ABCA derivative as well as precursor, preparation method and application thereof

Abstract

The invention provides an ABCA derivative as well as a precursor, a preparation method and application thereof. The structure of the ABCA derivative is as shown in the following formula III-1, III-2 or III-3, iII < I-2 >; and III <-3 >. The ABCA derivative is prepared from a tricyclic compound, and the structure of the tricyclic compound is as shown in formula I, wherein n is a positive integer from 0 to 2; r1 is any one of CH and N; r2 is any one of H, an amino protecting group and a substituted or unsubstituted carboxyl group, wherein the substituted group is a C1-C10 alkyl group; according to the synthesis method, the limitation of a traditional method is solved, a powerful framework is provided for expanding the diversity of an ABCA library, and a new possibility is developed for designing a therapeutic agent with higher selectivity and curative effect. The ABCA derivative has the potential of being developed into a medicine, and is particularly used for developing an orexin receptor antagonist and a biological isovolumetric compound.

Description

Technical Field

[0001] This invention relates to the field of chemical synthesis technology, specifically to an ABCA derivative and its precursor, preparation method, and application. Background Technology

[0002] Bridging compounds, such as cubane, adamantane, and bicyclic [xyz]alkanes, have attracted considerable interest in the fields of chemistry and medicinal chemistry due to their physicochemical and pharmacological advantages in drug discovery. Among them, azabicyclic [x,1,1]alkanes, with their azabicyclic butyl sequence, have become a cornerstone of medicinal chemistry due to their additional structural and functional properties derived from the nitrogen atom. These molecules are characterized by an inherent ring strain, which imposes a rigid and well-defined geometry, enhancing target selectivity and bioactivity. For example, Selpercatinib, approved in 2020 for the treatment of cancers with RET gene alterations, contains 3,6-diazabicyclic [3.1.1]heptane. This structural component contributes to its high selectivity and potency against target proteins by providing a well-defined geometry. Furthermore, the azabicyclic motif possesses favorable physical properties that significantly influence the pharmacokinetic profile of candidate drugs. For instance, molecule AB801, a novel, highly potent, selective, and orally bioavailable AXL inhibitor, is currently in Phase 1 clinical trials. The use of the oxazabicyclo[3.1.1]heptyl sequence in AB801 improved its potency and PK properties, exhibiting lower in vivo rat clearance, significantly higher oral exposure, and moderate bioavailability.

[0003] ABCA (Azabicyclo[x,1,1]alkanes) motifs have been widely used as bioequivalents to the most commonly used rings in drug development, such as benzene and piperazine. However, previous optimization efforts have primarily focused on bioequivalent substitution, with limited exploration of further optimization involving modifications to the bicyclic scaffold itself. This lack of representativeness is mainly due to significant synthetic challenges, particularly in achieving a variety of functional groups at the molecular bridging position. Traditional synthetic routes for ABCAs involve intramolecular cyclization. This approach begins with a monocyclic precursor and forms a bicyclic structure via intramolecular cyclization, typically through nucleophilic substitution or CH bond activation. However, introducing substituents at the bridging position of ABCAs is largely limited to the early stages of synthesis. Furthermore, while microbial hydroxylation of certain azabicycloalkanes has been achieved, this approach is limited to specific ring systems and is generally yield-low. These limitations highlight the challenge of expanding the range of ABCA substitutions, thus hindering their full potential in drug development. Summary of the Invention

[0004] To address the aforementioned problems, the present invention aims to provide an ABCA derivative, its precursor, preparation method, and application.

[0005] The objective of this invention is achieved through the following technical solution: In a first aspect, the present invention provides a tricyclic compound, the structure of which is shown in Formula I: I; Wherein, n is a positive integer from 0 to 2; R1 is any one of CH or N; R2 is any one of H, an amino protecting group, or a substituted or unsubstituted carboxyl group, wherein the substituted group is a C1-C10 alkyl group.

[0006] Where n is a positive integer from 0 to 2; Preferably, R1 is any one of CH and N; R2 is H, Cbz, Boc, COOMe, or COO. i Any of the following in Pr.

[0007] More preferably, R1 is CH, and R2 is H, COOMe, or COO. i Any of Pr; or R1 is N, and R2 is any of Cbz and Boc.

[0008] Secondly, the present invention provides an intermediate compound a, the structure of which is shown in Formula II-1: II-1; Wherein, n is a positive integer from 0 to 2; R1 is any one of CH and N; R2 is any one of H, amino protecting group, substituted or unsubstituted carboxyl group, wherein the substituted group is a C1-C10 alkyl group; R3, R4, and R5 are any one of the following 1)-4): 1) R3 is OH, and R4 and R5 are bonded to form an epoxy group (-O-); 2) R3 and R4 are both OH or OMs, and R5 is N3 or NH2; 3) R3 and R5 are both OH or OMs, and R4 is N3; 4) R3 and R4 are connected to form -N=PPh3- or -NH-, and R5 is OMs.

[0009] Thirdly, the present invention provides an intermediate compound b, the structure of which is shown in formula II-2, II-3, II-4 or II-5: II-2; II-3; II-4; II-5; In formula II-2, when n=1, R1 is CH and R2' is a substituted or unsubstituted carboxyl group, wherein the substituted group is a C1-C10 alkyl group; or when R1 is N, R2' is Cbz. When n=0 or 2, R1 is CH and R2 is H.

[0010] Preferably, in formula II-2, when n=1, R1 is CH and R2' is COOMe or COO. i Pr; or when R1 is N, R2' is Cbz.

[0011] Fourthly, the present invention provides a method for preparing a tricyclic compound comprising the following steps: A1. The compound shown in Formula II-2 is reacted with mCPBA to obtain an intermediate compound a, in which R3 is OH and R4 and R5 are connected to form an epoxy group (-O-), which is called compound a-1; A2. Compound a-1 is subjected to a ring-opening reaction with KN3 to obtain intermediate compound a with R3 and R4 both being OH and R5 being N3, or intermediate compound a with R3 and R5 both being OH and R4 being N3, which is called compound a-2. A3. Compound a-2 is subjected to methanesulfonation to obtain intermediate compound a with R3 and R4 both being OMs and R5 being N3, or intermediate compound a with R3 and R5 both being OMs and R4 being N3, which is called compound a-3. A4. Reaction of compound a-3 with PPh3 yields compound a, which is an intermediate of OMs, with R3 and R4 linked together to form -N=PPh3- and R5 being an intermediate of OMs. This compound is called compound a-4. Then, compound a-4 is reacted with t-BuOK to obtain the corresponding tricyclic compound shown in Formula I. Alternatively, reaction of compound a-4 with a strong base yields compound a, which is an intermediate of OMs, with R3 and R4 linked together to form -NH- and R5 being an intermediate of OMs. This compound is called compound a-5. Then, compound a-5 is reacted with t-BuOK to obtain the corresponding tricyclic compound shown in Formula I. A5. Compound a-3 is hydrogenated to obtain intermediate compound a, in which R3 and R4 are both OMs and R5 is NH2, or intermediate compound a, in which R3 and R5 are both OMs and R4 is NH2, is called compound a-6; then compound a-6 is reacted with PhLi to obtain the corresponding tricyclic compound shown in Formula I.

[0012] Preferably, the compound shown in Formula II-3 is reacted with a salt containing an amino protecting group to obtain the compound shown in Formula II-2, where n=1, R1 is N, and R2' is an amino protecting group; or The compound shown in Formula II-4 is reacted with DBU to produce the compound shown in Formula II-5. Then, the compound shown in Formula II-5 is reacted with an alcohol to give the compound shown in Formula II-2, where n=1, R1 is C, and R2' is a substituted or unsubstituted carboxyl group.

[0013] More preferably, the salt containing the amino protecting group includes, but is not limited to, CbzCl.

[0014] The alcohols include, but are not limited to, methanol and isopropanol.

[0015] Fourthly, the present invention provides an application of the aforementioned tricyclic compound in the preparation of ABCA derivatives. Based on the aforementioned tricyclic compound, various ABCA derivatives, including ABCA derivatives with known structures or ABCA derivatives with novel structures, can be prepared.

[0016] Fifthly, the present invention provides an ABCA derivative, the structure of which is shown in formula III-1, III-2 or III-3 as follows: III-1; III-2; III-3; Where n is a positive integer from 0 to 2; R6 is an amino protecting group; The groups of R7 and R8 are as follows: when R7 is CH, R8 is H, a substituted or unsubstituted ester group, a substituted or unsubstituted carboxyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted hydroxyl group; when R7 is N, R8 is an amino protecting group or a substituted or unsubstituted aryl group. R9 is any one of H or its isotopes, halogens, substituted or unsubstituted amides, substituted or unsubstituted alkyl groups, substituted or unsubstituted hydroxyl groups, substituted or substituted N heterocycles, substituted or substituted amino groups, alkyl sulfides, aryl sulfides, alkylamines, arylamines, and selenium. R10 is any one of substituted or unsubstituted aromatic rings, substituted or unsubstituted amides, substituted or unsubstituted N-heterocycles, substituted or unsubstituted amino groups, and substituted or unsubstituted alkyl groups; R11 and R12 are both NO2.

[0017] Preferably, the structure shown in Formula III-2 has an excellent exo-configuration.

[0018] Preferably, in formula III-1, III-2 or III-3, R6 is any one of Cbz, Boc, Ac, and Tos; The groups of R7 and R8 are: when R7 is CH, R8 is H, COOMe, or COO. iAny of Pr; when R7 is N, R8 is any of Cbz, Boc, and Ar; wherein Ar is or ; R9 represents D, halogen, CN, CH(CH3)2, OAc, OBoc, OMe, O(CH2)3Ph, OPh, OBz, OPO(OBn)2. , ,S(CH2)5 CH3,SePh,N3,NHBn, , NHPh, OH, NO2, OCHO O(CH2)4Cl N = PPh3, NH2 Any one of them; R10 is , , , , , , NHTOS , , ,NHPh Me Any one of them; R11 and R12 are both NO2.

[0019] Sixthly, the present invention provides a method for preparing root ABCA derivatives, comprising the following steps: B1. Substitute the tricyclic compound of claim 3 to obtain the ABCA derivative shown in formula III-1; B2. The ABCA derivative shown in Formula III-1 is subjected to a stereoselective transition metal catalytic reaction to obtain the ABCA derivative shown in Formula III-2; during the reaction, compound SI-92 or SI-93 is added. B3. Nitrogenate the ABCA derivative shown in Formula III-1 (react with sodium nitrite) to obtain the ABCA derivative shown in Formula III-3.

[0020] In a seventh aspect, the present invention provides the use of ABCA derivatives in the preparation of orexin receptor (OXR) antagonists or azatidine biosteroids or bioisosomes.

[0021] Eighthly, the present invention provides an orexin receptor (OXR) antagonist, the structure of which is shown in formula IV-1 or IV-2 below: IV-1; IV-2; Where n is a positive integer from 0 to 2; The groups of R7 and R8 are: when R7 is CH, R8 is H, COOMe, or COO. i Any of the following in Pr; when R7 is N, R8 is C. The groups of R7 and R8 are: when R7 is CH, R8 is H, a substituted or unsubstituted ester group, a substituted or unsubstituted carboxyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted hydroxyl group; when R7 is N, R8 is an amino protecting group or a substituted or unsubstituted aryl group. R9 is any one of H or its isotopes, halogens, substituted or unsubstituted amides, substituted or unsubstituted alkyl groups, substituted or unsubstituted hydroxyl groups, substituted or substituted N heterocycles, substituted or substituted amino groups, alkyl sulfides, aryl sulfides, alkylamines, arylamines, and selenium. R10 is any one of substituted or unsubstituted aromatic rings, substituted or unsubstituted amides, substituted or unsubstituted N-heterocycles, substituted or unsubstituted amino groups, and substituted or unsubstituted alkyl groups; R13 is R14 is , or .

[0022] In a ninth aspect, the present invention provides a method for preparing an orexin receptor (OXR) antagonist, comprising the following steps: subjecting an ABCA derivative represented by formula III-1 or III-2 to an R6 group substitution reaction to obtain the antagonist.

[0023] In a tenth aspect, the present invention provides an azatidine biosteroid, the structure of which is shown in formula IV-3 or IV-4: IV-3; IV-4; Where n is a positive integer from 0 to 2; The groups of R7 and R8 are: when R7 is CH, R8 is H, COOMe, or COO. i Any of the following in Pr; when R7 is N, R8 is C. The groups of R7 and R8 are: when R7 is CH, R8 is H, a substituted or unsubstituted ester group, a substituted or unsubstituted carboxyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted hydroxyl group; when R7 is N, R8 is an amino protecting group or a substituted or unsubstituted aryl group. R10 is R14 is ; R11 and R12 are both NO2; R15 is COCH2; R16 is a halogen.

[0024] Eleventhly, the present invention provides a method for preparing azatidine biosteroids, comprising the following steps: R10 is... The ABCA derivative shown in Formula III-2 undergoes a substitution reaction of the R6 group, followed by the substitution of the SEM group with H, to obtain the product; or The ABCA derivative shown in Formula III-3 is obtained by substituting the R6 group.

[0025] Compared with the prior art, the present invention has the following beneficial effects: 1. Using the synthetic route of this invention, a general method for synthesizing different ABCA compounds is invented, which is an unprecedented comprehensive strategy for constructing ABCA compounds by using a strained tricyclic framework (i.e., the tricyclic compound shown in Formula I).

[0026] 2. By utilizing the stereocontrolled transformation of strained CN bonds, this method provides a modular approach to synthesize a variety of nitrogen-containing bicyclic compounds. This study highlights the potential of these compounds in drug discovery, particularly in the development of orexin receptor antagonists and bioisocapable compounds.

[0027] 3. The synthetic route of this invention can be used for the successful synthesis of various ABCA derivatives, such as 3,6-diazabicyclo[3.1.1]heptane, and their application in the preparation of bioisomer analogs with enhanced pharmacological characteristics. This method overcomes the limitations of conventional methods and provides a robust framework for expanding the diversity of the ABCA library. This work highlights the importance of ABCA in medicinal chemistry and opens up new possibilities for designing therapeutic agents with higher selectivity and efficacy. Detailed Implementation

[0028] The present invention will now be described in detail with reference to specific embodiments. These embodiments will help those skilled in the art to further understand the present invention, but do not limit the invention in any way. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention. These all fall within the scope of protection of the present invention.

[0029] Example 1: Preparation of Compound 1 This embodiment provides a method for preparing compound 1, the specific steps of which are as follows: ; 1) At 0 °C, 1,4-dioxane hydrochloride (56.3 mL, 4 M, 225 mmol) was added to 1-Boc-3-hydroxy-1,2,3,6-tetrahydropyridine (15.0 g, 75 mmol) in a 250 mL vial, and the mixture was stirred at 25 °C for 1 hour. The reaction solution was filtered through a Buchner funnel and washed with 1,4-dioxane to give 6.68 g of the compound shown in formula SI-1, in 90% yield.

