) 5.10 - 5.19 (m, 1 H) 3.83 - 3.96 (m, 2 H) 3.59 - 3.69 (m, 2 H) 3.15 - 3.26 (m, 4 H) 1.48 - 1.58 (m, 2 H) 0.94 (d, J=6.85 Hz, 3 H) 0.85 - 0.90 (m, 3 H). LC-MS: m / z [M+1] + = 318.

[0925] Example 150 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-7-deuterium-2-carboxamide

[0926] [ka]

[0927] Step 1: 3-Chloropyridine-4-Deuterium-2-amine 3-Chloro-4-iodopyridine-2-amine (2 g, 8 mmol) was dissolved in deuterated methanol (10 mL), and Raney nickel (200 mg, pre-dissolved in deuterated methanol, stirred for 10 minutes, filtered, and this procedure was repeated three times) was added. The mixture was stirred at 50°C for 72 hours under a deuterium atmosphere, filtered, and the filtrate was concentrated and purified by column chromatography to obtain an off-white solid (500 mg, yield: 48%). LC-MS: m / z [M+1] + = 130.

[0928] Step 2: 3-amino-8-chloro-N-propylimidazo[1,2-a]pyridine-7-deuterium-2-carboxamide The procedure was the same as for intermediates iv (pathway 1) and vi (pathway 2). Using 3-chloropyridine-4-deuterium-2-amine (500 mg, 3.85 mmol) as the starting material, the target product (200 mg, 20%) was obtained as a yellowish-green solid. LC-MS: m / z [M+1] + = 254.

[0929] Step 3: The procedure was the same as the synthesis method in Example 110, using 3-amino-8-chloro-N-propylimidazo[1,2-a]pyridine-7-deuterium-2-carboxamide (100 mg, 0.32 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) as raw materials to obtain the target product (70 mg, 64%), which was a yellow solid.

[0930] 1 H NMR (400MHz, DMSO-d6) 8.15 (d, J = 6.8 Hz, 1 H), 7.57 (br. s., 1 H), 7.45-7.40 (m, 1 H), 6.98 (d, J = 8.3 Hz, 1 H), 6.94 - 6.85 (m, 2 H), 6.13(br. s., 2 H), 3.70 (s, 3 H), 3.17-3.13 (m, 2 H), 1.55 - 1.37 (m, 2 H), 0.81 (t, J = 7.3 Hz, 3 H). LC-MS: m / z [M+1] += 344.

[0931] Example 151 3-amino-8-((2-fluoro-6-methoxybenzyl)oxy)-N-propylimidazo[1,2-a]pyridine-2-carboxamide

[0932] [ka]

[0933] Step 1: 8-((2-fluoro-6-methoxybenzyl)oxy)-3-nitroimidazo[1,2-a]pyridine-2-carboxylic acid Ethyl 8-fluoro-3-nitroimidazo[1,2-a]pyridine-2-carboxylate (200 mg, 0.79 mmol), (2-fluoro-6-methoxyphenyl)methanol (247 mg, 1.58 mmol), and cesium carbonate (772 mg, 2.37 mmol) were dissolved in N,N-dimethylformamide (5 mL) and heated to 100 °C and stirred for 2 hours. The reaction solution was cooled, diluted with 50 mL of water, neutralized with dilute hydrochloric acid, extracted with dichloromethane (20 mL x 3), and the organic phase was dried and concentrated over anhydrous sodium sulfate to obtain the target product (250 mg, crude product), which was a white solid.

[0934] Step 2: 8-((2-fluoro-6-methoxybenzyl)oxy)-3-nitro-N-propylimidazo[1,2-a]pyridine-2-carboxamide 8-((2-fluoro-6-methoxybenzyl)oxy)-3-nitroimidazo[1,2-a]pyridine-2-carboxylic acid (250 mg, 0.69 mmol) was dissolved in dichloromethane (10 mL), oxalyl chloride (1 mL) and one drop of N,N-dimethylformamide were added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated and dissolved in dichloromethane (10 mL), n-propylamine (0.5 mL) and triethylamine (0.5 mL) were added, and the mixture was stirred at room temperature for 2 hours. The reaction solution was washed with saturated ammonium chloride aqueous solution, the organic phase was dried and concentrated, and purified by column chromatography (petroleum ether:ethyl acetate = 1:1) to obtain the target product (200 mg, yield: 72%), which was a yellow solid.

[0935] Step 3: 8-((2-fluoro-6-methoxybenzyl)oxy)-3-nitro-N-propylimidazo[1,2-a]pyridine-2-carboxamide (200 mg, 0.5 mmol), zinc powder (327 mg, 5 mmol), and saturated ammonium chloride aqueous solution (1 mL) were dissolved in methanol (5 mL) and stirred at room temperature for 1 hour. Water (30 mL) was added, and the mixture was extracted with dichloromethane (30 mL x 3). The organic phase was dried over anhydrous sodium sulfate, concentrated, and purified on a preparative plate (petroleum ether:ethyl acetate = 1:1) to obtain the target product (54 mg, yield: 29%), which was a white solid.

[0936] 1 H NMR (400 MHz, DMSO-d6)7.91 (br. s., 1 H) 7.78 (d, J=6.85 Hz, 1 H) 7.41 - 7.52 (m, 1 H) 6.97 (d, J=8.31 ​​Hz, 1 H) 6.91 (s, 1 H) 6.65 - 6.78 LC-MS: m / z [M+1] + = 373.

[0937] Example 154 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-6-deuterium-2-carboxamide

[0938] [ka]

[0939] Step 1: 3-Chloropyridine-5-Deuterium-2-amine 3-Chloro-5-iodopyridine-2-amine (2 g, 8 mmol) was dissolved in deuterated methanol (10 mL), and Raney nickel (200 mg, pre-dissolved in deuterated methanol, stirred for 10 minutes, filtered, and this procedure was repeated three times) was added. The mixture was stirred at 50°C for 72 hours under a deuterium atmosphere, filtered, and the filtrate was concentrated and purified by column chromatography to obtain an off-white solid (400 mg, yield: 39%). LC-MS: m / z [M+1] + = 130.

[0940] Step 2: 3-amino-8-chloro-N-propylimidazo[1,2-a]pyridine-6-deuterium-2-carboxamide The procedure was the same as for intermediates iv (pathway 1) and vi (pathway 2). Using 3-chloropyridine-5-deuterium-2-amine (400 mg, 3.1 mmol) as the starting material, the target product (150 mg, 19%) was obtained as a yellowish-green solid. LC-MS: m / z [M+1] + = 254.

[0941] Step 3: The procedure was the same as the synthesis method in Example 110, using 3-amino-8-chloro-N-propylimidazo[1,2-a]pyridine-6-deuterium-2-carboxamide (100 mg, 0.32 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) as raw materials to obtain the target product (68 mg, 64%), which was a yellow solid.

[0942] 1H NMR (400MHz, DMSO-d6) 8.17 (br. s., 1 H), 7.60 (br. s., 1 H), 7.46-7.41 (m, 1 H), 7.00 (d, J = 8.3 Hz, 1 H), 6.97 - 6.88 (m, 2 H), 6.15 (br. s., 2H), 3.71 (s, 3 H), 3.24 - 3.11 (m, 2 H), 1.50-1.46 (m, 2 H), 0.88 - 0.77 (m, 3 H).LC-MS: m / z [M+1] + = 344.

[0943] Example 155

[0944] [ka]

[0945] 3-amino-6-fluoro-8-(2-fluoro-6-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-2-carboxamide The procedure for intermediate iv (pathway 1), intermediate vi (pathway 2), and compound vii was the same. Using 3-bromo-5-fluoropyridine-2-amine (1 g, 5.26 mmol) as the starting material, the target product (100 mg, yield: 5%) was obtained, which was a yellow solid.

[0946] 1 H NMR (400MHz, DMSO-d6) = 8.38 (br. s., 1 H), 7.65 (br. s., 1 H), 7.48 (d, J = 7.8 Hz, 1 H), 7.12 (d, J = 8.3 Hz, 1 H), 7.03 (d, J = 8.3 Hz, 1 H), 6.95 (t, J= 8.3 Hz, 1 H), 6.20 (br. s., 1 H), 3.74 (s, 3 H), 3.23 - 3.11 (m, 2 H), 1.49-1.45 (m, 2 H), 0.83 (br. s., 3 H). LC-MS: m / z [M+1] + = 361.

[0947] Example 156

[0948] [ka]

[0949] Step 1: 3-Chloropyridine-6-deuterium-2-amine 3-Chloro-6-bromopyridine-2-amine (1 g, 4.85 mmol) was dissolved in deuterated methanol (10 mL), and Raney nickel (200 mg, previously dissolved in deuterated methanol, stirred for 10 minutes, filtered, and this procedure was repeated three times) was added. The mixture was stirred at 50°C under a deuterium atmosphere for 72 hours, filtered, and the filtrate was concentrated. An off-white solid (200 mg, yield: 32%) was obtained by column chromatography. LC-MS: m / z [M+1] + = 130.

[0950] Step 2: 3-amino-8-chloro-N-propylimidazo[1,2-a]pyridine-5-deuterium-2-carboxamide The procedure was the same as for intermediates iv (pathway 1) and vi (pathway 2). Using 3-chloropyridine-5-deuterium-2-amine (200 mg, 1.55 mmol) as the starting material, the target product (100 mg, 25%) was obtained as a yellowish-green solid. LC-MS: m / z [M+1] + = 254.

[0951] Step 3: 3-amino-8-(2-fluoro-6-methoxyphenyl)-N-propylimidazo[1,2-a]pyridine-5-deuterium-2-carboxamide The procedure was the same as the synthesis method in Example 110, using 3-amino-8-chloro-N-propylimidazo[1,2-a]pyridine-5-deuterium-2-carboxamide (100 mg, 0.32 mmol) and (2-fluoro-6-methoxyphenyl)boronic acid (115 mg, 0.68 mmol) as raw materials to obtain the target product (60 mg, 54%), which was a yellow solid.

[0952] 1 H NMR (400MHz, DMSO-d6) 7.58 (br. s., 1 H), 7.46-7.40 (m, 1 H), 6.98 (d, J = 8.3 Hz, 1 H), 6.95 - 6.84 (m, 3 H), 6.14(br. s., 2 H), 3.70 (s, 3 H), 3.18-3.12 (m, 2 H), 1.53 - 1.39 (m, 2 H), 0.81 (t, J = 7.3 Hz, 3 H). LC-MS: m / z [M+1] + = 344.

[0953] Bioactivity data Cell line construction and subculturing The α subunit, β subunit, and γ subunit form a complete, functional GABA. A It is essential for receptor formation. In this example, the present invention constructs a lipofection method (Felgner, PL, et al. Proceedings of the National Academy of Sciences, 1987, 84: 7413-7417) and α2-GABA A Receptor (α2-GABA A HEK293 cells that stably express α2-GABA were screened. A In the R-HEK293 cell model, the α2 subunit (protein sequence, see GenBank registry number: NM_000807.4), β3 subunit (protein sequence, see GenBank registry number: NM_000814.5), and γ2 subunit (protein sequence, see GenBank registry number: NM_000816.3) were simultaneously expressed.

[0954] The above cell lines were subcultured. The proliferated α2-GABA A Using R-HEK293 cells, GABA A The affinity of compounds to the benzodiazepine site (BZD) of the receptor was tested. α2-GABA ADuring the passage process of R-HEK293 cells, some suspended cells were seeded onto slides pretreated with poly-D-lysine (polylysine) and subjected to electrophysiological testing (see paragraph 0586 of patent CN107344936A for the method).