[0030] The compound shown in formula SI-1: yellow solid, mp 99-100 ℃ 1 H NMR (500 MHz, Methanol- d 4): δ 6.06 (ddt, J = 10.6, 4.5, 2.2 Hz, 1H), 5.90 (dtd, J = 10.5, 3.2, 1.0Hz, 1H), 4.36 (tdt, J = 4.0, 2.7, 1.3 Hz, 1H), 3.67 (dq, J = 4.0, 2.0 Hz, 2H), 3.33 (dd, J = 12.3, 3.5 Hz, 1H), 3.24 (dd, J = 12.7, 4.0 Hz, 1H). 13 C NMR (126 MHz, Methanol-) d 4): δ 128.24, 122.03, 59.06, 47.29, 41.54. HRMS ( m / z ): [M+H] + calcd for C5H 10 NO + 100.0762, found 100.0759. 2) DIPEA (34.8 mL, 200 mmol) was added to a DCM (100 mL) solution of the compound shown in formula SI-1 (5.0 g, 50 mmol), and the reaction vessel was backfilled three times with argon gas. After cooling the mixture to 0 °C, CbzCl (10.5 mL, 75 mmol) was added dropwise using a syringe, and the reaction solution was stirred at 25 °C for 3 hours under an argon atmosphere. A saturated NH4Cl aqueous solution (50 mL) was added to the reaction solution, and the mixture was extracted with DCM (3 × 100 mL). The combined organic layers were washed with brine, dried with Na2SO4, and concentrated under vacuum. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 2:1) to give 8.74 g of the compound shown in formula SI-2, with a yield of 75%.

[0031] The compound shown in formula SI-2: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 7.39 – 7.27 (m,5H), 5.91 (dd, J = 10.3, 3.1 Hz, 1H), 5.81 (d, J = 33.7 Hz, 1H), 5.15 (s,2H), 4.21 (d, J = 27.3 Hz, 1H), 4.02 (d, J = 16.1 Hz, 1H), 3.88 (d, J = 19.4Hz, 1H), 3.76 – 3.44 (m, 2H), 2.53 – 2.05 (m, 1H). 13 C NMR (126 MHz, CDCl3): δ155.83, 136.52, 128.54, 128.11, 127.97, 127.38, 126.45, 67.36, 63.45, 47.96,47.63, 43.36. HRMS ( m / z ): [M+Na] + calcd for C 13 H 15 NNaO3 + 256.0950, found 256.0949. ; 3) To a DCM (100 mL) solution of the compound shown in formula SI-2 (23.3 g, 100 mmol), NaHCO3 (8.4 g, 100 mol) was added, and the reaction vessel was backfilled three times with argon gas. After cooling the mixture to 0 °C, a DCM (300 mL) solution of mCPBA (85%; 30.35 g, 150 mmol) was added dropwise using a syringe, and the reaction solution was stirred at 25 °C for 12 hours under an argon atmosphere. After half of the solvent was evaporated, a saturated Na2SO3 aqueous solution (40 mL) was added to the reaction solution. The mixture was extracted with DCM (3 × 200 mL). The combined organic layers were washed with brine, dried with Na2SO4, and concentrated under vacuum. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 2:1) to give 19.92 g of the compound shown in formula SI-3, in 80% yield.

[0032] The compound shown in formula SI-3: a colorless oily substance. 1 H NMR (400 MHz, CDCl3): δ 7.38 – 7.23 (m,5H), 5.09 (s, 2H), 4.07 – 3.94 (m, 1H), 3.93 – 3.65 (m, 2H), 3.67 – 3.45 (m,2H), 3.43 – 3.31 (m, 2H), 3.07 – 2.92 (m, 1H). 13 C NMR (101 MHz, CDCl3): δ155.45, 136.30, 128.56, 128.20, 127.98, 67.51, 64.94, 54.26, 53.34, 52.90,43.94, 43.52, 41.34. HRMS ( m / z ): [M+Na] + calcd for C 13 H 15 NNaO4 + 272.0899, found 272.0898. 4) Add MgSO4 (9.6 g, 80 mmol) and potassium azide (6.5 g, 80 mmol) to an aqueous (100 mL) solution of the compound shown in formula SI-3 (5.0 g, 20 mmol). Stir the reaction solution at 50 °C for 12 hours. Extract the reaction solution with EA (3 × 100 mL). Wash the combined organic layers with brine, dry with Na2SO4, and concentrate under vacuum. Purify the crude product by silica gel rapid column chromatography (hexane:ethyl acetate, 1:1) to give 3.85 g of the compound shown in formula SI-4-1 (66% yield) and 1.28 g of the compound shown in formula SI-4-2 (22% yield).

[0033] The compound shown in formula SI-4-1 is a white solid with a mp value of 105-106 °C. 1 H NMR (500 MHz, CDCl3): δ7.40 – 7.29 (m, 5H), 5.14 (d, J = 9.6 Hz, 2H), 4.26 – 3.91 (m, 3H), 3.70 (d, J = 11.9 Hz, 1H), 3.57 (s, 1H), 3.46 – 3.33 (m, 1H), 3.21 (s, 1H), 3.10 (dd, J = 14.2, 2.3 Hz, 1H), 2.87 (d, J = 37.7 Hz, 1H). 13 C NMR (126 MHz, CDCl3): δ156.10, 136.14, 128.59, 128.25, 127.92, 77.32, 77.06, 76.81, 73.36, 67.86,67.26, 59.38, 47.26, 45.20. HRMS ( m / z ): [M+Na] + calcd for C 13 H 16 N4NaO4 + 315.1069, found 315.1069. The compound shown in formula SI-4-2 is a white solid with a mp value of 170-172 °C. 1 H NMR (400 MHz, DMSO- d6): δ 7.43 – 7.25 (m, 5H), 5.64 – 5.55 (m, 2H), 5.06 (s, 2H), 4.09 – 3.89 (m, 2H), 3.26 – 3.11 (m, 3H), 2.72 – 2.51 (m, 2H). 13 C NMR (101 MHz, DMSO- d 6): δ 154.70, 137.15, 128.92, 128.41, 128.08, 72.44, 68.30, 67.01, 48.85. HRMS( m / z ): [M+Na] + calcd for C 13 H 16 N4NaO4 + 315.1069, found 315.1067. ; 5) Add Et3N (5.55 mL, 40 mmol) to a DCM (50 mL) solution of the compound shown in formula SI-4-1 or SI-4-2 (2.92 g, 10 mmol), and backfill the reaction vessel three times with argon gas. After cooling the mixture to 0 °C, add a DCM (50 mL) solution of methanesulfonic anhydride (8.7 g, 50 mmol) dropwise using a syringe, and stir the reaction solution at 25 °C for 3 hours under an argon atmosphere. Wash the reaction solution with a saturated NaHCO3 aqueous solution (30 mL) and extract with DCM (3 × 100 mL). Wash the combined organic layers with brine, dry with Na2SO4, and concentrate under vacuum. Purify the crude product by silica gel rapid column chromatography (hexane:ethyl acetate, 2:1) to obtain 3.85 g of the compound shown in formula SI-5-1 (86% yield) and 3.94 g of the compound shown in formula SI-5-2 (88% yield).

[0034] The compound shown in formula SI-5-1: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 7.46 – 7.29(m, 5H), 5.16 (d, J = 2.4 Hz, 2H), 5.03 (d, J = 42.7 Hz, 1H), 4.68 – 4.19 (m,3H), 3.99 – 3.84 (m, 1H), 3.19 (s, 4H), 3.02 (d, J = 35.7 Hz, 4H). 13C NMR (126 MHz, CDCl3): δ 155.29, 135.84, 128.64, 128.41, 128.17, 79.21, 78.27,75.54, 74.53, 68.24, 56.89, 56.34, 46.75, 45.82, 45.58, 45.41, 38.82, 38.63,38.41. HRMS ( m / z ): [M+Na] + calcd for C 15 H 20 N4NaO8S2 + 471.0620, found 471.0620. The compound shown in formula SI-5-2 is a colorless oil. 1 H NMR (500 MHz, CDCl3): δ 7.40 – 7.28 (m, 5H), 5.15 (s, 2H), 4.50 (dd, J = 13.9, 4.9 Hz, 2H), 4.38(s, 2H), 3.71 (t, J = 9.0 Hz, 1H), 3.12 (s, 6H), 3.08 – 2.96 (m, 2H). 13 C NMR (126 MHz, CDCl3): δ 154.42, 135.74, 128.65, 128.41, 128.03, 74.98, 68.17,65.25, 46.27, 38.49. HRMS ( m / z ): [M+Na] + calcd for C 15 H 20 N4NaO8S2 + 471.0620, found 471.0619. 6) Add a 50 mL solution of PPh3 (2.62 g, 10 mmol) in MeCN to the reaction vessel and backfill three times with argon gas. Add a solution of the compound shown in formula SI-5-1 / SI-5-2 (3.13 g, 10 mmol) in 100 mL of MeCN dropwise using a syringe, and stir the reaction solution at 25 °C for 3 hours under an argon atmosphere. Concentrate the reaction solution under vacuum to obtain the crude product of the compound shown in formula SI-6. The crude product is used directly in the next step. Yield: 92% (using dibromomethane as an internal standard, obtained by...). 1(H NMR determination). Note: The mixture was used directly without separation.

[0035] Compound represented by formula SI-6: colorless oily substance, HRMS ( m / z ): [M+H] + calcd for C 33 H 36 N2O8PS2 + 683.1651, found 683.1649. TLC: R f = 0.4 (10:1 dichloromethane:methanol). ; 7) Add 1 M NaOH aqueous solution (20 mL) to a DCM (20 mL) solution of the compound shown in formula SI-6 (6.3 g, 9.2 mmol). Stir the reaction solution at 25 °C for 5 min, and extract the mixture with DCM (3 × 20 mL). Wash the combined organic layers with brine, dry with Na2SO4, and concentrate under vacuum. Purify the crude product by silica gel rapid column chromatography (dichloromethane:diethyl ether, 1:1) to give 2.55 g of the compound shown in formula SI-7, in 82% yield.

[0036] The compound represented by formula SI-7: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 7.40 – 7.28 (m,5H), 5.30 – 4.95 (m, 3H), 4.17 – 3.85 (m, 2H), 3.56 (t, J = 15.0 Hz, 1H), 3.33 (dd, J = 27.4, 14.5 Hz, 1H), 3.07 (s, 1.5H), 2.85 (s, 1.5H), 2.70 – 2.49 (m, 2H). 13 C NMR (126 MHz, CDCl3): δ 155.78, 155.35, 136.47, 128.57, 128.15, 127.93, 74.89, 73.95, 67.46, 67.37, 42.25, 42.06, 41.93, 41.49, 38.97, 38.45, 30.62, 30.42, 28.28, 27.87. Note: Two isomers in a 2:3 ratio were observed, attributed to rotational isomerization of the amide. HRMS ( m / z ): [M+H] + calcd for C 14 H 19N2O5S + 327.1015, found 327.1014. 8) A DCM (10 mL) solution of the compound of formula SI-7 (326 mg, 1 mmol) was added to the reaction vessel, and backfilled three times with argon. After cooling the mixture to -78 °C, t-BuOK (1.0 mol / L, THF, 1.5 mL, 1.5 mmol) was added dropwise by syringe, and the reaction solution was stirred at 0 °C for 3 hours under an argon atmosphere. The reaction solution was concentrated under vacuum, dissolved in MeCN, and filtered through diatomaceous earth to obtain the crude product of the compound of formula 1. The crude product was used directly for further reactions. Yield: 78% (using dibromomethane as an internal standard, obtained by filtration of the crude reaction mixture). 1 H NMR determination).

[0037] The compound shown in Formula 1: 1 H NMR (400 MHz, CDCl3): δ 7.40 – 7.26 (m, 5H), 5.13 (d, J = 2.4 Hz, 2H), 3.70 (dq, J = 13.9, 2.5 Hz, 2H), 3.26 – 3.12 (m, 4H), 2.73(p, J = 2.0 Hz, 1H). 13 C NMR (101 MHz, CDCl3): δ 155.16, 136.50, 128.53, 128.13, 127.99, 67.12, 58.15, 57.79, 36.72, 36.34, 25.87. Example 2: Preparation of Compound 2 and SI-93 This embodiment provides a method for preparing compound 2 and SI-93, the specific steps of which are as follows: ; 1) The preparation steps are the same as step 3 in Example 1, except that: NaHCO3 (16.8 g, 200 mol) was added to a DCM (200 mL) solution of cyclohexyl-2-en-1-ol (compound 5, 19.6 g, 200 mmol), and the reaction vessel was backfilled three times with argon gas. After cooling the mixture to 0 °C, a DCM (400 mL) solution of mCPBA (85%; 60.7 g, 300 mmol) was added dropwise using a syringe. The reaction solution was stirred at 0 °C for 3 hours under an argon atmosphere, and then heated to room temperature. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 3:1) to obtain 18.47 g of the compound shown in formula SI-8, with a yield of 81%.

[0038] The compound represented by formula SI-8: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 3.86 (ddd, J =8.2, 5.2, 2.5 Hz, 1H), 3.31 (s, br., 1H), 3.18 (ddd, J = 6.6, 4.5, 2.7 Hz,2H), 1.71 – 1.62 (m, 2H), 1.50 – 1.37 (m, 2H), 1.36 – 1.26 (m, 1H), 1.19 –1.04 (m, 1H). 13 C NMR (126 MHz, CDCl3): δ67.32, 55.59, 55.23, 28.29, 22.82,18.85. HRMS ( m / z ): [M+Na] + calcd for C6H 10 NaO2 + 137.0578, found 137.0579. 2) The preparation steps are the same as step 4 in Example 1, except that MgSO4 (30.0 g, 250 mmol) and potassium azide (20.3 g, 250 mmol) were added to an aqueous (200 mL) solution of the compound of formula SI-8 (11.4 g, 100 mmol). The crude product was purified by crystallization (ether / methanol) to obtain 13.03 g of the compound of formula SI-9, with a yield of 83%.

[0039] The compound shown in formula SI-9 is a white solid with a mp value of 70-71 °C. 1 H NMR (400 MHz, CDCl3): δ4.01 (q,J = 3.4 Hz, 1H), 3.84 (s, br., 1H), 3.59 (td, J = 10.1, 4.3 Hz, 1H), 3.47 (s, br., 1H), 3.38 (dd, J = 9.4, 2.9 Hz, 1H), 1.96 (dq, J = 13.3, 5.1,4.5 Hz, 1H), 1.83 (dd, J = 14.2, 4.4 Hz, 1H), 1.65 (qt, J = 12.6, 3.7 Hz, 1H), 1.50 (dt, J = 13.7, 4.0 Hz, 1H), 1.40 (tt, J = 13.4, 3.6 Hz, 1H), 1.28(qd, J = 12.3, 3.9 Hz, 1H). 13 C NMR (126 MHz, CDCl3): δ 74.75, 69.54, 61.92,30.11, 29.17, 18.20. HRMS ( m / z ): [M-N2+H] + calcd for C6H 12 NO2 + 130.0868, found 130.0866. 3) The preparation steps are the same as step 5 in Example 1, except that: Et3N (27.7 mL, 200 mmol) was added to a DCM (200 mL) solution of the compound shown in formula SI-9 (7.85 g, 50 mmol), and the reaction vessel was backfilled three times with argon gas. After cooling the mixture to 0 °C, a DCM (200 mL) solution of methanesulfonic anhydride (43.5 g, 250 mmol) was added dropwise using a syringe. The crude product was purified by crystallization (ether / methanol) to obtain 12.52 g of the compound shown in formula SI-92, with a yield of 80%.