[0955] α2-GABA A Affinity activity of the compound of the present invention on receptors 3 H-flunitrazepam (isotope 3 Humanized α2-GABA competes with H-labeled flunitrazepam. A α2-GABA is released when a membrane protein stably expressed in R-HEK293 cells binds to the BZD site. A The affinity of the compound for the receptor was detected.

[0956] Membrane preparation: Cells were suspended in 50 mM Tris-HCl buffer (pH=7.4), homogenized 10 times for 20 seconds on ice, and centrifuged at 1000 g for 10 minutes at 4°C. The supernatant was removed and the above steps were repeated. The supernatant was centrifuged at 4°C (33800 g, Thermo, rotor: A27-8x50) for 60 minutes, and the pellet was resuspended in Tris buffer (50 mM Tris-HCl, 10 mM MgCl2, 0.5 mM EDTA, 10% glycerol). Protein content was measured (BCA (bicinchoninic acid) protein quantification test based on copper ion reduction, BCA kit purchased from Pierce (ANNORON)), 1 mL aliquots were prepared and stored at -80°C.

[0957] Radioactive ligand competitive binding test: This test was performed in a 200 μL system (96-well plate) containing 100 μL of cell membrane. 3 3 The concentration of H-flunitrazepam is 1 nM, and the concentration of the test compound is 1 × 10⁻⁶ -5 ~10 -6It was in the range of MM. Flumazenil (hereinafter referred to as flumazenil) was used as a control. 1 μL of 2 mM flumazenil (final concentration 10 μM) was added to the low signal control well (Low control, LC), and 1 μL of dimethyl sulfoxide was added to the high signal control well (High control, HC). The final concentration of the target membrane protein was 5 μg / well. All stock solutions of the test compound samples were 10 mM dimethyl sulfoxide solutions. The working concentrations of the samples were prepared by diluting all samples to 0.2 mM with dimethyl sulfoxide and then performing a four-fold serial dilution to create a total of eight concentration gradients. The 96-well plate was sealed with a sealing film and incubated on a shaker at room temperature for 1 hour. At the same time, the GF / C filter plate was immersed in plate dipping buffer (0.3% PEI (polyethyleneimine, purchased from Sigma-Aldrich, model: P314), stored at 4 °C) for at least 0.5 hours. After the binding incubation, cells were collected onto the GF / C filter plate using a cell harvester and washed four times with plate washing buffer (50 mM Tris-HCl, pH 7.4, stored at 4 °C). After drying in an oven at 50 °C for 1 hour, the bottom of the dried GF / C filter plate was sealed with a membrane, and the radioactivity remaining on the filter membrane was detected by liquid scintillation counting. 50 μL of scintillation fluid was added to each well, the well was sealed, and Microbeta 2 (Microplate Counter, purchased from PerkinElmer, model: CNLL0153) was used to read the data. 3 of the test samples 3 H-flunitrazepam and GABA A binding inhibitory activity to the receptor membrane protein was calculated, and the IC 50 of each test sample was calculated by dose-effect curve fitting (GraphPad Prism 5 software), and the K 50 of the sample was calculated based on the IC i to evaluate the binding ability of the compound to the BZD site of the α2-GABA A receptor. <00049​​​​Representative test results for determining the binding affinity of compounds to the BZD site of the R-HEK293 cell membrane protein are shown in Table 1.

[0959] GABA A Functional activity of the compounds of the present invention against different receptor subtypes The test drug α2-GABA A Positive regulatory activity towards the receptor was detected using electrophysiological methods. The specific method is as follows:

[0960] Compound concentration setting: The final concentration of all compounds used in compound screening was 100 nM. α2-GABA A In cell lines expressing the receptor, the GABA concentration is 0.10-0.11 μM (approximately EC2). 7~8 ). The whole-cell patch-clamp method was used for the electrophysiological test, and the method can be found in the literature (Nickolls, SA, et al. British Journal of Pharmacology, 2018, 175: 708-725). Composition of the extracellular solution (ECS) for electrophysiology: 150 mM NaCl, 5 mM KCl, 2.5 mM CaCl2, 1 mM MgCl2, 10 mM HEPES and 10 mM glucose (pH 7.4). Composition of the internal electrode solution (ICS) for electrophysiology: 140 mM CsCl, 11 mM EGTA, 10 mM HEPES, 2 mM CaCl2, 1 mM MgCl2, 4 mM MgATP and 2 mM TEA (pH 7.3). GABA (γ-aminobutyric acid) powder was prepared as a mother liquor with pure water and diluted with ECS. The compound was first prepared as a 4 mM mother liquor with dimethyl sulfoxide, and then gradually diluted to the corresponding concentration with GABA-ECS. All solutions were freshly prepared before electrophysiological testing.

[0961] Electrophysiological signals were obtained using an EPC 10 amplifier and PatchMaster software (HEKA), or an Axon 700B amplifier and Clampex software (AXON). The recording electrodes were made of borosilicate glass and had an electrode resistance of 4 - 6 MΩ. The ALA-VC-8PG® system was used for extracellular drug delivery. A single cell grown independently was selected, and after tightly sealing the glass electrode and the cell, the membrane was ruptured to form a whole-cell pattern. The cell membrane potential was clamped at -60 mV and recorded in Gap-free mode. During the experiment, first, the extracellular solution was applied to the outside of the cell for about 20 seconds. After the baseline (I prebaseline ) became stable, the extracellular solution was switched to GABA-ECS. At this time, the current (I gaba ) induced by GABA could be detected. After about 10 - 20 seconds, when the current became stable, the extracellular solution was switched to a mixed solution of the compound and GABA-ECS, and the process continued until the current (I treatment ) induced by the compound and GABA could be detected. Finally, the solution was switched back to the extracellular solution, recorded for 20 - 40 seconds, and then the experiment was terminated. Only cells with a relatively stable current within 10 - 20 seconds, where the absolute value of the stable baseline and the control current (I gaba -I prebaseline ) exceeded 40 pA, were used for the compound test.

[0962] α2-GABA A The experimental results of the positive allosteric regulation of R were analyzed using PatchMaster v2x90.1 or PatchMaster v2x90.3 (EPC 10 amplifier) and Clampex 10.6 software (Axon 700B amplifier). The current values at each stage were calculated based on the average value of the current after it became stable under the corresponding conditions. The control current was defined as I gaba -I prebaseline , and the current after compound treatment was defined as I treatment -I prebaseline . The allosteric regulatory activity of the compound was expressed as a percentage and calculated according to the following formula: Functional activity = [(I treatment -I gaba ) / (Igaba -I prebaseline )] × 100%. A negative value means that the test compound's modulation of the GABA receptor is negative allosteric modulation. A positive value means that the test compound's modulation of the GABA receptor is positive allosteric modulation. To facilitate comparison, the positive compound CVL-865 (i.e., Example 4 of WO2014091368A1) was normalized as the reference compound, i.e., positive allosteric modulation = [functional activity of the compound / functional activity of the reference compound] × 100%.

[0963] Affinity activity of each compound of the present invention toward receptors and α2-GABA A The positive allosteric regulatory activity on the receptor is shown in Table 1 below.

[0964] Furthermore, since the absolute value of the functional activity of a compound varies to some extent in different detection systems, making direct comparisons meaningless, for the convenience of comparison, in the experiments of this invention, the control compound and the related compound were detected simultaneously using the same detection system, and normalization was performed using the positive compound CVL-865 as a reference. That is, positive allosteric regulatory activity = [functional activity of the compound / functional activity of the reference compound] × 100%, and the specific results are shown in Table 1 below.

[0965] [Table 2] TIFF2026516799000204.tif246169TIFF2026516799000205.tif246169TIFF2026516799000206.tif246169TIFF2026516799 000207.tif246169TIFF2026516799000208.tif246169TIFF2026516799000209.tif246169TIFF2026516799000210.tif88169

[0966] The structures of the comparative compounds are shown below.

[0967]

change

Claims

1. Compounds represented by formula (I), their isotopic derivatives, their nitrogen oxides, their pharmaceutically acceptable salts, their solvates, or solvates of their pharmaceutically acceptable salts. 【Chemistry 1】 (however, R １ and R ２ are independently hydrogen, C １－６ alkyl, C ３－６ cycloalkyl, C ２－６ alkenyl, C ２－６ alkynyl, 4- to 12-membered heterocycloalkyl, C ６－１０ aryl, 5- to 12-membered heteroaryl, or C ９ substituted by 1, 2, 3, 4 or 5 R １－６ alkyl, C ３－６ cycloalkyl, C ２－６ alkenyl, C ２－６ alkynyl, 4- to 2-membered heterocycloalkyl, C ６－１０ aryl, 5- to 12-membered heteroaryl, and Or, R １ and R ２ These are N atoms linked to them and 4-12 member heterocycloalkyl groups, or 1, 2, or 3 R atoms. １－１ Forms a 4- to 12-membered heterocycloalkyl group substituted with R １－１ These are independently deuterium, -CN, -OH, halogen, and C １－６ Alkyl or -O-C １－６ It is alkyl, R ３ and R ４ H, C １－６ Alkyl, C ３－６ Cycloalkyl, -O-C １－６ Alkyl or 1, 2, or 3 R ３－１ C replaced by １－６ Alkyl, C ３－６ Cycloalkyl, -O-C １－６ It is alkyl, R ３－１ These are independently deuterium, -CN, -OH, halogen, and C １－６ Alkyl or -O-C １－６ It is alkyl, R ５ and R ６ These are independently hydrogen, deuterium, halogen, or C １－６ It is alkyl, X is N or CR ８ And, R ８ is hydrogen, deuterium, halogen, -CN, C １－６ Alkyl, C ３－６ Cycloalkyl, -O-C １－６ Alkyl, or 1, 2, or 3 R ８－１ C replaced by １－６ Alkyl, C ３－６ Cycloalkyl, -O-C １－６ It is alkyl, R ８－１ These are independently deuterium, -CN, -OH, halogen, and C １－６ Alkyl or -O-C １－６ It is alkyl, R ７ Ha-CN, C １－６ Alkyl, C ３－６ Cycloalkyl, C ３－６ Cycloalkenyl, C ６－１０ Aryl, 5-12 member heteroaryl, 5-12 member heterocycloalkyl, 5-12 member heterocycloalkenyl, -Z-(CR ａ R ｂ ) ｍ -C ６－１０ Ariel, -Z- (CR ａ R ｂ ) ｍ - 5 to 12-membered heteroaryl, or 1, 2, 3, 4 or 5 R １０ C replaced by １－６ Alkyl, C ３－６ Cycloalkyl, C ３－６ Cycloalkenyl, C ６－１０ Aryl, 5-12 member heteroaryl, 5-12 member heterocycloalkyl, 5-12 member heterocycloalkenyl, -Z-(CR ａ R ｂ ) ｍ -C ６－１０ Ariel, -Z- (CR ａ R ｂ ) ｍ -5 to 12 member heteroaryls, Z is independently -O- or -NR ｃ And R ａ and R ｂ H or C １－６ It is alkyl, R ｃ is H or C １－６ It is alkyl, m is independently 0, 1, or 2. R ９ is halogen, -OH, -CN, C １－６ Alkyl, -O-C １－６ Alkyl, C ３－６ Cycloalkyl, 5-12 member heterocycloalkyl, C ６－１０ Aryl or 5- to 12-membered heteroaryl, or 1, 2 or 3 R ９－１ C replaced by １－６ Alkyl, -O-C １－６ Alkyl, C ３－６ Cycloalkyl, 5-12 member heterocycloalkyl, C ６－１０ It is an aryl or a 5- to 12-membered heteroaryl, R ９－１ These are independently deuterium, -CN, -OH, halogen, and C １－６ Alkyl or -O-C １－６ It is alkyl, R １０ is oxo (–C=O), deuterium, halogen, –OH, –CN, 【Chemistry 2】 , C １－６ alkyl, C ２－６ alkenyl, C ２－６ alkynyl, -O-C １－６ alkyl, -S-C １－６ alkyl, C ６－１０ aryl, 5- to 12-membered heteroaryl, C ３－６ cycloalkyl, 5- to 12-membered heterocycloalkyl, or C substituted by 1, 2, 3, 4 or 5 Rs １１ alkyl, C １－６ alkyl, C ２－６ alkenyl, C ２－６ alkynyl, -O-C １－６ alkyl, -S-C １－６ alkyl, C ６－１０ aryl, 5- to 12-membered heteroaryl, C ３－６ cycloalkyl, 5- to 12-membered heterocycloalkyl, and R １１ Deuterium, halogen, -CN, -OH, C １－６ Alkyl, -O-C １－６ Alkyl or oxo (-C=O), Each of the 5- to 12-membered heteroaryls is independently a 5- to 12-membered heteroaryl having one, two, three, or four heteroatoms, and the type of heteroatom is independently selected from N, O, and S. Each of the 4- to 12-membered heterocycloalkyls is independently a 4- to 12-membered heterocycloalkyl having one, two, three, or four heteroatoms, and the type of heteroatom is independently selected from N, O, and S. Each of the 5- to 12-membered heterocycloalkyls is independently a 5- to 12-membered heterocycloalkyl having one, two, three, or four heteroatoms, and the type of heteroatom is independently selected from N, O, and S. Each of the 5- to 12-membered heterocycloalkenyls is independently a 5- to 12-membered heterocycloalkenyl having one, two, three, or four heteroatoms, and the type of heteroatom is independently selected from N, O, and S.