[0040] The compound shown in formula SI-92 is a white solid with a mp value of 83-85 °C. 1 H NMR (400 MHz, CDCl3): δ5.08 (dt, J = 4.9, 2.6 Hz, 1H), 4.41 (dd, J= 9.7, 3.0 Hz, 1H), 3.87 (td, J =10.0, 5.0 Hz, 1H), 3.18 (s, 3H), 3.12 (s, 3H), 2.24 – 2.13 (m, 2H), 1.86 –1.58 (m, 3H), 1.49 – 1.39 (m, 1H). 13 C NMR (101 MHz, CDCl3): δ 81.00, 79.36,59.00, 38.53, 38.41, 29.66, 29.46, 17.54. HRMS ( m / z ): [M+Na] + calcd forC8H 15 N3NaO6S2 + 336.0300, found 336.0297. ; 4) Add 30% Pd / C (940 mg) to a solution of the compound (3.13 g, 10 mmol) in MeOH (50 mL) and THF (25 mL), and backfill the reaction vessel three times with hydrogen. Stir the reaction solution at 25 °C under a hydrogen atmosphere for 12 hours. Filter the reaction solution through diatomaceous earth and concentrate it under vacuum. Purify the crude product by silica gel rapid column chromatography (dichloromethane:methanol, 20:1) to obtain 2.44 g of the compound (SI-10), with a yield of 85%.

[0041] The compound shown in formula SI-10 is a white solid with a mp of 112-114 °C. 1 H NMR (500 MHz, CDCl3): δ5.14 (dd, J = 4.7, 2.5 Hz, 1H), 4.30 (dd, J = 9.6, 2.9 Hz, 1H), 3.22-3.16 (m,4H), 3.09 (s, 3H), 2.20 – 2.12 (m, 1H), 2.04 – 1.97 (m, 1H), 1.76 – 1.59 (m,3H), 1.40 (s, 2H), 1.31 – 1.19 (m, 1H). 13 C NMR (126 MHz, CDCl3): δ 84.99,79.30, 48.82, 38.66, 38.52, 32.94, 30.21, 18.29. HRMS ( m / z ): [M+H] + calcd forC8H 18 NO6S2 + 288.0576, found 288.0575. 5) The preparation steps are the same as step 6 in Example 1, except that: the compound of formula SI-92 (3.13 g, 10 mmol) in a solution of MeCN (100 mL) was added dropwise using a syringe. The crude product of the compound of formula SI-11 was obtained. Yield: 83%.

[0042] The compound represented by formula SI-11: a colorless oily substance. 1 H NMR (400 MHz, CDCl3): δ 7.87 – 7.61(m, 15H), 5.26 – 5.17 (m, 1H), 3.12 (s, 3H), 2.88 – 2.82 (m, 1H), 2.82 – 2.78(m, 1H), 2.60 (s, 3H), 2.19 (tt, J = 15.2, 4.8 Hz, 2H), 1.94 (tt, J = 10.9,4.4 Hz, 1H), 1.66 (hept, J = 4.4 Hz, 2H), 1.53 – 1.39 (m, 1H). 13 C NMR (101MHz, CDCl3): δ 136.05, 136.02, 133.54, 133.44, 130.70, 130.57, 118.42,117.43, 74.13, 74.08, 41.34, 41.26, 39.98, 39.90, 39.43, 38.14, 27.06, 22.95,14.57. 31 P NMR (162 MHz, CDCl3): δ 49.08. HRMS ( m / z ): [M+H] + calcd forC 26 H 31 NO6PS2 + 548.1330, found 548.1331. 6) The preparation steps are the same as step 8 in Example 1, except that: a 100 mL THF solution of the compound shown in formula SI-10 (2.87 g, 10 mmol) was used, and 0.2 mol / L PhLi diethyl ether solution (100 mL, 20 mmol) was added dropwise using a syringe. The crude product of the compound shown in formula 2 was obtained. Yield: 69%. Note: Preparation of 0.2 mol / L PhLi diethyl ether solution: A 250 mL dry vial was prepared, backfilled three times with argon gas, and anhydrous diethyl ether (80 mL) was added dropwise using a syringe. After cooling to 0 °C, 1 mol / L PhLi (20 mL, 20 mmol) was added dropwise using a syringe.

[0043] The compound shown in Formula 2: 1 H NMR (400 MHz, CDCl3): δ 3.12 (dt, J = 3.0, 1.4 Hz, 2H), 2.57 (p, J = 1.9 Hz, 1H), 1.60 – 1.49 (m, 4H), 1.41 – 1.37 (m, 1H), 1.35– 1.28 (m, 1H). 7) The preparation steps are the same as step 8 in Example 1, except that a 10 mL solution of DCM containing 547 mg (1 mmol) of the compound of formula SI-11 was added to the reaction vessel. The crude product of the compound of formula SI-93 was obtained. Yield: 70%.

[0044] Compounds represented by formula SI-93: 1 H NMR (400 MHz, CDCl3): δ 7.71 – 7.49 (m, 15H), 4.84 (p, J = 2.8 Hz, 1H), 3.44 (d, J = 13.4 Hz, 1H), 3.33 (dd, J = 13.4, 7.1Hz, 1H), 3.06 (dddd, J = 19.8, 10.4, 8.7, 4.1 Hz, 1H), 2.57 (ddd, J = 10.4,6.8, 3.6 Hz, 1H), 2.10 (dt, J = 14.9, 2.4 Hz, 1H), 1.73 (qd, J = 5.1, 1.9 Hz,1H), 1.65 – 1.35 (m, 4H). Example 3: Preparation of Compound 3 and SI-17 This embodiment provides a method for preparing compounds 3 and SI-17, the specific steps of which are as follows: ; 1) Cerium trichloride heptahydrate (30.8 g, 125 mmol) was added to a methanol (300 mL) solution of 2-cyclopenten-1-one (compound 11, 10.25 g, 125 mmol) and stirred until dissolved. After cooling the mixture to 0 °C, NaBH4 (9.5 g, 250 mmol) was slowly added over 30 minutes, and the reaction solution was stirred at 25 °C for 30 minutes. A saturated NaCl aqueous solution (100 mL) was added to the reaction solution, and the mixture was concentrated under vacuum (35 °C, 80 mbar). Then, it was extracted with diethyl ether (3 × 300 mL). The combined organic layers were dried over Na2SO4 and concentrated under vacuum (35 °C, 80 mbar) to give 8.40 g of the compound shown in formula SI-12, in 80% yield.

[0045] The compound represented by formula SI-12: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 5.86 (dtd, J =5.7, 2.3, 1.1 Hz, 1H), 5.72 (dq, J = 6.1, 2.1 Hz, 1H), 4.74 (ddp, J = 7.3,3.6, 1.1 Hz, 1H), 3.28 (s, 1H), 2.40 (tddd, J = 11.0, 6.6, 4.8, 2.8 Hz, 1H), 2.24 – 2.05 (m, 2H), 1.65 – 1.52 (m, 1H). 13 C NMR (126 MHz, CDCl3): δ 134.58,133.31, 77.08, 32.95, 30.92. HRMS ( m / z ): [MH] - calcd for C5H7O - 83.0497, found 83.0498. 2) The preparation steps are the same as step 3 in Example 1, except that: the compound shown in formula SI-12 (8.4 g, 100 mmol) was used, and the reaction solution was stirred at 0 °C for 3 hours under an argon atmosphere and then heated to room temperature. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 1:1) to obtain 6.30 g of the compound shown in formula SI-13, with a yield of 63%.

[0046] The compound shown in formula SI-13: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 4.24 (td, J =8.1, 1.5 Hz, 1H), 3.50 – 3.38 (m, 2H), 2.70 (s, br., 1H), 2.06 (dd, J = 14.4, 8.4 Hz, 1H), 1.90 (dt, J = 13.0, 8.2 Hz, 1H), 1.62 (dddd, J = 14.3, 10.1,8.5, 1.3 Hz, 1H), 1.23 (ddd, J = 10.3, 4.4, 2.2 Hz, 1H). 13 C NMR (126 MHz, CDCl3): δ73.50, 58.92, 56.22, 26.84, 25.91. HRMS ( m / z ): [MH] - calcd for C5H7O2 - 99.0446, found 99.0445. 3) The preparation steps are the same as step 4 in Example 1, except that MgSO4 (18.0 g, 150 mmol) and potassium azide (12.2 g, 15 mmol) were added to an aqueous (100 mL) solution of the compound of formula SI-13 (5.0 g, 50 mmol). This yielded 4.43 g of the compound of formula SI-14, with a yield of 62%.

[0047] The compound represented by formula SI-14: a colorless oily substance. 1 H NMR (400 MHz, CDCl3): δ 4.10 (dt, J=7.8, 3.9 Hz, 1H), 3.95 (s, br., 1H), 3.87 – 3.75 (m, 2H), 3.54 (s, br., 1H), 2.23 – 2.09 (m, 1H), 2.03 (ddt, J = 15.5, 10.9, 5.7 Hz, 1H), 1.74 – 1.61 (m,1H), 1.50 (ddt, J = 13.6, 9.9, 6.7 Hz, 1H). 13 C NMR (101 MHz, CDCl3): δ 78.30,71.47, 65.64, 28.96, 25.71. HRMS ( m / z ): [M-N2+H] + calcd for C5H 10 NO2 + 116.0712, found 116.0711. 4) The preparation steps are the same as step 5 in Example 1, except that: Et3N (16.6 mL, 120 mmol) was added to a DCM (100 mL) solution of the compound shown in formula SI-14 (4.3 g, 30 mmol); a DCM (100 mL) solution of methanesulfonic anhydride (26.1 g, 150 mmol) was added dropwise using a syringe. The crude product was purified by crystallization (ether / methanol) to obtain 5.38 g of the compound shown in formula SI-15, with a yield of 60%.

[0048] The compound shown in formula SI-15 is a white solid with a mp value of 51-53 °C. 1 H NMR (500 MHz, CDCl3): δ5.08 (td, J = 5.3, 2.8 Hz, 1H), 4.67 (dd, J = 7.8, 4.4 Hz, 1H), 4.20 (dt, J =9.1, 7.3 Hz, 1H), 3.15 (s, 3H), 3.08 (s, 3H), 2.42 – 2.31 (m, 1H), 2.24 (ddt, J = 16.3, 11.3, 5.8 Hz, 1H), 2.11 (dddd, J = 15.3, 10.0, 5.4, 2.7 Hz, 1H),1.67 (dddd, J= 13.9, 10.5, 6.9, 5.4 Hz, 1H). 13 C NMR (126 MHz, CDCl3): δ82.57, 79.45, 62.37, 38.52, 38.51, 27.59, 24.76. HRMS ( m / z ): [M+Na] + calcdfor C7H 13 N3NaO6S2 + 322.0143, found 322.0142. ; 5) The preparation steps are the same as step 4 in Example 2, except that 30% Pd / C (180 mg) was added to a solution of the compound shown in formula SI-15 (600 mg, 2 mmol) in MeOH (10 mL) and THF (5 mL). The crude product was purified by silica gel rapid column chromatography (dichloromethane:methanol, 10:1) to obtain 453.2 mg of the compound shown in formula SI-16, with a yield of 83%.

[0049] The compound shown in formula SI-16 is a white solid with a mp value of 108-110 °C. 1 H NMR (500 MHz, DMSO- d 6):δ 5.09 (dt, J = 6.1, 4.2 Hz, 1H), 4.59 (dd, J = 6.8, 4.4 Hz, 1H), 3.34 – 3.29(m, 1H), 3.27 (s, 3H), 3.18 (s, 3H), 2.21 – 2.12 (m, 1H), 2.06 (dddd, J =13.5, 10.1, 8.5, 5.1 Hz, 1H), 1.81 (dddd, J = 14.1, 10.1, 6.3, 4.0 Hz, 1H),1.30 (ddt, J = 13.3, 10.3, 6.6 Hz, 1H). 13 C NMR (126 MHz, DMSO- d 6): δ 90.57,85.15, 59.23, 43.05, 42.97, 32.79, 32.09. HRMS ( m / z ): [M+H] +calcd forC7H 16 NO6S2 + 274.0419, found 274.0419. 6) The preparation steps are the same as step 6 in Example 2, except that the compound shown in formula SI-16 (273 mg, 1 mmol) was used. The crude product of the compound shown in formula 3 was obtained. Yield: 65%.

[0050] The compound shown in Formula 3: 1 H NMR (500 MHz, CDCl3): δ 2.77 (s, 1H), 2.45 (s, 1H), 1.50 – 1.45 (m, 1H), 1.39 – 1.33 (m, 1H). 7) The preparation steps are the same as step 6 in Example 1, except that: a solution of the compound shown in formula SI-15 (300 mg, 1 mmol) in MeCN (10 mL) was added dropwise using a syringe. The crude product of the compound shown in formula SI-17 was obtained. Yield: 78%. Note: Compound 3 was prepared using the same method as step 8) in Example 1, but compound 3 was not obtained.

[0051] The compound represented by formula SI-17: a colorless oily substance. 1 H NMR (400 MHz, CDCl3): δ 7.87 – 7.65(m, 15H), 5.56 (d, J = 4.3 Hz, 1H), 3.40 (dd, J = 15.2, 4.1 Hz, 1H), 3.23(ddd, J = 13.5, 4.0, 1.8 Hz, 1H), 3.17 (s, 3H), 2.56 (s, 3H), 2.33 – 2.19 (m, 2H), 2.17 – 2.04 (m, 2H). 13 C NMR (101 MHz, CDCl3): δ 136.09, 136.06, 133.31,133.20, 130.81, 130.68, 118.80, 117.81, 80.57, 80.50, 53.57, 45.58, 39.43,38.42, 28.25, 25.49. 31 P NMR (162 MHz, CDCl3): δ 46.05. HRMS ( m / z ): [M+H] +calcd for C 25 H 29 NO6PS2 + 534.1174, found 534.1173. Example 4: Preparation of Compound 4 and SI-23 This embodiment provides a method for preparing compounds 4 and SI-23, the specific steps of which are as follows: ; 1) The preparation steps are the same as step 1) in Example 3, except that 2-cyclohepten-1-one (compound 13, 11.0 g, 100 mmol), cerium trichloride heptahydrate (24.6 g, 100 mmol), and NaBH4 (7.6 g, 200 mmol) were added. 9.52 g of the compound shown in formula SI-18 was obtained, with a yield of 85%.

[0052] The compound represented by formula SI-18: a colorless oily substance. 1 H NMR (400 MHz, CDCl3): δ 5.70 – 5.61(m, 2H), 4.36 – 4.25 (m, 1H), 3.01 (s, br., 1H), 2.16 – 2.04 (m, 1H), 2.00 –1.90 (m, 1H), 1.88 – 1.74 (m, 2H), 1.62 – 1.48 (m, 3H), 1.33 – 1.22 (m, 1H). 13 C NMR (101 MHz, CDCl3): δ 138.20, 129.66, 71.91, 36.59, 28.60, 26.96, 26.69.HRMS ( m / z ): [MH] - calcd for C7H 11 O - 111.0810, found 111.0809. 2) The preparation steps are the same as step 3 in Example 1, except that a DCM (200 mL) solution of the compound of formula SI-18 (9.5 g, 85 mmol), NaHCO3 (7.14 g, 85 mol), and mCPBA (85%; 25.8 g, 128 mmol) was used. The reaction solution was stirred at 0 °C for 3 hours under an argon atmosphere. 9.25 g of the compound of formula SI-19 was obtained, with a yield of 85%.

[0053] The compound represented by formula SI-19: a colorless oily substance.1 H NMR (400 MHz, CDCl3): δ 4.01 (ddd, J =10.7, 3.6, 1.1 Hz, 1H), 3.90 – 3.77 (m, 0.5H), 3.27 – 3.22 (m, 1H), 3.14 (td, J = 5.3, 4.8, 1.5 Hz, 1H), 3.10 – 3.01 (m, 1H), 2.66 (s, br., 1.5H), 2.29 –2.14 (m, 1.5H), 1.84 – 1.29 (m, 10.5H), 0.94 (dtt, J = 14.8, 12.5, 2.7 Hz, 1H). Note: dr = 2:1 HRMS ( m / z ): [M+Na] + calcd for C7H 12 NaO2 + 151.0735, found151.0735. 3) The preparation steps are the same as step 4 in Example 1, except that the compound shown in formula SI-19 (3.84 g, 30 mmol), MgSO4 (10.8 g, 90 mmol), and potassium azide (7.29 g, 90 mmol) were used. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 2:1) to obtain 4.10 g of the compound shown in formula SI-20, with a yield of 80%.