2. A compound represented by formula (I) as described in claim 1, an isotopic derivative thereof, a nitrogen oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof. 【Transformation 3】 (however, R １ and R ２ Hydrogen and C are independent of each other. １－６ Alkyl, C ３－６ Cycloalkyl, C ２－６ Alkenil, C ２－６ Alkynyl, 5-12 member heterocycloalkyl, C ６－１０ Aryl, 5-12 member heteroaryl, or 1, 2, 3, 4 or 5 R ９ C replaced by １－６ Alkyl, C ３－６ Cycloalkyl, C ２－６ Alkenil, C ２－６ Alkynyl, 5-12 member heterocycloalkyl, C ６－１０ Aryl, 5-12 member heteroaryl, Or, R １ and R ２ These form 5-12 member heterocycloalkyl groups with the N atoms linked to them. R ３ and R ４ H is, R ５ and R ６ These are independently hydrogen or methyl, X is N or CR ８ And, R ８ is hydrogen, deuterium, halogen, -CN, methoxy, methyl or -CHF ２ And, R ７ Ha-CN, C １－６ Alkyl, C ３－６ Cycloalkyl, C ３－６ Cycloalkenyl, C ６－１０ Aryl, 5-12 member heteroaryl, 5-12 member heterocycloalkyl, 5-12 member heterocycloalkenyl, -Z-(CR ａ R ｂ ) ｍ -C ６－１０ A aryl, or 1, 2, 3, 4, or 5 R's １０ C replaced by １－６ Alkyl, C ３－６ Cycloalkyl, C ３－６ Cycloalkenyl, C ６－１０ Aryl, 5-12 member heteroaryl, 5-12 member heterocycloalkyl, 5-12 member heterocycloalkenyl, -Z-(CR ａ R ｂ ) ｍ -C ６－１０ It is Ariel, Z is -O- or -NR ｃ And R ａ and R ｂ H or C １－６ It is alkyl, R ｃ is H or C １－６ It is alkyl, m is 0, 1, or 2. R ９ is halogen, -OH, -CN, C １－６ Alkyl, -O-C １－６ Alkyl, C ３－６ Cycloalkyl, 5-12 member heterocycloalkyl, C ６－１０ It is an aryl or a 5- to 12-membered heteroaryl. R １０ is oxo (-C=O), deuterium, halogen, hydroxyl, -CN, 【Chemistry 4】 , C １－６ Alkyl, C ２－６ Alkinyl, -O-C １－６ Alkyl, -S-C １－６ Alkyl, 5-12 member heteroaryl, C ３－６ Cycloalkyl, 5-12 member heterocycloalkyl, or 1, 2, 3, 4 or 5 R １１ C replaced by １－６ Alkyl, C ２－６ Alkinyl, -O-C １－６ Alkyl, -S-C １－６ Alkyl, 5-12 member heteroaryl, C ３－６ They are cycloalkyl and 5-12 member heterocycloalkyl. R １１ is halogen, -CN, -OH, C １－６ Alkyl or oxo (-C=O), Each of the 5-12 member heteroaryls is independently a 5-12 member heteroaryl having one, two, or three heteroatoms, and the type of heteroatom is independently selected from N, O, and S. Each of the 5-12 member heterocycloalkyls is independently a 5-12 member heterocycloalkyl having one, two, or three heteroatoms, and the type of heteroatom is independently selected from N, O, and S. Each of the 5-12 member heterocycloalkenyls is independently a 5-12 member heterocycloalkenyl having one, two, or three heteroatoms, and the type of heteroatom is independently selected from N, O, and S.