[0054] Compound represented by formula SI-20: colorless oil, HRMS ( m / z ): [M-N2+H] + calcd for C7H 14 NO2 + 144.1025, found 144.1026. 4) The preparation steps are the same as step 5 in Example 1, except that the following were used: compound SI-20 (4.1 g, 24 mmol), Et3N (13.3 mL, 96 mmol), and methanesulfonic anhydride (20.9 g, 120 mmol). The crude product was purified by crystallization (ether / methanol) to obtain 5.49 g of compound SI-21, with a yield of 70%.

[0055] The compound shown in formula SI-21 is a white solid with a mp value of 122-123 °C. 1H NMR (400 MHz, CDCl3): δ5.13 (dt, J = 8.1, 1.9 Hz, 1H), 4.59 (dd, J = 8.0, 1.7 Hz, 1H), 3.90 (ddd, J = 8.1, 6.7, 4.5 Hz, 1H), 3.17 (s, 3H), 3.12 (s, 3H), 2.34 – 2.18 (m, 1H), 2.11 – 2.00 (m, 1H), 1.91 – 1.62 (m, 6H). 13 C NMR (126 MHz, CDCl3): δ 85.11,81.54, 62.64, 38.68, 38.23, 29.31, 28.63, 22.11, 21.45. HRMS ( m / z ): [M+Na] + calcd for C9H 17 N3NaO6S2 + 350.0456, found 350.0455. ; 5) The preparation steps are the same as step 4 in Example 2, except that 20% Pd / C (100 mg) was added to a solution of the compound of formula SI-21 (500 mg, 1.5 mmol) in MeOH (10 mL) and THF (5 mL). 361.2 mg of the compound of formula SI-22 was obtained, with a yield of 80%.

[0056] The compound represented by formula SI-22: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 5.19 (dd, J =8.5, 2.0 Hz, 1H), 4.55 (dd, J = 7.4, 1.8 Hz, 1H), 3.27 (td, J = 7.7, 4.4 Hz,1H), 3.16 (s, 3H), 3.09 (s, 3H), 2.19 (ddt, J = 13.9, 10.2, 5.4 Hz, 1H), 1.92(ddd, J = 13.3, 7.3, 3.9 Hz, 1H), 1.88 – 1.79 (m, 1H), 1.75 (ddt,J = 12.8,9.5, 4.3 Hz, 2H), 1.72 – 1.56 (m, 4H), 1.48 (dt, J = 15.8, 8.2 Hz, 1H). 13 CNMR (126 MHz, CDCl3): δ 88.43, 80.98, 52.10, 38.75, 38.47, 32.80, 28.58,22.43, 21.94. HRMS ( m / z ): [M+H] + calcd for C9H 20 NO6S2 + 302.0732, found 302.0734. 6) The preparation steps are the same as step 6 in Example 2, except that a 2.0 mL solution of THF (60.2 mg, 0.2 mmol) of the compound shown in formula SI-22 and a 2.0 mL solution of 0.2 mol / L PhLi diethyl ether (0.4 mmol) were used. The crude product of the compound shown in formula 4 was obtained. Yield: 25%.

[0057] 7) The preparation steps are the same as step 6 in Example 1, except that the compound shown in formula SI-21 (3.27 g, 10 mmol) was used. The crude product of the compound shown in formula SI-23 was obtained. Yield: 80%.

[0058] The compound represented by formula SI-23: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 7.82 – 7.58(m, 15H), 5.02 (t, J = 7.7 Hz, 1H), 3.22 (s, 1H), 2.98 (s, 3H), 2.79 – 2.60 (m, 2H), 2.50 (s, 3H), 2.40 – 2.30 (m, 1H), 2.04 – 1.90 (m, 2H), 1.74 – 1.57(m, 2H), 1.52 – 1.30(m, 2H). 13C NMR (126 MHz, CDCl3): δ 134.18, 134.16,131.62, 131.54, 128.83, 128.72, 116.62, 115.83, 79.01, 78.98, 48.18, 43.90,43.84, 39.66, 39.60, 37.52, 37.23, 31.08, 27.14, 27.12, 23.44, 21.90. 31 P NMR (202 MHz, CDCl3): δ 46.90. HRMS ( m / z ): [M+H] + calcd for C 27 H 33 NO6PS2 + 562.1487, found 562.1482. Example 5 Preparation of Compound 10 and SI-25 This embodiment provides a method for preparing compounds 10 and SI-25, the specific steps of which are as follows: ; 1) The preparation steps are the same as step 3 in Example 1, except that the compound shown in Formula 6 (19.9 g, 100 mmol) was used. 18.49 g of the compound shown in Formula 7 was obtained, with a yield of 86%.

[0059] The compound shown in Formula 7 is a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 3.98 (s, 1H), 3.90– 3.56 (m, 2H), 3.52 (d, J = 15.3 Hz, 1H), 3.40 (q, J = 3.1 Hz, 2H), δ 2.93(dd, J = 13.1, 8.5 Hz, 1H)., 1.40 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ 154.70,80.44, 65.05, 54.20, 53.71, 53.12, 44.32, 43.14, 41.58, 40.75, 28.32. HRMS( m / z ): [M+Na] + calcd for C 10 H 17 NNaO4 +238.1055, found 238.1055. 2) The preparation steps were the same as step 4 in Example 1, except that the compound shown in Formula 7 (10.75 g, 50 mmol), MgSO4 (15.0 g, 125 mmol), and potassium azide (10.2 g, 125 mmol) were used; the reaction solution was stirred at 50 °C for 18 hours. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 2:1) to obtain 11.22 g of the compound shown in Formula SI-24, with a yield of 87%.

[0060] The compound represented by formula SI-24: a colorless oily substance. 1 H NMR (400 MHz, CDCl3): δ 4.15 – 3.78 (m, 3H), 3.75 – 3.40 (m, 4H), 3.27 – 2.37 (m, 2H), 1.45 (s, 9H). 13 C NMR (101MHz, CDCl3): δ 155.50, 80.91, 73.03, 67.05, 59.48, 46.34, 44.85, 28.30. HRMS( m / z ): [M+Na] + calcd for C 10 H 18 N4NaO4 + 281.1226, found 281.1226. ; 3) The preparation steps are the same as step 5 in Example 1, except that a DCM (100 mL) solution of the compound of formula SI-24 (7.74 g, 30 mmol), a DCM (100 mL) solution of Et3N (16.6 mL, 120 mmol), and a DCM (100 mL) solution of methanesulfonic anhydride (26.1 g, 150 mmol) were used. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 3:1) to obtain 10.68 g of the compound of formula 8, with a yield of 86%.

[0061] The compound shown in Formula 8 is a colorless oily substance. 1 H NMR (400 MHz, CDCl3): δ 5.10 – 4.87 (m,1H), 4.75 – 4.36 (m, 2.4H), 4.28 – 4.01 (m, 0.6H), 3.91 (td, J= 9.9, 5.0 Hz,1H), 3.37 – 3.22 (m, 0.4H), 3.21 (s, 3H), 3.18 – 3.15 (m, 0.4H), 3.14 (s,3H), 3.12 – 3.04 (m, 0.6H), 2.74 – 2.57 (m, 0.6H), 1.49 (s, 9H). 13 C NMR (101MHz, CDCl3): δ 154.30, 81.68, 79.82, 78.28, 76.31, 74.57, 57.04, 56.32, 47.00, 45.20, 44.59, 38.75, 38.51, 38.36, 28.04. Note: Two isomers in a 2:3 ratio were observed, attributed to rotational isomerization of the amide. HRMS ( m / z ): [M+Na] + calcd for C 12 H 22 N4NaO8S2 + 437.0777, found 437.0776. 4) The preparation steps are the same as step 6 in Example 1, except that the compound shown in Formula 8 (3.13 g, 10 mmol) was used. The crude product of the compound shown in Formula 9 was obtained. Yield: 83%.

[0062] The compound shown in Formula 9 is a colorless oily substance. 1 H NMR (400 MHz, CDCl3): δ 7.83 – 7.59 (m,15H), 5.07 (dt, J = 26.4, 7.2 Hz, 1H), 4.28 (dd, J = 22.8, 15.3 Hz, 1H), 4.06(dd, J = 13.8, 5.7 Hz, 0.5H), 3.94 (dd, J = 14.3, 5.2 Hz, 0.5H), 3.80 (d, J =15.7 Hz, 0.5H), 3.72 (d, J = 15.4 Hz, 0.5H), 3.56 (dd, J = 15.2, 6.0 Hz,0.5H), 3.31 (dd, J= 14.0, 8.2 Hz, 0.5H), 3.23 – 3.08 (m, 2.5H), 3.08 – 2.92(m, 2.5H), 2.54 (s, 3H), 1.35 (s, 4.5H), 1.28 (s, 4.5H). 13 C NMR (126 MHz, CDCl3): δ 154.50, 135.29, 135.27, 133.76, 133.67, 132.07, 131.99, 130.16, 130.06, 128.55, 128.45, 121.38, 120.56, 80.98, 69.46, 53.96, 49.96, 46.84, 46.76, 39.49, 38.19, 37.81, 29.27, 27.90. Note: Two 1:1 isomers were observed, attributed to rotational isomerization of the amide. 31 P NMR (202 MHz, CDCl3): δ 39.89. HRMS ( m / z ): [M+H] + calcdfor C 30 H 38 N2O8PS2 + 649.1807, found 649.1805. ; 5) The preparation steps are the same as step 7 in Example 1, except that the compound shown in Formula 9 (5.4 g, 8.3 mmol) was used. The crude product was purified by silica gel rapid column chromatography (dichloromethane:diethyl ether, 5:1) to obtain 1.94 g of the compound shown in Formula SI-25, with a yield of 80%.

[0063] The compound represented by formula SI-25: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 5.03 (d, J =38.2 Hz, 1H), 4.07 – 3.75 (m, 2H), 3.48 (d, J = 14.2 Hz, 1H), 3.34 – 3.15 (m,1H), 3.09 (s, 3H), 2.56 (dd, J = 43.8, 23.9 Hz, 2H), 1.44 (s, 9H). 13C NMR (126 MHz, CDCl3): δ 155.06, 154.75, 80.28, 75.24, 74.36, 62.71, 42.60, 42.13,41.36, 40.71, 38.97, 38.67, 30.69, 28.35. HRMS ( m / z ): [M+H] + calcd forC 11 H 21 N2O5S + 293.1171, found 293.1173. ; 6) The preparation steps are the same as step 8 in Example 1, except that the compound shown in Formula 9 (648 mg, 1 mmol) was concentrated under vacuum and then purified by sublimation (60 °C, 5 × 10⁻² Pa). The compound shown in Formula 10 was obtained, with a yield of 71% and a production rate of 83%.

[0064] The compound shown in Formula 10 is a white solid with a mp of 10⁴–10⁶ °C. 1 H NMR (500 MHz, CDCl3): δ3.62 (dd, J = 20.9, 13.7 Hz, 2H), 3.26 – 3.05 (m, 4H), 2.72 (p, J = 2.0 Hz, 1H), 1.45 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ 154.60, 79.93, 58.24, 57.90,36.97, 35.87, 28.39, 25.86. HRMS ( m / z ): [M+H] + calcd for C 10 H 17 N2O2 + 197.1290, found 197.1295. Example 6 Preparation of compound SI-94 This embodiment provides a method for preparing compound SI-94, the specific steps of which are as follows: ; 1) A suspension of naphthenic acid (compound 14, 6.3 g, 50 mmol) in water (140 mL) was cooled to 0 °C, and then NaHCO3 (12.6 g, 150 mmol) was slowly added. The mixture was then backfilled three times with argon. At 0 °C, an aqueous solution of KI (49.8 g, 300 mmol) and I2 (12.7 g, 50 mmol) (120 mL) was added dropwise by syringe, and the mixture was stirred at 25 °C for 24 hours under an argon atmosphere. The reaction solution was washed with a saturated aqueous solution of NaS2O3 (20 mL) and extracted with DCM (3 × 100 mL). The combined organic layers were dried with Na2SO4, protected from light, concentrated under vacuum, and rapidly concentrated under high vacuum to give 11.34 g of the compound shown in formula SI-26, in 90% yield.

[0065] The compound shown in formula SI-26 is a white solid with a mp value of 132-133 °C. 1 H NMR (500 MHz, CDCl3): δ4.81 (dd, J = 5.9, 4.1 Hz, 1H), 4.59 – 4.39 (m, 1H), 2.78 (d, J = 12.3 Hz, 1H), 2.66 (td, J = 5.2, 3.0 Hz, 1H), 2.48 – 2.34 (m, 2H), 2.11 (dd, J = 16.4,5.3 Hz, 1H), 1.89 (tdd, J = 12.9, 5.3, 2.1 Hz, 1H), 1.81 (dtd, J = 11.4, 5.4, 3.4 Hz, 1H). 13 C NMR (126 MHz, CDCl3): δ 177.79, 80.24, 38.62, 34.52, 29.73,23.78, 23.13. HRMS ( m / z ): [M+H] + calcd for C7H 10 IO2 + 252.9725, found 252.9723. 2) DBU (10 mL, 67.2 mmol) was added to a THF (100 mL) solution of the compound of formula SI-26 (11.3 g, 44.8 mmol), and the mixture was refluxed under an argon atmosphere for 20 hours. The reaction mixture was cooled to room temperature and transferred to a separatory funnel with Et2O (200 mL). HCl (100 mL, 0.5 M) and brine (100 mL) were added. The aqueous layer was extracted with Et2O (3 × 200 mL). The combined organic layers were dried over Na2SO4 and concentrated under vacuum. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate 3:1) to give 5.0 g of the compound of formula SI-27, in 90% yield.

[0066] The compound represented by formula SI-27: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 6.17 (ddd, J =9.9, 5.4, 2.5 Hz, 1H), 5.79 (dt, J = 8.6, 3.4 Hz, 1H), 4.70 (t, J = 5.4 Hz, 1H), 2.85 (t, J = 5.3 Hz, 1H), 2.51 – 2.31 (m, 3H), 2.04 (d, J = 11.2 Hz, 1H). 13 C NMR (126 MHz, CDCl3): δ 179.43, 130.27, 129.31, 73.31, 38.02, 34.41,29.11. HRMS ( m / z ): [M+H] + calcd for C7H9O2 + 125.0603, found 125.0600. 3) The compound shown in formula SI-27 (5.0 g, 40.3 mmol) was added to a suspension of NaHCO3 (3.4 g, 40.3 mmol) in MeOH (100 mL). The mixture was then backfilled three times with argon and stirred at 25 °C for 12 hours under an argon atmosphere. The solvent was evaporated and DCM (60 mL) was added. The mixture was washed with water (100 mL) and brine (100 mL). The aqueous layer was extracted with DCM (2 × 100 mL). The combined organic layers were dried over Na2SO4 and concentrated under vacuum. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate 2:1) to give 6.04 g of the compound shown in formula SI-28, in 96% yield.