3. A compound represented by formula (I) as described in claim 1, an isotope derivative thereof, a nitrogen oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that it satisfies one or more of the following conditions: (1) R １ The condition is that H (2) R ２ is C １－６ Alkyl, C ３－６ Cycloalkyl, C ２－６ Alkenil, C ２－６ Alkynyl, 4-12 member heterocycloalkyl, C ６－１０ Aryl, 5-12 member heteroaryl, or 1, 2, 3, 4 or 5 R ９ C replaced by １－６ Alkyl, C ３－６ Cycloalkyl, C ２－６ The conditions are that the alkenyl, 4-12 member heterocycloalkyl, or 5-12 member heteroaryl, (3) Caution １－１ is C １－６ Conditions for being alkyl, (4) R ３ and R ４ The condition is that H (5) Note ８ is hydrogen, deuterium, halogen, -CN, C １－６ Alkyl, -O-C １－６ Alkyl or 1, 2, or 3 R ８－１ C replaced by １－６ Conditions for being alkyl, (6) R ７ Ha-CN, C １－６ Alkyl, C ３－６ Cycloalkenyl, or 1, 2, 3, 4 or 5 R １０ C replaced by ６－１０ Aryl, 5-12 member heteroaryl, 5-12 member heterocycloalkyl, 5-12 member heterocycloalkenyl, -Z-(CR ａ R ｂ ) ｍ -C ６－１０ Conditions for being aryl, (7) R ａ and R ｂ The condition is that H (8) The condition that Z is -O-, (9) The condition that m is 0 or 1, (10) R ９ is halogen, -OH, -CN, C １－６ Alkyl, -O-C １－６ Alkyl, C ３－６ Cycloalkyl, 5-12 member heterocycloalkyl, C ６－１０ Aryl or 5- to 12-membered heteroaryl, or 1, 2 or 3 R ９－１ The condition is that it is a 5- to 12-membered heteroaryl substituted by, (11) R ９－１ C is independent １－６ Conditions for being alkyl, (12) R １０ oxo (-C=O), deuterium, halogen, -OH, -CN, 【Transformation 5】 , C １－６ Alkyl, C ２－６ Alkinyl, -O-C １－６ Alkyl, -S-C １－６ Alkyl, 5-12 member heteroaryl, C ３－６ Cycloalkyl, 5-12 member heterocycloalkyl, or 1, 2, 3, 4 or 5 R １１ C replaced by １－６ Alkyl, C ２－６ Alkinyl, -O-C １－６ Alkyl, -S-C １－６ Alkyl, 5-12 member heteroaryl, C ３－６ Conditions for being a cycloalkyl or a 5-12 membered heterocycloalkyl, and (13) R １１ Deuterium, halogen, -CN, -OH, C １－６ The condition is that it is alkyl or oxo (-C=O).