[0067] The compound represented by formula SI-28: a colorless oily substance. 1 H NMR (400 MHz, CDCl3): δ 5.76 – 5.67(m, 2H), 4.27 (tdd, J = 8.2, 3.5, 1.6 Hz, 1H), 3.67 (s, 3H), 2.75 – 2.63 (m,1H), 2.31 – 2.22 (m, 3H), 1.70 (ddd, J = 12.8, 10.8, 8.1 Hz, 1H). HRMS ( m / z ):[M+Na] + calcd for C8H 12 NaO3 + 179.0684, found 179.0683. ; 4) The preparation steps are the same as step 3 in Example 1, except that a DCM (100 mL) solution of the compound of formula SI-28 (4.68 g, 30 mmol), NaHCO3 (2.52 g, 30 mmol), and mCPBA (85%; 9.1 g, 45 mmol) was used. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 1:1) to obtain 3.35 g of the compound of formula SI-29, with a yield of 65%.

[0068] The compound shown in formula SI-29 is a white solid with an mp value of 58-60 °C. 1 H NMR (400 MHz, CDCl3): δ3.96 (ddd, J = 9.9, 5.7, 1.9 Hz, 1H), 3.58 (s, 3H), 3.38 (s, br., 1H), 3.28 –3.14 (m, 2H), 2.39 – 2.24 (m, 1H), 2.07 – 1.92 (m, 2H), 1.86 (dddt, J = 12.6,5.5, 2.6, 1.1 Hz, 1H), 1.57 – 1.42 (m, 1H). 13 C NMR (101 MHz, CDCl3): δ174.58, 67.52, 55.43, 53.65, 51.95, 38.14, 29.91, 25.21. HRMS ( m / z ): [M+Na]+ calcd for C8H 12 NaO4 + 195.0633, found 195.0633. 5) The preparation steps are the same as step 4 in Example 1, except that MgSO4 (3.0 g, 25 mmol) and potassium azide (2.0 g, 25 mmol) were added to an aqueous (30 mL) solution of the compound of formula SI-29 (1.72 g, 10 mmol). 1.29 g of the compound of formula SI-30 was obtained, with a yield of 60%.

[0069] The compound represented by formula SI-30: a colorless oily substance. 1 H NMR (400 MHz, CDCl3): δ 3.99 (dt, J =6.6, 3.4 Hz, 1H), 3.93 – 3.84 (m, 1H), 3.71 (s, 3H), 3.56 (dd, J = 7.6, 3.0Hz, 1H), 3.03 (s, br., 2H), 2.71 (ddd, J = 11.2, 6.2, 4.9 Hz, 1H), 2.23 (tt, J = 20.5, 5.7 Hz, 2H), 1.81 (ddd, J = 14.0, 5.2, 3.5 Hz, 1H), 1.62 (ddd, J =13.6, 8.7, 4.7 Hz, 1H). 13 C NMR (126 MHz, CDCl3): δ 175.47, 73.09, 68.41,59.76, 52.21, 36.24, 31.04, 28.83. HRMS ( m / z ): [M+Na] + calcd for C8H 13 N3NaO4 + 238.0804, found 238.0802. 6) The preparation steps are the same as step 5 in Example 1, except that a DCM (30 mL) solution of the compound shown in formula SI-30 (1.3 g, 6 mmol), a DCM (30 mL) solution of Et3N (3.3 mL, 24 mmol), and a DCM (30 mL) solution of methanesulfonic anhydride (5.22 g, 30 mmol) were used. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 3:1) and crystallized (ether / methanol) to give 1.56 g of the compound shown in formula SI-31, with a yield of 70%.

[0070] The compound shown in formula SI-31 is a white solid with an mp value of 94-95 °C. 1 H NMR (400 MHz, CDCl3): δ5.00 (dt, J = 6.7, 3.2 Hz, 1H), 4.54 (d, J = 7.7 Hz, 1H), 4.20 (td, J = 8.3,4.1 Hz, 1H), 3.73 (s, 3H), 3.16 (s, 3H), 3.07 (s, 3H), 2.80 (t, J = 5.6 Hz,1H), 2.52 (s, br., 1H), 2.41 (s, br., 1H), 2.11 – 1.98 (m, 1H), 1.71 (s, br.,1H). 13 C NMR (101 MHz, CDCl3): δ 173.12, 79.18, 57.46, 52.49, 38.47, 38.46,35.17, 30.51, 28.81, 26.94. HRMS ( m / z ): [M+Na] + calcd for C 10 H 17 N3NaO8S2 + 394.0355, found 394.0355. 7) The preparation steps are the same as step 4 in Example 2, except that 30% Pd / C (110 mg) was added to a solution of the compound (372 mg, 1.0 mmol) of formula SI-31 in MeOH (5 mL) and THF (2.5 mL). The crude product was purified by silica gel rapid column chromatography (dichloromethane:methanol, 10:1) to obtain 276.0 mg of the compound of formula SI-32, with a yield of 80%.

[0071] The compound shown in formula SI-32 is a white solid with an mp value of 53-54 °C. 1 H NMR (400 MHz, CDCl3): δ5.20 (dt, J = 7.8, 3.1 Hz, 1H), 4.52 (dd, J = 7.4, 2.9 Hz, 1H), 3.72 (s, 3H), 3.60 (td, J = 7.5, 4.0 Hz, 1H), 3.17 (s, 3H), 3.07 (s, 3H), 2.87 (ddd, J =11.7, 7.0, 4.8 Hz, 1H), 2.56 – 2.42 (m, 1H), 2.28 (dd, J = 13.3, 7.3 Hz, 1H), 2.13 – 1.99 (m, 1H), 1.61 (s, 2H), 1.59 – 1.54 (m, 1H). 13 C NMR (126 MHz, CDCl3): δ 173.86, 82.07, 52.20, 50.49, 47.82, 38.50, 38.45, 35.42, 31.18,30.54. HRMS ( m / z ): [M+H] + calcd for C 10 H 20 NO8S2 + 346.0630, found 346.0628. 8) The preparation steps are the same as step 6 in Example 2, except that a THF (1.0 mL) solution of the compound of formula SI-32 (34.5 mg, 0.1 mmol) and a 0.2 mol / L PhLi diethyl ether solution (1.0 mL, 0.2 mmol) were used. The crude product of the compound of formula SI-94 was obtained. Yield: 39%.

[0072] Example 7 Preparation of Compound 12 This embodiment provides a method for preparing compound 12, the specific steps of which are as follows: ; 1) Isopropanol (20 mL) was placed in a 100 mL vial and backfilled three times with argon. Acetyl chloride (1.7 mL, 24 mmol) was added dropwise at 0 °C, and the mixture was stirred at 25 °C for 30 min under an argon atmosphere. The compound of formula SI-27 (2.5 g, 20 mmol) was added dropwise in the form of isopropanol (20 mL) solution using a syringe, and the mixture was stirred for 12 h under an argon atmosphere. The solvent was evaporated and DCM (30 mL) was added. The mixture was washed with water and brine (2 × 20 mL), and the aqueous layer was extracted with DCM (2 × 30 mL). The combined organic layers were dried over Na2SO4 and concentrated under vacuum. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate 3:1) to give 3.09 g of the compound of formula SI-33, in 84% yield.

[0073] The compound shown in formula SI-33 is a white solid with an mp value of 78-79 °C. 1 H NMR (400 MHz, CDCl3): δ5.74 (s, 2H), 5.00 (hept, J = 6.3 Hz, 1H), 4.27 (ddt, J = 7.8, 5.9, 3.0 Hz,1H), 2.65 (dtd, J = 10.5, 7.2, 3.2 Hz, 1H), 2.26 (ddt, J = 8.1, 4.7, 3.1 Hz,3H), 1.71 (ddd, J = 12.9, 10.6, 7.9 Hz, 1H), 1.22 (dd, J = 6.3, 2.9 Hz, 6H). 13 C NMR (101 MHz, CDCl3): δ 174.82, 130.87, 126.87, 67.97, 66.00, 38.07,34.14, 27.42, 21.74. HRMS ( m / z ): [M+H] + calcd for C 10 H 17 O3 + 185.1178, found 185.1176. 2) The preparation steps are the same as step 3 in Example 1, except that: a DCM (30 mL) solution of the compound of formula SI-33 (1.84 g, 10 mmol), a NaHCO3 (840 mg, 10 mmol) solution, and a DCM (60 mL) solution of mCPBA (85%; 3.0 g, 15 mmol) were used. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 1:1) to obtain 1.34 g of the compound of formula SI-34, with a yield of 67%.

[0074] The compound shown in formula SI-34 is a white solid with a mp value of 47-49 °C. 1 H NMR (400 MHz, CDCl3): δ4.95 (hept, J = 6.3 Hz, 1H), 4.02 (ddd, J = 9.4, 5.8, 2.1 Hz, 1H), 3.42 –3.17 (m, 2H), 2.85 (s, br., 1H), 2.45 – 2.22 (m, 1H), 2.05 (ddd, J = 7.5,4.3, 1.4 Hz, 2H), 1.90 (ddd, J = 12.9, 5.8, 2.9 Hz, 1H), 1.58 (ddd, J = 12.9,11.5, 9.3 Hz, 1H), 1.18 (dd, J = 6.3, 3.9 Hz, 6H). 13 C NMR (101 MHz, CDCl3): δ173.67, 68.13, 67.53, 55.36, 53.85, 38.42, 30.17, 25.34, 21.68. HRMS ( m / z ):[M+Na] + calcd for C 10 H 16 NaO4 + 223.0946, found 223.0944. ; 3) The preparation steps are the same as step 4 in Example 1, except that MgSO4 (4.8 g, 40 mmol) and potassium azide (4.24 g, 40 mmol) were added to an aqueous (30 mL) solution of the compound of formula SI-34 (1.98 g, 10 mmol). This yielded 1.46 g of the compound of formula SI-35, with a yield of 60%.

[0075] The compound represented by formula SI-35: a colorless oily substance. 1 H NMR (400 MHz, CDCl3): δ 5.01 (hept, J = 6.3 Hz, 1H), 3.99 (ddd, J = 8.2, 6.4, 3.6 Hz, 1H), 3.89 – 3.80 (m, 1H), 3.64 – 3.47 (m, 1H), 3.08 (d, J = 4.8 Hz, 1H), 2.91 (d, J = 5.4 Hz, 1H), 2.67(p, J = 5.6 Hz, 1H), 2.38 – 2.07 (m, 2H), 1.80 (ddd, J = 14.1, 5.3, 3.7 Hz,1H), 1.62 (ddd, J = 13.7, 8.8, 4.8 Hz, 1H), 1.24 (d, J = 6.3 Hz, 6H). 13 C NMR (101 MHz, CDCl3): δ 174.68, 73.21, 68.62, 68.41, 59.85, 36.74, 30.95, 29.03,21.70, 21.66. HRMS ( m / z ): [M+Na] + calcd for C 10 H 17 N3NaO4 + 226.1117, found 226.1117. 4) The preparation steps are the same as step 5 in Example 1, except that a DCM (30 mL) solution of the compound shown in formula SI-35 (1.46 g, 6 mmol), a DCM (30 mL) solution of Et3N (3.3 mL, 24 mmol), and a DCM (30 mL) solution of methanesulfonic anhydride (5.22 g, 30 mmol) were used. The crude product was purified by silica gel rapid column chromatography (dichloromethane:diethyl ether, 100:1) to obtain 1.75 g of the compound shown in formula SI-36, with a yield of 73%.

[0076] The compound represented by formula SI-36: a colorless oil. 1 H NMR (500 MHz, CDCl3): δ 5.08 – 4.92(m, 2H), 4.67 – 4.56 (m, 1H), 4.22 (td, J = 7.0, 3.8 Hz, 1H), 3.15 (s, 3H), 3.07 (s, 3H), 2.78 – 2.68 (m, 1H), 2.32 (d, J = 36.3 Hz, 2H), 2.08 (dt, J =14.4, 4.3 Hz, 1H), 1.80 (d, J = 12.6 Hz, 1H), 1.25 (dd, J = 9.7, 6.3 Hz, 6H). 13 C NMR (126 MHz, CDCl3): δ 172.12, 78.37, 76.36, 69.20, 58.07, 38.56, 38.47,35.63, 30.01, 28.21, 21.73, 21.65. HRMS ( m / z ): [M+Na] + calcd for C 12 H 21 N3NaO8S2 + 422.0668, found 422.0668. ; 5) The preparation steps are the same as step 4 in Example 2, except that 30% Pd / C (120 mg) was added to a solution of the compound (400 mg, 1.0 mmol) of formula SI-36 in MeOH (5 mL) and THF (2.5 mL). The crude product was purified by silica gel rapid column chromatography (dichloromethane:methanol, 10:1) to obtain 298.4 mg of the compound of formula SI-37, with a yield of 80%.

[0077] The compound represented by formula SI-37: a colorless oil. 1 H NMR (400 MHz, CDCl3): δ 5.20 (dt, J =8.8, 3.4 Hz, 1H), 4.98 (hept, J = 6.3 Hz, 1H), 4.57 (dd, J = 6.3, 3.0 Hz, 1H), 3.58 (td, J = 6.4, 3.8 Hz, 1H), 3.13 (s, 3H), 3.06 (s, 3H), 2.82 (tt, J = 8.8, 4.6 Hz, 1H), 2.32 (dt, J = 17.0, 8.9 Hz, 1H), 2.21 – 2.11 (m, 1H), 2.07 (dt, J = 13.6, 4.3 Hz, 1H), 1.61 (dt, J = 14.0, 5.3 Hz, 1H), 1.50 (s,2H), 1.23 (t, J = 6.3 Hz, 6H). 13 C NMR (126 MHz, CDCl3): δ 172.91, 81.54,76.58, 68.66, 48.48, 38.58, 38.56, 35.79, 30.64, 30.15, 21.74, 21.71. HRMS( m / z ): [M+H] + calcd for C 12 H 24 NO8S2 + 374.0943, found 374.0942. 6) The preparation steps are the same as step 6 in Example 2, except that a THF (1.0 mL) solution of the compound of formula SI-37 (37.3 mg, 0.1 mmol) and a 0.2 mol / L PhLi diethyl ether solution (1.0 mL, 0.2 mmol) were used. The crude product of the compound of formula 12 was obtained. Yield: 43%.

[0078] The compound shown in Formula 12: 1 H NMR (400 MHz, CDCl3): δ 5.02 (tt, J= 11.9, 6.2 Hz, 1H), 3.15 (dd, J = 6.3, 2.1 Hz, 1H), 3.12 – 3.09 (m, 2H), 2.58 (p, J = 1.9Hz, 1H), 2.05 (ddd, J = 15.3, 4.8, 2.5 Hz, 2H), 1.84 – 1.77 (m, 2H), 1.24 (d, J = 6.3 Hz, 6H). Example 8 Preparation of compounds 15-63 , ; This embodiment provides a method for preparing the compounds shown in Formulas 15-65 and SI-93, SI-93, as follows: 1) TosCl (38.0 mg, 0.2 mmol) was added to a MeCN (1.0 mL) solution of the compound shown in Formula 10 (19.6 mg, 0.1 mmol) at 0 °C, and the reaction mixture was stirred at 25 °C for 12 hours under an argon atmosphere. After the reaction was complete, the reaction mixture was concentrated under vacuum, the residue was diluted with water, extracted with DCM (3 × 1.0 mL), the combined organic layers were washed with brine and dried with Na2SO4, the solvent was removed under reduced pressure, and the crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 5:1) to give 25.5 mg of the compound shown in Formula 15, in 66% yield.

[0079] The compound shown in Formula 15 is a white solid with a mp value of 150-151 °C. 1 H NMR (400 MHz, CDCl3): δ7.78 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 7.9 Hz, 2H), 4.78 (t, J = 6.2 Hz, 1H), 4.50 – 4.39 (m, 2H), 3.75 (ddd, J = 13.0, 8.0, 2.6 Hz, 2H), 3.66 (ddd, J =12.6, 5.5, 1.4 Hz, 2H), 2.45 (s, 3H), 1.46 (s, 9H). 13C NMR (101 MHz, CDCl3): δ 154.86, 144.75, 135.62, 130.06, 127.61, 80.31, 64.76, 64.55, 50.47, 44.78,44.21, 28.42, 21.66. HRMS ( m / z ): [M+Na] + calcd for C 17 H 23 ClN2NaO4S + 409.0965, found 409.0964. 2) The method is the same as in step 1), except that TosBr (35.3 mg, 0.15 mmol) was added to a DCM (1.0 mL) solution of the compound shown in Formula 1 (23 mg, 0.1 mmol) at 0 °C. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 3:1) to give 26.9 mg of the compound shown in Formula 16, with a yield of 58%.

[0080] The compound shown in Formula 16 is a white solid with a mp value of 131-133 °C. 1 H NMR (400 MHz, CDCl3): δ7.81 – 7.73 (m, 2H), 7.41 – 7.27 (m, 7H), 5.16 (s, 2H), 4.94 (t, J = 6.2 Hz, 1H), 4.48 (ddddd, J = 14.0, 6.4, 4.8, 2.7, 1.7 Hz, 2H), 3.87 (td, J = 12.1,2.7 Hz, 2H), 3.79 (ddd, J = 12.8, 4.7, 1.7 Hz, 2H), 2.44 (s, 3H). 13 C NMR (101MHz, CDCl3): δ 155.43, 144.85, 136.39, 135.46, 130.07, 128.54, 128.13,127.83, 127.62, 67.35, 64.21, 63.97, 45.91, 45.78, 41.28, 21.64. HRMS ( m / z ):[M+Na] + calcd for C 20 H 21BrN2NaO4S + 487.0303, found 487.0304. 3) The method is the same as in step 1), except that the compound shown in formula 2 (9.5 mg, 0.1 mmol) is used instead of the compound shown in formula 10. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 18.9 mg of the compound shown in formula 17, with a yield of 66%.

[0081] The compound shown in Formula 17 is a white solid with a mp value of 81-82 °C. 1 H NMR (500 MHz, CDCl3): δ 7.79(d, J = 8.3 Hz, 2H), 7.33 (d, J = 8.1 Hz, 2H), 4.56 (t, J = 6.3 Hz, 1H), 4.38(dq, J = 6.0, 4.0 Hz, 2H), 2.44 (s, 3H), 2.13 (ddt, J = 13.4, 9.2, 3.6 Hz,2H), 2.02 (ddd, J = 14.4, 9.2, 6.2 Hz, 2H), 1.94 – 1.78 (m, 2H). 13 C NMR (126MHz, CDCl3): δ 144.18, 136.32, 129.98, 127.43, 68.07, 53.45, 23.10, 21.62,13.72. HRMS ( m / z ): [M+Na] + calcd for C 13 H 16 ClNNaO2S + 308.0488, found 308.0486. 4) TosBr (23.5 mg, 0.1 mmol) was added to the crude product of the compound of formula SI-96 obtained in Example 6 or the crude product of the compound of formula 12 obtained in Example 7. The mixture was then stirred at 25 °C for 18 hours and evaporated under vacuum. The residue was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 5:1) to give 9.1 mg of the compound of formula 18 (60% yield) and 11.6 mg of the compound of formula 19 (65% yield).

[0082] The compound shown in Formula 18 is a white solid with a mp value of 142-144 °C. 1 H NMR (500 MHz, CDCl3): δ7.79 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 7.8 Hz, 2H), 4.76 (t, J = 6.4 Hz, 1H), 4.44 (t, J = 5.4 Hz, 2H), 3.72 (s, 3H), 3.17 (p, J = 9.1 Hz, 1H), 2.55 – 2.38(m, 7H). 13 C NMR (126 MHz, CDCl3): δ 174.20, 144.52, 135.95, 130.10, 127.44,66.67, 52.08, 46.70, 32.39, 26.90, 21.65. HRMS ( m / z ): [M+Na] + calcd forC 15 H 18 BrNNaO4S + 410.0038, found 410.0039. The compound shown in Formula 19 is a white solid with a mp value of 127-128 °C. 1 H NMR (400 MHz, CDCl3): δ7.79 (d, J = 8.3 Hz, 2H), 7.35 (d, J = 7.9 Hz, 2H), 5.05 (hept, J = 6.3 Hz, 1H), 4.78 (t, J = 6.3 Hz, 1H), 4.48 – 4.41 (m, 2H), 3.11 (p, J = 9.1 Hz, 1H),2.55 – 2.36 (m, 7H), 1.24 (d, J = 6.2 Hz, 6H). 13C NMR (101 MHz, CDCl3): δ173.24, 144.46, 136.01, 130.07, 127.45, 68.16, 66.76, 46.75, 32.61, 26.94,21.81, 21.65. HRMS ( m / z ): [M+Na] + calcd for C 17 H 22 BrNNaO4S + 438.0351, found 438.0349. 5) The method is the same as in step 1), except that the compound shown in formula 3 (8.1 mg, 0.1 mmol) is used instead of the compound shown in formula 10. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 17.9 mg of the compound shown in formula 20, with a yield of 66%.

[0083] The compound shown in Formula 20 is a white solid with an mp value of 85-86 °C. 1 H NMR (500 MHz, CDCl3): δ 7.75(d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 4.35 – 4.33 (m, 2H), 4.29 (tt, J = 2.8, 1.3 Hz, 1H), 2.43 (s, 3H), 2.26 – 2.20 (m, 2H), 2.07 – 2.02 (m, 2H). 13 C NMR (126 MHz, CDCl3): δ 144.04, 137.35, 129.65, 127.34, 72.38, 53.51,23.79, 21.60. HRMS ( m / z ): [M+Na] + calcd for C 12 H 14 ClNNaO2S + 294.0331, found294.0334. 6) TosCl (95 mg, 0.5 mmol) was added to the crude product of the compound of formula 4 obtained in Example 4, and the mixture was then stirred at 25 °C for 18 hours and evaporated under vacuum. The residue was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 9.0 mg of the compound of formula 21 in 60% yield.

[0084] The compound shown in Formula 21 is a white solid with a mp value of 131-132 °C. 1 H NMR (400 MHz, CDCl3): δ7.81 (d, J = 8.3 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 4.47 – 4.40 (m, 2H), 4.38 – 4.29 (m, 1H), 2.46 (s, 3H), 2.02 – 1.82 (m, 8H). 13 C NMR (101 MHz, CDCl3): δ144.22, 134.95, 130.03, 127.51, 67.79, 52.54, 27.92, 23.15, 21.64. HRMS ( m / z ): [M+Na] + calcd for C 14 H 18 ClNNaO2S + 322.0644, found 322.0645. 7) The method is the same as in step 1), except that LiBr (2.18 g, 25 mmol) and Boc2O (2.18 g, 10 mmol) were added to a MeCN (50 mL) solution of the compound shown in Formula 1 (1.15 g, 5 mmol) at 0 °C. The crude product was purified by silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 1.77 g of the compound shown in Formula 22, with a yield of 86%.

[0085] The compound shown in Formula 22 is a white solid with an mp value of 98-99 °C. 1 H NMR (500 MHz, CDCl3): δ 7.38– 7.27 (m, 5H), 5.20 (d, J = 12.5 Hz, 1H), 5.14 (d, J = 12.4 Hz, 1H), 4.66(t, J= 5.9 Hz, 1H), 4.29 (dt, J = 6.4, 3.5 Hz, 1H), 4.23 (dt, J = 6.6, 3.5Hz, 1H), 4.18 – 4.08 (m, 2H), 3.57 – 3.50 (m, 2H), 1.40 (s, 9H). 13 C NMR (126MHz, CDCl3): δ 155.83, 155.77, 136.56, 128.51, 128.04, 127.79, 81.53, 67.19,62.45, 62.07, 42.53, 42.20, 40.88, 28.09. HRMS ( m / z ): [M+Na] + calcd forC 18 H 23 BrN2NaO4 + 433.0739, found 433.0737. 8) The method is the same as in step 7), except that the compound shown in Formula 1 is replaced with the compound shown in Formula 2 (950 mg, 10 mmol), and LiBr (4.34 g, 50 mmol) and Boc2O (4.36 g, 20 mmol) are used. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 20:1) to give 2.18 g of the compound shown in Formula 23, with a yield of 79%.

[0086] The compound shown in Formula 23: 1 H NMR (500 MHz, CDCl3): δ 4.71 (t, J = 6.0 Hz, 1H), 4.23 (s, 2H), 2.28 (s, br., 2H), 1.91 (t, J = 8.4 Hz, 1H), 1.94 (t, J = 8.2Hz, 1H), 1.81 – 1.70 (m, 1H), 1.64 – 1.51 (m, 1H), 1.47 (s, 9H). 9) The method is the same as in step 8), except that the compound shown in Formula 2 is replaced with the compound shown in Formula 3 (8.1 mg, 0.1 mmol), and LiBr (54.2 mg, 0.5 mmol) and Boc2O (43.6 mg, 0.2 mmol) are added. 21.7 mg of the compound shown in Formula 24 is obtained, with a yield of 83%.

[0087] The compound shown in Formula 24: 1 H NMR (500 MHz, CDCl3): δ 4.22 (d, J = 2.8 Hz, 2H), 4.13 (tt, J = 2.8, 1.3 Hz, 1H), 2.01 (d, J = 8.6 Hz, 2H), 1.91 (d, J = 9.0Hz, 2H), 1.44 (s, 9H). 10) The method is the same as in step 1), except that CbzCl (34 mg, 0.2 mmol) is used instead of TosCl. 21.2 mg of the compound shown in Formula 25 is obtained, with a yield of 58%.

[0088] The compound shown in Formula 25: 1 H NMR (500 MHz, CDCl3): δ 7.40 – 7.30 (m, 5H), 5.15(d, J = 12.2 Hz, 1H), 5.10 (d, J = 12.2 Hz, 1H), 4.62 (t, J = 5.9 Hz, 1H), 4.39 (dt, J = 6.4, 3.5 Hz, 1H), 4.32 (dt, J = 6.5, 3.5 Hz, 1H), 4.01 – 3.95(m, 2H), 3.45 (dd, J = 12.8, 6.8 Hz, 2H), 1.47 (s, 9H). 11) The method is the same as in step 1), except that the compound shown in formula 2 (19 mg, 0.2 mmol) is used instead of the compound shown in formula 10, and CbzCl (68 mg, 0.4 mmol) is used instead of TosCl. 38.1 mg of the compound shown in formula 26 is obtained, with a yield of 72%.

[0089] The compound shown in Formula 26, 1 H NMR (500 MHz, CDCl3): δ 7.40 – 7.29 (m, 5H), 5.14(s, 2H), 4.64 (t, J= 6.0 Hz, 1H), 4.35 – 4.32 (m, 2H), 2.19 (s, br., 2H), 1.92 (t, J = 7.0 Hz, 1H), 1.89 (t, J = 6.0 Hz, 1H), 1.78 – 1.68 (m, 1H), 1.50(dddd, J = 14.6, 9.8, 7.3, 2.3 Hz, 1H). 12) The method is the same as in step 1), except that the compound shown in Formula 2 (9.5 mg, 0.1 mmol) is used instead of the compound shown in Formula 10, and acetyl bromide (40.2 mg, 0.2 mmol) is used instead of TosCl. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:1) to give 11.3 mg of the compound shown in Formula 27, with a yield of 52%.

[0090] The compound shown in Formula 27: 1 H NMR (500 MHz, CDCl3): δ 4.76 (t, J = 6.1 Hz, 1H), 4.51 (q, J = 4.8 Hz, 1H), 4.39 (q, J = 4.8 Hz, 1H), 2.32 (dt, J = 12.6, 7.7Hz, 1H), 2.18 – 2.05 (m, 2H), 1.99 – 1.91 (m, 4H), 1.87 – 1.77 (m, 1H), 1.68– 1.57 (m, 1H). 13) LiAlH4 (7.6 mg, 0.2 mmol) was added to a THF (0.5 mL) solution of the compound shown in Formula 2 (9.5 mg, 0.1 mmol) at 0 °C, and the reaction mixture was stirred at 25 °C for 3 hours under an argon atmosphere. Then, Boc2O (43.6 mg, 0.2 mmol) and K2CO3 (27.6 mg, 0.2 mmol) were added at 0 °C. The steps after the reaction were the same as in step 1). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 20:1) to give 10.2 mg of the compound shown in Formula 28, in 52% yield.

[0091] The compound shown in Formula 28, 1H NMR (400 MHz, CDCl3): δ 4.07 (s, br., 2H), 2.42(dtt, J = 7.8, 6.3, 1.5 Hz, 1H), 2.33 (s, br., 1H), 2.20 (s, br., 1H), 1.98 –1.84 (m, 1H), 1.74 – 1.59 (m, 3H), 1.46 (s, 9H), 1.36 (d, J = 8.7 Hz, 1H). 14) The method is the same as in step 13), except that LiAlD4 (8.4 mg, 0.2 mmol) is used instead of LiAlH4 to obtain 8.3 mg of the compound shown in Formula 29, with a yield of 42%.

[0092] The compound shown in Formula 29: 1 H NMR (500 MHz, CDCl3): δ 4.06 (s, 2H), 2.40 (t, J =6.4 Hz, 1H), 2.27 (s, 2H), 1.96 – 1.85 (m, 1H), 1.72 – 1.61 (m, 3H), 1.45 (s, 9H). 15) At 0 °C, Boc₂O (43.6 mg, 0.2 mmol) and TMSCN (49.5 mg, 0.5 mmol) were added to a MeCN (0.5 mL) solution of the compound shown in Formula 2 (9.5 mg, 0.1 mmol), and the reaction mixture was stirred at 25 °C for 12 hours under an argon atmosphere. The steps after the reaction were completed were the same as in step 1). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 10.4 mg of the compound shown in Formula 30, in 47% yield.

[0093] The compound shown in Formula 30: 1 H NMR (400 MHz, CDCl3): δ 4.28 (s, br. 2H), 3.50 –3.42 (m, 1H), 2.40 (s, br., 2H), 2.06 – 1.88 (m, 3H), 1.75 – 1.62 (m, 1H),1.47 (s, 9H). 16) At 0 °C, Cu(OTf)₂ (3.6 mg, 0.01 mmol) and iPr·MgCl·LiCl (1.0 M, THF, 0.1 mL, 0.1 mmol) were added to a THF (0.5 mL) solution of the compound shown in Formula 2 (9.5 mg, 0.1 mmol), and the reaction mixture was stirred at 25 °C for 3 hours under an argon atmosphere. Then, Boc₂O (43.6 mg, 0.2 mmol) and K₂CO₃ (27.6 mg, 0.2 mmol) were added at 0 °C. After the reaction was complete, the reaction mixture was concentrated under vacuum. The residue was diluted with saturated aqueous solution. The reaction mixture was quenched with NH₄Cl (0.5 mL) and extracted with DCM (3 × 0.5 mL). The combined organic layers were washed with brine and dried with Na₂SO₄. The solvent was removed under reduced pressure, and the crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 20:1) to give 18.4 mg of the compound shown in Formula 31, with a yield of 77%.