4. A compound represented by formula (I) as described in claim 1, an isotope derivative thereof, a nitrogen oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that it satisfies one or more of the following conditions: (1) R １ , R ２ , R ３ , R ４ , R ５ , R ６ , R ７ , R ８ , R ９ , R １０ , R １１ , R １－１ , R ３－１ , R ８－１ , R ９－１ , R ａ and R ｂ And the aforementioned C １－６ Alkyl and substituted C １－６ C in alkyl １－６ The alkyl group is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or tert-butyl. (2) R １ , R ２ , R ３ , R ４ , R ７ , R ８ , R ９ and R １０ And the aforementioned C ３－６ Cycloalkyl and substituted C ３－６ C in cycloalkyl ３－６ Cycloalkyls are independently cyclopropyl, cyclobutyl, cyclopentyl, 【Transformation 6】 Or, under the condition that it is cyclohexyl, (3) Caution １ , R ２ and R １０ And the aforementioned C ２－６ Alkenyl and substituted C ２－６ C in alkenyl ２－６ The alkenyl is independently vinyl, n-propenyl, isopropenyl, n-butenyl, or isobutenyl. (4) R １ , R ２ and R １０ And the aforementioned C ２－６ Alkynyl and substituted C ２－６ C in alkinyl ２－６ Alkynyl is independently ethynyl, n-propynyl, or n-butynyl. (5) Note １ , R ２ , R ７ , R ８ , R ９ , R １０ and R １１ And the aforementioned C ６－１０ Aryl and substituted C ６－１０ C in Arley ６－１０ The condition is that the aryl is independently phenyl or naphthyl. (6) R ３ , R ４ , R ８ , R ９ , R １０ , R １１ , R １－１ , R ３－１ , R ８－１ and R ９－１ And the above-O-C １－６ Alkyl and substituted -O-C １－６ C in alkyl １－６ The alkyl group is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or tert-butyl. (7) R ３ , R ４ , R ５ , R ６ , R ８ , R ９ , R １０ , R １１ , R １－１ , R ３－１ , R ８－１ and R ９－１ And the halogen is independently F, Cl, or Br, (8) R １ and R ２ The 4-12 member heterocycloalkyl group and 1, 2, 3, 4 or 5 R groups. ９ In a 4-12 member heterocycloalkyl group substituted by the condition that each 4-12 member heterocycloalkyl group is independently a 4-6 member heterocycloalkyl group, (9) Caution １ and R ２ The 4-12 member heterocycloalkyl group and 1, 2, 3, 4 or 5 R groups. ９ In a 4-12 member heterocycloalkyl substituted by, each 4-12 member heterocycloalkyl independently has one, two, or three heteroatoms, and the type of heteroatom is N, (10) R １ and R ２ The 5-12 member heteroaryl and 1, 2, 3, 4 or 5 R ９ In a 5-12 member heteroaryl substituted by the condition that each 5-12 member heteroaryl is independently a 5-6 member heteroaryl, (11) R １ and R ２ The 5-12 member heteroaryl and 1, 2, 3, 4 or 5 R ９ In a 5-12 membered heteroaryl substituted by, each 5-12 membered heteroaryl independently has one, two, or three heteroatoms, and the type of heteroatom is selected from N and O, and the condition is that it is a 5-12 membered heteroaryl. (12) R １ and R ２ These consist of an N atom linked to them and a 4-12 member heterocycloalkyl group or 1, 2, or 3 R atoms. １－１ When forming a 4- to 12-membered heterocycloalkyl group substituted with, the 4- to 12-membered heterocycloalkyl group and 1, 2 or 3 R １－１ In a 4-12 member heterocycloalkyl group substituted by the condition that each 4-12 member heterocycloalkyl group is independently a 4-6 member heterocycloalkyl group, (13) R １ and R ２ These are N atoms linked to them and 4-12 member heterocycloalkyl groups, or 1, 2, or 3 R groups. １－１ When forming a 4- to 12-membered heterocycloalkyl group substituted with R, the 4- to 12-membered heterocycloalkyl group and 1, 2, or 3 R １－１ In a 4-12 member heterocycloalkyl substituted by, each 4-12 member heterocycloalkyl independently has one, two, or three heteroatoms, and the type of heteroatom is N, (14) R ７ And the aforementioned C ３－６ Cycloalkenyl and 1, 2, 3, 4 or 5 R １０ C replaced by ３－６ C in cycloalkenyls ３－６ Cycloalkenyls are independently cyclopropenyl, cyclobutenyl, cyclopentenyl, or cyclohexenyl. (15) R ７ The 5-12 member heteroaryl and 1, 2, 3, 4 or 5 R １０ In a 5-12 membered heteroaryl substituted by, each 5-12 membered heteroaryl independently has one, two, or three heteroatoms, and the type of heteroatom is selected from N and O, thus it is a 5-12 membered heteroaryl. (16) R ７ The 5-12 member heterocycloalkyl group and 1, 2, 3, 4 or 5 R groups. １０ In a 5-12 member heterocycloalkyl group substituted by the condition that each 5-12 member heterocycloalkyl group is independently a 5-6 member heterocycloalkyl group, (17) R ７ The 5-12 member heterocycloalkyl group and 1, 2, 3, 4 or 5 R groups. １０ In a 5-12 member heterocycloalkyl substituted by, each 5-12 member heterocycloalkyl independently has one, two, or three heteroatoms, and the type of heteroatom is selected from N and O, under the condition that it is a 5-12 member heterocycloalkyl. (18) R ７ The 5-12 member heterocycloalkenyl and 1, 2, 3, 4 or 5 R １０ In 5-12 member heterocycloalkenyls substituted by the condition that each 5-12 member heterocycloalkenyl is independently a 5-6 member heterocycloalkyl, (19) R ７ The 5-12 member heterocycloalkenyl and 1, 2, 3, 4 or 5 R １０ In 5-12 member heterocycloalkenyls substituted by, each 5-12 member heterocycloalkenyl independently has one, two, or three heteroatoms, and the heteroatom type is N, which is a condition for being a 5-12 member heterocycloalkyl. (20) R ７ And the above-Z-(CR ａ R ｂ ) ｍ -C ６－１０ aryl, and 1, 2, 3, 4 or 5 R １０ -Z-(CR) ａ R ｂ ) ｍ -C ６－１０ -Z-(CR) in Aryl ａ R ｂ ) ｍ -C ６－１０ Ariel is independent 【Transformation 7】 The condition, (21) R ９ Therefore, the 5-12 member heteroaryl and 1, 2 or 3 R ９－１ In a 5-12 member heteroaryl substituted by the condition that each 5-12 member heteroaryl is independently a 5-6 member heteroaryl, (22) R ９ Therefore, the 5-12 member heteroaryl and 1, 2 or 3 R ９－１ In a 5-12 membered heteroaryl substituted by, each 5-12 membered heteroaryl independently has one, two, or three heteroatoms, and the type of heteroatom is selected from N and O, thus it is a 5-12 membered heteroaryl. (23) R １０ Therefore, the 5-12 member heteroaryl and 1, 2 or 3 R ９－１ In a 5-12 member heteroaryl substituted by, each 5-12 member heteroaryl independently has one, two, three, or four heteroatoms, and the type of heteroatom is selected from N and O, thus it is a 5-12 member heteroaryl. (24) R １０ The 5-12 member heterocycloalkyl group and 1, 2, or 3 R groups. ９－１ In a 5-12 member heterocycloalkyl group substituted by the condition that each 5-12 member heterocycloalkyl group is independently a 5-6 member heterocycloalkyl group, (25) R １０ The 5-12 member heterocycloalkyl group and 1, 2, or 3 R groups. ９－１ In a 5-12 member heterocycloalkyl substituted by, each 5-12 member heterocycloalkyl independently has one, two, or three heteroatoms, and the type of heteroatom is selected from N and O, under the condition that it is a 5-12 member heterocycloalkyl. (26) R １０ And the above-S-C １－６ Alkyl and 1, 2, 3, 4 or 5 R １１ -S-C substituted by １－６ C in alkyl １－６ The alkyl group is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or tert-butyl.