[0094] The compound shown in Formula 31: 1 H NMR (500 MHz, CDCl3): δ 4.02 (s, 1H), 3.97 (s, 1H), 2.24 (s, br., 1H), 2.17 – 2.06 (m, 2H), 1.73 – 1.64 (m, 2H), 1.62 – 1.54 (m,3H), 1.45 (s, 9H),0.81 (d, J = 5.2 Hz, 6H). 17) The method is the same as in step 1), except that the compound shown in Formula 1 (23.0 mg, 0.1 mmol) is used instead of the compound shown in Formula 10, and Ac2O (41.4 mg, 0.3 mmol) is used instead of TosCl. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:2) to give 12.9 mg of the compound shown in Formula 32, with a yield of 39%.

[0095] The compound shown in Formula 32: 1 H NMR (500 MHz, CDCl3): δ 7.43 – 7.29 (m, 5H), 5.23 –5.10 (m, 3H), 4.72 – 4.48 (m, 2H), 4.16 – 4.02 (m, 1H), 3.93 – 3.83 (m, 1H), 3.49 – 3.37 (m, 2H), 2.09 – 2.01 (m, 3H), 2.00 – 1.89 (m, 3H). 18) K₂CO₃ (41.4 mg, 0.3 mmol) and Boc₂O (43.6 mg, 0.2 mmol) were added to a MeCN (1.0 mL) solution of the compound shown in Formula 2 (9.5 mg, 0.1 mmol) at 0 °C, and the reaction mixture was stirred at 25 °C for 12 hours under an argon atmosphere. The subsequent steps after the reaction were the same as in step 1). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 20.7 mg of the compound shown in Formula 33, in 66% yield.

[0096] The compound shown in Formula 33: 1 H NMR (400 MHz, CDCl3): δ 4.89 (t, J = 5.9 Hz, 1H), 4.29 (s, br., 2H), 2.18 (s, br., 2H), 1.82 – 1.63 (m, 3H), 1.59 – 1.51 (m,1H), 1.49 (s, 9H), 1.47 (s, 9H). 19) At 0 °C, HBr (48%, 337.1 mg, 2.0 mmol) was added to a 20 mL MeOH solution of the compound shown in Formula 1 (460 mg, 2 mmol), and the reaction mixture was stirred at 25 °C for 12 hours under an argon atmosphere. Then, Boc₂O (872.4 mg, 4.0 mmol) and K₂CO₃ (552.2 mg, 4.0 mol) were added at 0 °C. The procedure after the reaction was completed was the same as in step 1). 514.0 mg of the compound shown in Formula 34 was obtained, with a yield of 71%.

[0097] The compound shown in Formula 34: 1 H NMR (500 MHz, CDCl3): δ 7.39 – 7.26 (m, 5H), 5.17(d, J = 12.5 Hz, 1H), 5.11 (d, J = 12.4 Hz, 1H), 4.24 (s, 1H), 4.19 (s, 1H), 4.04 (s, br., 2H), 4.00 (t, J = 5.6 Hz, 1H), 3.34 (s, 3H), 3.29 (t, J = 12.7Hz, 2H), 1.38 (s, 9H). 20) At -35 °C, TfOH (0.2 mol / L, MeCN solution, 0.5 mL, 0.1 mmol) and phenylpropanol (27.2 mg, 0.2 mmol) were added to a MeCN (1.0 mL) solution of the compound shown in Formula 1 (23 mg, 0.1 mmol), and the reaction mixture was stirred at 25 °C for 12 hours under an argon atmosphere. Then, Boc2O (43.6 mg, 0.2 mmol) and DIPEA (25.8 mg, 0.2 mmol) were added at 0 °C. The steps after the reaction were the same as in step 1). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 3:1) to give 14.4 mg of the compound shown in Formula 35, in 31% yield.

[0098] The compound shown in Formula 35: 1 H NMR (500 MHz, CDCl3): δ 7.37 – 7.24 (m, 7H), 7.20 –7.13 (m, 3H), 5.21 – 5.10 (m, 2H), 4.22 (s, 1H), 4.17 (s, 1H), 4.08 – 4.04(m, 3H), 3.45 (td, J = 6.5, 3.5 Hz, 2H), 3.36 – 3.29 (m, 2H), 2.68 – 2.62 (m,2H), 1.89 (dq, J = 8.4, 6.5 Hz, 2H), 1.39 (s, 9H). 21) Phenol (18.8 mg, 0.2 mmol) was added to a 1.0 mL toluene solution of the compound shown in Formula 2 (9.5 mg, 0.1 mmol) at 25 °C, and the reaction mixture was stirred at 25 °C for 12 hours under an argon atmosphere. Then, Boc₂O (43.6 mg, 0.2 mmol) and K₂CO₃ (27.6 mg, 0.2 mmol) were added at 0 °C. The procedure after the reaction was completed was the same as in step 1). 20.5 mg of the compound shown in Formula 36 was obtained, with a yield of 71%.

[0099] The compound shown in Formula 36: 1 H NMR (400 MHz, CDCl3): δ 7.33 – 7.26 (m, 2H), 6.98(t, J = 7.3 Hz, 1H), 6.87 (d, J = 8.1 Hz, 2H), 4.72 (t, J= 5.7 Hz, 1H), 4.41(s, br., 2H), 2.16 (s, br., 2H), 1.86 – 1.71 (m, 3H), 1.57 (s, 1H), 1.49 (s,9H). 22) The method is the same as in step 21), except that the compound shown in Formula 2 is replaced with the compound shown in Formula 1 (23 mg, 0.1 mmol). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 3:1) to give 20.8 mg of the compound shown in Formula 37, with a yield of 49%.

[0100] The compound shown in Formula 37: 1 H NMR (500 MHz, CDCl3): δ 7.36 – 7.25 (m, 7H), 7.01(t, J = 7.4 Hz, 1H), 6.85 (d, J = 7.9 Hz, 2H), 5.18 (d, J = 12.5 Hz, 1H), 5.12 (d, J = 12.4 Hz, 1H), 4.80 (t, J = 5.6 Hz, 1H), 4.46 (s, br., 1H), 4.41(s, br., 1H), 4.11 (s, br., 2H), 3.39 (dd, J = 12.4, 5.4 Hz, 2H), 1.41 (s,9H). 23) The method is the same as in step 21), except that benzoic acid (18.3 mg, 0.15 mmol) is used instead of phenol. 25.7 mg of the compound shown in Formula 38 is obtained, with a yield of 81%.

[0101] The compound shown in Formula 38: 1 H NMR (500 MHz, CDCl3): δ 8.08 – 8.03 (m, 2H), 7.64 –7.57 (m, 1H), 7.48 (t, J = 7.8 Hz, 2H), 5.29 (t, J = 5.9 Hz, 1H), 4.43 (s,2H), 2.27 (s, br., 2H), 1.85 – 1.76 (m, 3H), 1.70 – 1.60 (m, 1H), 1.49 (s,9H). 24) The method is the same as in step 22), except that the compound shown in Formula 1 (46 mg, 0.2 mmol), Boc2O (87.2 mg, 0.4 mmol), and K2CO3 (55.2 mg, 0.4 mmol) are used, and benzoic acid (36.6 mg, 0.3 mmol) is used instead of phenol. This yields 78.6 mg of the compound shown in Formula 39, representing 87% of the total.

[0102] The compound shown in Formula 39: 1 H NMR (500 MHz, CDCl3): δ 7.95 (dd, J = 8.4, 1.4 Hz, 2H), 7.60 (tt, J = 7.1, 1.3 Hz, 1H), 7.44 (t, J = 7.8 Hz, 2H), 7.35 – 7.27(m, 5H), 5.37 (t, J = 5.8 Hz, 1H), 5.17 (d, J = 12.5 Hz, 1H), 5.13 (d, J =12.4 Hz, 1H), 4.48 (s, br. 1H), 4.44 (s, br. 1H), 4.28 – 4.09 (m, 2H), 3.45(d, J = 12.7 Hz, 1H), 3.40 (d, J = 12.5 Hz, 1H), 1.42 (s, 9H). 25) The method is the same as in step 21), except that dibenzyl phosphate (55.6 mg, 0.2 mmol) is used instead of phenol. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 3:1) to give 20.8 mg of the compound shown in Formula 40, with a yield of 44%.

[0103] The compound shown in Formula 40: 1 H NMR (500 MHz, CDCl3): δ 7.41 – 7.31 (m, 10H), 5.12 –5.01 (m, 4H), 4.71 (q, J = 6.0 Hz, 1H), 4.08 (s, br. 2H), 2.06 (s, br., 2H), 1.71 – 1.57 (m, 4H), 1.44 (s, 9H). 26) The method is the same as in step 21), except that 4-methoxybenzylthiol (28.0 mg, 0.2 mmol) is added instead of phenol to a THF (1.0 mL) solution of the compound shown in Formula 2 (9.5 mg, 0.1 mmol) at 0 °C. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 18.5 mg of the compound shown in Formula 41, with a yield of 58%.

[0104] The compound shown in Formula 41: 1 H NMR (500 MHz, CDCl3): δ 7.22 – 7.16 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 7.9 Hz, 2H), 4.27 (s, br. 2H), 4.08 (t, J = 6.1 Hz, 1H), 2.31 (s, 3H), 2.19 (s, br., 2H), 1.92 – 1.84 (m, 2H), 1.78 – 1.83 (m, 1H), 1.58 – 1.67 (m, 1H), 1.47 (s, 9H). 27) The method is the same as in step 26), except that 2-benzothiazolium (28.0 mg, 0.2 mmol) is used instead of 4-methoxybenzylthiol. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 3:1) to give 23.9 mg of the compound shown in Formula 42, with a yield of 66%.

[0105] The compound shown in Formula 42: 1 H NMR (500 MHz, CDCl3): δ 7.86 (d, J = 8.1 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.31 (t, J = 7.6 Hz, 1H), 4.80 (t, J = 6.2 Hz, 1H), 4.46 (s, 2H), 2.35 (s, br., 1H), 2.28 (s, br., 1H), 1.86 – 1.75 (m, 3H), 1.69 – 1.60 (m, 1H), 1.49 (s, 9H). 28) 1-Hexamethylenetetramol (23.6 mg, 0.2 mmol) was added to a THF (1.0 mL) solution of the compound shown in Formula 2 (9.5 mg, 0.1 mmol) at 0 °C, and the reaction mixture was stirred at 25 °C for 12 hours under an argon atmosphere. Then, TosCl (38.0 mg, 0.2 mmol) was added at 0 °C, and the mixture was stirred again at 25 °C for 3 hours. The steps after the reaction were the same as in step 1). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 22.7 mg of the compound shown in Formula 43, in 62% yield.

[0106] The compound shown in Formula 43: 1 H NMR (500 MHz, CDCl3): δ 7.82 (d, J = 8.2 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 4.33 – 4.26 (m, 2H), 3.58 (t, J = 6.4 Hz, 1H), 2.44(s, 3H), 2.30 (t, J = 7.4 Hz, 2H), 2.17 – 2.08 (m, 2H), 1.98 – 1.77 (m, 4H), 1.42 – 1.31 (m, 2H), 1.33 – 1.18 (m, 6H), 0.89 (t, J = 7.1 Hz, 3H). 29) The method is the same as in step 26), except that 4-methoxybenzylthiol (28.0 mg, 0.2 mmol) is used instead of selenoyl alcohol. 21.8 mg of the compound shown in Formula 44 is obtained, with a yield of 62%.

[0107] The compound shown in Formula 44: 1 H NMR (500 MHz, CDCl3): δ 7.47 – 7.41 (m, 2H), 7.27 –7.24 (m, 3H), 4.28 (s, 2H), 4.25 (dd, J = 12.4, 6.9 Hz, 1H), 2.30 (s, br.,2H), 1.93 – 1.83 (m, 2H), 1.84 – 1.73 (m, 1H), 1.70 – 1.57 (m, 1H), 1.47 (s,9H). 30) The method is the same as in step 1), except that the compound shown in formula 2 (19 mg, 0.2 mmol) is used instead of the compound shown in formula 10, and CbzN3 (70.8 mg, 0.4 mmol) is used instead of TosCl. 30.5 mg of the compound shown in formula 45 is obtained, with a yield of 56%.

[0108] The compound shown in Formula 45: 1 H NMR (400 MHz, CDCl3): δ 7.42 – 7.27 (m, 5H), 5.13 (s, 2H), 4.38 – 4.28 (m, 3H), 2.14 (s, br., 2H), 1.81 – 1.68 (m, 3H), 1.49 –1.41 (m, 1H). 31) At -35 °C, TfOH (0.2 mol / L, MeCN solution, 0.5 mL, 0.1 mmol) and benzylamine (21.4 mg, 0.2 mmol) were added to a MeCN (1.0 mL) solution of the compound shown in Formula 2 (9.5 mg, 0.1 mmol), and the reaction mixture was stirred at 25 °C for 3 hours under an argon atmosphere. Then, Boc2O (43.6 mg, 0.2 mmol) and K2CO3 (27.6 mg, 0.2 mmol) were added at 0 °C. The procedure after the reaction was completed was the same as in step 1). 10.3 mg of the compound shown in Formula 46 was obtained, with a yield of 34%.

[0109] The compound shown in Formula 46: 1 H NMR (400 MHz, CDCl3): δ 7.36 – 7.23 (m, 5H), 4.12(s, 1H), 4.07 (s, 1H), 3.73 (s, 2H), 3.56 (t, J = 6.0 Hz, 1H), 2.21 (s, br.,1H), 2.08 (s, br., 1H), 1.73 – 1.53 (m, 5H), 1.46 (s, 9H). 32) The method is the same as in step 31), except that morpholine (17.4 mg, 0.2 mmol) is used instead of benzylamine. 19.7 mg of the compound shown in Formula 47 is obtained, with a yield of 70%.

[0110] The compound shown in Formula 47: 1 H NMR (500 MHz, CDCl3): δ 4.09 (s, 1H), 4.03 (s, 1H), 3.70 (t, J= 4.7 Hz, 4H), 2.83 (t, J = 5.8 Hz, 1H), 2.29 – 2.23 (m, 4H), 2.12(s, br., 1H), 1.98 (s, br., 1H), 1.88 – 1.77 (m, 1H), 1.74 – 1.63 (m, 2H),1.56 – 1.48 (m, 1H), 1.46 (s, 9H). 33) The method is the same as in step 31), except that 4-phenylpiperidine (32.2 mg, 0.2 mmol) is used instead of benzylamine. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 27.8 mg of the compound shown in Formula 48, with a yield of 78%.

[0111] The compound shown in Formula 48: 1 H NMR (400 MHz, CDCl3): δ 7.25 (t, J = 7.5 Hz, 2H), 6.92 (d, J = 8.2 Hz, 2H)., 6.86 (t, J = 7.3 Hz, 1H), 4.13 (s, 1H), 4.08 (s,1H), 3.20 (t, J = 5.0 Hz, 4H), 2.89 (t, J = 5.8 Hz, 1H), 2.43 (t, J = 5.0 Hz,4H), 2.15 (s, br., 1H), 2.01 (s, br., 1H), 1.68 – 1.89 (m, 3H), 1.61 – 1.49(m, 1H), 1.48 (s, 9H). 34) The method is the same as in step 33), except that aniline (18.6 mg, 0.2 mmol) is used instead of 4-phenylpiperidine. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 22.8 mg of the compound shown in Formula 49, with a yield of 79%.