5. A compound represented by formula (I) as described in claim 1, an isotope derivative thereof, a nitrogen oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that it satisfies one or more of the following conditions: (1) R １ , R ２ , R ３ , R ４ , R ５ , R ６ , R ７ , R ８ , R ９ , R １０ , R １１ , R １－１ , R ３－１ , R ８－１ , R ９－１ , R ａ and R ｂ And the aforementioned C １－６ Alkyl and substituted C １－６ C in alkyl １－６ The alkyl group is independently methyl, ethyl, n-propyl, or isopropyl. (2) R １ , R ２ , R ７ , R ８ , R ９ , R １０ and R １１ And the aforementioned C ６－１０ Aryl and substituted C ６－１０ C in Arley ６－１０ The condition is that aryl is independently phenyl. (3) Caution ３ , R ４ , R ８ , R ９ , R １０ , R １１ , R １－１ , R ３－１ , R ８－１ and R ９－１ And the above-O-C １－６ Alkyl and substituted -O-C １－６ C in alkyl １－６ The alkyl group is independently methyl, ethyl, n-propyl, or isopropyl. (4) R ３ , R ４ , R ５ , R ６ , R ８ , R ９ , R １０ , R １１ , R １－１ , R ３－１ , R ８－１ and R ９－１ And the halogen is independently F or Cl, (5) Note １ and R ２ The 4-12 member heterocycloalkyl group and 1, 2, 3, 4 or 5 R groups. ９ In the 4-12 member heterocycloalkyl groups substituted by, the 4-12 member heterocycloalkyl groups are independently 【Transformation 8】 The condition, (6) R １ and R ２ The 5-12 member heteroaryl and 1, 2, 3, 4 or 5 R ９ In the 5-12 member heteroaryls substituted by, the 5-12 member heteroaryls are independently 【Chemistry 9】 The condition, (7) R １ and R ２ These are N atoms linked to them and 4-12 member heterocycloalkyl groups, or 1, 2, or 3 R groups. １－１ When forming a 4- to 12-membered heterocycloalkyl group substituted with, the 4- to 12-membered heterocycloalkyl group and 1, 2 or 3 R １－１ In the 4-12 member heterocycloalkyl groups substituted by, the 4-12 member heterocycloalkyl groups are independently 【Chemistry 10】 The condition, (8) R ７ And the aforementioned C ３－６ Cycloalkenyl and 1, 2, 3, 4 or 5 R １０ C replaced by ３－６ C in cycloalkenyls ３－６ Cycloalkenyls 【Chemistry 11】 The condition, (9) Caution ７ The 5-12 member heteroaryl and 1, 2, 3, 4 or 5 R １０ In the 5-12 member heteroaryls substituted by, the 5-12 member heteroaryls are independently 【Chemistry 12】 The condition, (10) R ７ The 5-12 member heterocycloalkyl group and 1, 2, 3, 4 or 5 R groups. １０ In the 5-12 member heterocycloalkyl groups substituted by, the 5-12 member heterocycloalkyl groups are independently 【Chemistry 13】 The condition, (11) R ７ The 5-12 member heterocycloalkenyl and 1, 2, 3, 4 or 5 R １０ In 5-12 member heterocycloalkenyls substituted by, the 5-12 member heterocycloalkenyls are independently 【Chemistry 14】 The condition, (12) R ９ Therefore, the 5-12 member heteroaryl and 1, 2 or 3 R ９－１ In the 5-12 member heteroaryls substituted by, the 5-12 member heteroaryls are independently 【Chemistry 15】 The condition, (13) R １０ Therefore, the 5-12 member heteroaryl and 1, 2 or 3 R ９－１ In the 5-12 member heteroaryls substituted by, the 5-12 member heteroaryls are independently 【Chemistry 16】 The condition, (14) R １０ The 5-12 member heterocycloalkyl group and 1, 2, or 3 R groups. ９－１ In the 5-12 member heterocycloalkyl groups substituted by, the 5-12 member heterocycloalkyl groups are independently 【Chemistry 17】 The conditions for being, (15) R １０ And the above-S-C １－６ Alkyl and 1, 2, 3, 4 or 5 R １１ -S-C substituted by １－６ C in alkyl １－６ The condition is that alkyl is independently methyl.

6. A compound represented by formula (I) as described in claim 1, an isotope derivative thereof, a nitrogen oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that it satisfies one or more of the following conditions: (1) R ２ teeth [Chemistry 18] And, Or, R １ and R ２ They are linked to the N atom and 【Chemistry 19】 Conditions for forming (2) R ５ The condition is that it is H, deuterium, or methyl. (3) Caution ６ The condition is that it is H, deuterium, F, or methyl. (4) R ７ teeth 【Chemistry 20】 【change】 The conditions for being, (5) Note ８ H, D, F, Cl, -CN, -CH ３ , -OCH ３ or -CHF ２ The condition for this to be true.

7. A compound represented by formula (I) as described in claim 1, an isotope derivative thereof, a nitrogen oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that it satisfies one or more of the following conditions: （１） 【Chemistry 21】 teeth 【Chemistry 22】 The condition, (2) R ９ F, -OH, -CN, methyl, methoxy, cyclopropyl, phenyl, 【Chemistry 23】 The condition is, (3) R １０ oxo (-C=O), deuterium, F, Cl, -OH, -CN, 【Chemistry 24】 methyl, methoxy, -CF ３ , 【Chemistry 25】 The conditions for being, (4) R １１ is deuterium, F, -CN, methyl, ethyl, or oxo (-C=O), Preferably, 【Chemistry 26】 teeth 【Chemistry 27】 (for example, 【Chemistry 28】 ) and R ７ teeth 【Chemistry 29】 The condition for this to be true.

8. The compound represented by formula (I) according to claim 1, an isotope derivative thereof, a nitrogen oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that the compound represented by formula (I) is selected from any one of the following compounds. Table 1

9. A pharmaceutical composition comprising substance X and a pharmaceutical adjuvant, wherein substance X is a compound according to any one of claims 1 to 8, an isotopic derivative thereof, a nitrogen oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof.

10. GABA Ａ Use of substance X or the pharmaceutical composition according to claim 9 in the manufacture of a pharmaceutical for treating or preventing receptor-related diseases, wherein substance X is a compound according to any one of claims 1 to 8, an isotopic derivative thereof, a nitrogen oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof.

11. GABA Ａ The use of substance X according to claim 10 or the pharmaceutical composition according to claim 9 in the manufacture of a pharmaceutical for treating or preventing receptor-related diseases, wherein the GABA Ａ Receptor-related disorders are selected from pain, Alzheimer's disease, multiple infarct dementia, stroke, epilepsy, anxiety, pruritus, and depression, and used accordingly.

12. GABA Ａ The use of substance X according to claim 10 or the pharmaceutical composition according to claim 9 in the manufacture of a pharmaceutical for treating or preventing receptor-related diseases, wherein the GABA Ａ Receptor-related diseases are associated with α2 / 3-GABA Ａ It is used for receptor-related disorders, such as pain, epilepsy, anxiety, itching, and depression.

13. Use of substance X according to claim 10 or the pharmaceutical composition according to claim 9 in the manufacture of a pharmaceutical, wherein the pharmaceutical is used for the treatment or prevention of pain, Alzheimer's disease, multiple infarct dementia, stroke, pain, epilepsy, anxiety, itching, or depression.

Images