[0112] The compound shown in Formula 49: 1 H NMR (500 MHz, CDCl3): δ 7.18 (t, J = 7.9 Hz, 2H), 6.75 (t, J = 7.3 Hz, 1H), 6.62 (d,J = 7.9 Hz, 2H), 4.31 (s, br., 2H), 4.12(q, J = 6.0 Hz, 1H), 3.86 (d, J = 6.1 Hz, 1H), 2.31 (s, br., 1H), 2.16 (s, br., 1H), 1.79 – 1.63 (m, 1H), 1.65 – 1.57 (m, 3H), 1.49 (s, 9H). 35) LiBr (43.5 mg, 0.5 mmol) and Boc₂O (43.6 mg, 0.2 mmol) were added to a MeCN (50 mL) solution of the compound shown in Formula 2 (9.5 mg, 0.1 mmol) at 0 °C, and the reaction mixture was stirred at 25 °C for 12 hours under an argon atmosphere. Then, PPh₃ (2.62 mg, 0.01 mmol) and AgF (12.7 mg, 0.1 mmol) were added at 25 °C, and the mixture was stirred at 25 °C for another 6 hours. The steps after the reaction were completed were the same as in step 1). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 16.6 mg of the compound shown in Formula 50, in 77% yield.

[0113] The compound shown in Formula 50: 1 H NMR (500 MHz, CDCl3): δ 5.03 (dt, J = 60.0, 5.8 Hz,1H), 4.26 (s, br., 2H), 2.19 (s, br., 2H), 1.82 – 1.69 (m, 3H), 1.61 – 1.53(m, 1H), 1.46 (s, 9H). 36) AgNO2 (258 mg, 2.0 mmol) was added to a DMF (5.0 mL) solution of the compound of Formula 23 (276 mg, 1.0 mmol) at 0 °C. The mixture was stirred at 25 °C for 6 hours under an argon atmosphere, protected from light. After the reaction was complete, the reaction mixture was concentrated under vacuum. The crude product was dissolved in ethanol (5.0 mL), and then 1 M NaOH (2.0 mL) was added at 25 °C. The reaction mixture was stirred at 25 °C for 3 hours under an argon atmosphere. The steps after the reaction were the same as in step 1). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 3:1) to give 115.0 mg of the compound of Formula 51, with a yield of 54%.

[0114] The compound shown in Formula 51:1 H NMR (400 MHz, CDCl3): δ 4.44 (q, J = 5.2 Hz, 1H), 4.13 (s, br., 2H), 2.67 (d, J = 4.9 Hz, 1H), 2.12 (s, br., 2H), 1.85 – 1.61(m, 3H), 1.54 – 1.47 (m, 1H), 1.46 (s, 9H). 37) AgNO2 (258 mg, 2.0 mmol) was added to a 5.0 mL Et2O solution of the compound of Formula 23 (276 mg, 1.0 mmol) at 0 °C. The mixture was stirred at 25 °C for 12 hours under an argon atmosphere, protected from light. The subsequent steps were the same as in step 1). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 75.0 mg of the compound of Formula 52, in 31% yield.

[0115] The compound shown in Formula 52: 1 H NMR (500 MHz, CDCl3): δ 4.90 (t, J = 6.1 Hz, 1H), 4.49 (dt, J = 6.4, 1.8 Hz, 2H), 2.33 (s, br., 2H), 2.00 – 1.91 (m, 2H), 1.69– 1.51 (m, 2H), 1.47 (s, 9H). 38) Add a mixture of the compound shown in Formula 23 (55.2 mg, 0.2 mmol), CsCO3 (65.2 mg, 0.2 mmol), Ir(dF(CF3)ppy)2(dtbpy)PF6 (2.24 mg, 2 μmol), and Ni(dtbpy)Br2 (2.45 mg, 5 μmol) to a 10 mL drying tube. Backfill the reaction tube three times with argon. Add 2.0 mL of trifluorotoluene (pre-purged with argon for 15 minutes to degas) to the mixture. Stir the mixture at 25 °C for 5 minutes, then place it in front of a KessilBlue LED photoreactor (450 nm, 100% light intensity) under fan cooling. Stir the mixture under argon for 2 hours. While stirring and irradiating the reaction mixture, a solution (1.0 mL, previously degassed by purging with argon for 15 min) of 4-bromotrifluorotoluene (22.5 mg, 0.1 mmol) and the compound of formula SI-40 (63.5 mg, 0.16 mmol) in trifluorotoluene was added via a syringe pump at a rate of 2.0 mL / h over 30 min. After complete addition, the mixture was irradiated for 90 min. After the reaction was complete, the reaction mixture was removed from the photoreactor and exposed to air. EA (2.0 mL) and methanol (60 µL) were added to the mixture. The reaction mixture was stirred at 25 °C for 1 h, then filtered through diatomaceous earth and washed with EA. The filtrate was concentrated under vacuum and subjected to rapid silica gel column chromatography (hexane:ethyl acetate, 10:1) to give 20.8 mg of the compound of formula 53 in 61% yield.

[0116] The compound shown in Formula 53: 1 H NMR (500 MHz, CDCl3): δ 7.63 – 7.52 (m, 4H), 4.18(q, J = 2.8 Hz, 1H), 4.04 (q, J = 3.2 Hz, 1H), 2.76 (s, 1H), 2.56 (ddt, J =13.3, 8.6, 4.1 Hz, 1H), 2.39 (ddt, J = 13.2, 8.7, 5.1 Hz, 1H), 1.99 (dtt, J =14.0, 8.8, 5.0 Hz, 1H), 1.87 (dddd, J = 19.0, 10.4, 5.1, 1.6 Hz, 2H), 1.77(dtd, J= 14.0, 8.9, 4.7 Hz, 1H), 1.47 (s, 9H). 39) The method is the same as in step 38), except that the compound shown in formula 22 (82.2 mg, 0.2 mmol) is used instead of the compound shown in formula 23. Using silica gel rapid column chromatography (hexane:ethyl acetate, 3:1), 19.0 mg (40%) of the compound shown in formula 54 was obtained.

[0117] The compound shown in Formula 54: 1 H NMR (500 MHz, CDCl3): δ 7.65 – 7.55 (m, 4H), 7.40 –7.31 (m, 5H), 5.20 (s, 2H), 4.36 – 4.03 (m, 4H), 3.61 (d, J = 11.5 Hz, 2H), 2.88 (s, 1H), 1.42 (s, 9H). 40) The method is the same as in step 38), except that Ni(dtbpy)Br2 (4.89 mg, 10 μmol) and 4-bromotoluene (17.1 mg, 0.1 mmol) are used. Using silica gel rapid column chromatography (hexane:ethyl acetate, 5:1), 14.9 mg of the compound shown in Formula 55 is obtained, with a yield of 52%.

[0118] The compound shown in Formula 55: 1 H NMR (500 MHz, CDCl3): δ 7.33 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 7.8 Hz, 2H), 4.17 (q, J = 3.4 Hz, 1H), 4.01 (q, J = 3.2 Hz, 1H), 2.68 (s, 1H), 2.59 – 2.49 (m, 1H), 2.41 – 2.34 (m, 4H), 1.97 (dtt, J = 14.1,9.1, 5.1 Hz, 1H), 1.90 – 1.79 (m, 2H), 1.74 (dtt, J = 13.8, 9.3, 4.9 Hz, 1H), 1.46 (s, 9H). 41) The method is the same as in step 38), except that 2-bromo-6-(trifluoromethyl)pyridine (22.6 mg, 0.1 mmol) is used instead of 4-bromotrifluorotoluene. Rapid silica gel column chromatography (hexane:ethyl acetate, 5:1) yielded 16.8 mg of the compound shown in Formula 56, in 49% yield.

[0119] The compound shown in Formula 56: 1 H NMR (500 MHz, CDCl3): δ 7.91 – 7.83 (m, 2H), 7.57(t, J = 3.4 Hz, 1H), 4.28 (s, 1H), 4.17 (s, 1H), 3.08 (s, 1H), 2.61 – 2.49(m, 1H), 2.38 (tt, J = 9.2, 4.3 Hz, 1H), 2.05 – 1.87 (m, 3H), 1.77 (qd, J =9.3, 4.6 Hz, 1H), 1.47 (s, 9H). 42) The method is the same as in step 40), except that N-tert-butoxycarbonyl-5-bromoindole (29.6 mg, 0.1 mmol) is used instead of 4-bromotrifluorotoluene. 23.5 mg of the compound shown in Formula 57 is obtained, with a yield of 57%.

[0120] The compound shown in Formula 57: 1 H NMR (500 MHz, CDCl3): δ 8.07 (d, J = 8.5 Hz, 1H), 7.67 (d, J = 1.8 Hz, 1H), 7.58 (d, J = 5.3 Hz, 1H), 7.36 (dd, J = 8.6, 1.8Hz, 1H), 6.55 (d, J = 3.7 Hz, 1H), 4.23 (td, J = 3.5, 1.7 Hz, 1H), 4.05 (td, J = 3.4, 1.6 Hz, 1H), 2.81 (s, 1H), 2.61 – 2.52 (m, 1H), 2.44 – 2.34 (m, 1H), 1.99 (ddt, J= 13.8, 10.0, 4.3 Hz, 1H), 1.93 – 1.83 (m, 2H), 1.77 (ddt, J =18.4, 9.1, 4.7 Hz, 1H), 1.67 (s, 9H), 1.48 (s, 9H). 43) Add a mixture of 5-chloromethyl-2-oxazolinone (13.6 mg, 0.1 mmol), CuTC (9.55 mg, 0.05 mmol), 4,4'-dimethoxy-2,2'-bipyridine (10.8 mg, 0.05 mol), 4-CzIPN (3.95 mg, 5 μmol), and MeCN (3.3 mL, 0.03 M) to a 10 mL tube. Add 1,5-diazabicyclo[4.3.0]non-5-ene (24.8 mg, 0.2 mmol) and water (45 μL, 2.5 mmol) to the mixture. Stir the resulting solution in air for 1–2 minutes to ensure complete bonding of the nucleophile with the copper precatalyst. Following this complexation period, the compound of formula 23 (55.2 mg, 0.2 mmol) and the compound of formula SI-41 (0.08 mL, 0.25 mmol) were added to the mixture, and the tube was then plugged with an 18G vent needle inserted into the plug. The reaction tube was placed in front of a Kessil Blue LED photoreactor (450 nm, 25% intensity) and cooled with a fan. The mixture was stirred in air for 12 hours. After 12 hours, methanol (0.1 mL) was added. The resulting solution was stirred in air for 2 hours, then filtered through diatomaceous earth and washed with EA. The filtrate was concentrated under vacuum and subjected to rapid silica gel column chromatography (hexane:ethyl acetate, 2:1) to give 18.2 mg of the compound of formula 58 in 55% yield.

[0121] The compound shown in Formula 58: 1 H NMR (500 MHz, CDCl3): δ 4.78 (dq, J = 10.7, 5.5 Hz,1H), 4.14 – 4.08 (m, 1H), 4.04 (s, 1H), 3.99 (q, J = 9.9 Hz, 1H), 3.78 – 3.67(m, 4H), 2.49 (dp, J = 14.7, 4.9, 4.5 Hz, 1H), 2.32 (dt, J= 13.2, 4.6 Hz,1H), 1.92 – 1.78 (m, 3H), 1.67 – 1.59 (m, 1H), 1.46 (s, 9H). 44) The method is the same as in step 43), except that the compound shown in formula 22 (82.2 mg, 0.2 mmol) is used instead of the compound shown in formula 23. Using silica gel rapid column chromatography (hexane:ethyl acetate, 1:1), 20.0 mg of the compound shown in formula 59 was obtained, with a yield of 43%.

[0122] The compound shown in Formula 59: 1 H NMR (400 MHz, CDCl3): δ 7.40 – 7.28 (m, 5H), 5.16(s, 2H), 4.82 (dq, J = 9.7, 5.0 Hz, 1H), 4.31 – 4.06 (m, 4H), 4.01 (t, J =9.1 Hz, 1H), 3.88 (d, J = 3.2 Hz, 1H), 3.78 (dd, J = 9.4, 5.7 Hz, 1H), 3.73(d, J = 5.0 Hz, 2H), 3.61 – 3.50 (m, 2H), 1.41 (s, 9H). 45) The method is the same as in step 43), except that 2-azacyclobutanone (7.1 mg, 0.1 mmol) is used instead of 5-chloromethyl-2-oxazolinone. The compound represented by Formula 60 was obtained in 14.9 mg by silica gel rapid column chromatography (hexane:ethyl acetate, 1:1), with a yield of 56%.

[0123] The compound shown in Formula 60: 1 H NMR (400 MHz, CDCl3): δ 4.09 (s, 1H), 4.05 (s, 1H), 3.64 (s, 1H), 3.47 (q, J = 4.4 Hz, 2H), 2.94 (t, J = 4.1 Hz, 2H), 2.43 (tt, J = 9.3, 4.2 Hz, 1H), 2.31 – 2.22 (m, 1H), 1.88 – 1.70 (m, 3H), 1.69 – 1.53 (m,1H), 1.45 (s, 9H). 46) Add a mixture of p-toluenesulfonamide (17.1 mg, 0.1 mmol), Ir[dF(CF3)ppy]2[4,4'-d(CF3)bpy]PF6 (0.9 mg, 0.8 μmol), and MeCN (1.0 mL) to a 10 mL tube. Add 1,5-diazabicyclo[4.3.0]non-5-ene (12.4 mg, 0.1 mmol) to the tube. Stir the resulting solution for 5 minutes, then add LiOt-Bu (24 mg, 0.3 mmol) and H2O (18 μL, 0.1 mmol) to the tube. Sonicate the suspension in air for 1 minute until the mixture becomes homogeneous. Then add Cu(TMHD)2 (12.9 mg, 0.03 mmol) to the tube and stir the solution in air for 1–2 minutes to ensure complete bonding of the nucleophile with the copper precatalyst. Following this complexation period, the compound of formula 23 (69 mg, 0.25 mmol) and the compound of formula SI-92 (99 mg, 0.25 mmol) were added to the mixture. The reaction tube was plugged, and an 18G vent needle was inserted into the plug. The tube was placed in front of a Kessil Blue LED photoreactor (450 nm, 25% light intensity) and cooled with a fan. The mixture was stirred in air for 4 hours. After 4 hours, EA (2.0 mL) was added to the mixture. The resulting solution was stirred in air for 2 hours, then filtered through diatomaceous earth and washed with EA. The filtrate was concentrated under vacuum and subjected to rapid silica gel column chromatography (hexane:ethyl acetate, 3:1) to give 12.8 mg of the compound of formula 61 in 35% yield.

[0124] The compound shown in Formula 61: 1 H (400 MHz, CDCl3): δ 7.74 (d, J = 8.2 Hz, 2H), 7.31(d, J = 8.1 Hz, 2H), 5.27 (d, J = 9.9 Hz, 1H), 3.73 (s, br., 1H), 3.53 (s, br., 1H), 3.27 (d, J = 9.9 Hz, 1H), 2.43 (s, 3H), 2.27 (s, br., 1H), 2.22 (s,br., 1H), 1.81 – 1.74 (m, 1H), 1.61 – 1.51 (m, 3H), 1.42 (s, 9H). 47) The method is the same as in step 43), except that 3-chloro-1H-pyrazole (10.2 mg, 0.1 mmol), 1H-indazole (11.8 mg, 0.1 mmol), and 4-chloropyrrolopyrimidine (15.3 mg, 0.1 mmol) are used instead of 5-chloromethyl-2-oxazolinone. Using silica gel rapid column chromatography (hexane:ethyl acetate, 5:1), 10.4 mg of the corresponding compound of formula 62 was obtained in 35% yield; or 14.7 mg of the compound of formula 63 in 47% yield. Using silica gel rapid column chromatography (hexane:ethyl acetate, 3:1), 15.0 mg of the corresponding compound of formula 65 was obtained in 43% yield.

[0125] The compound shown in Formula 62: 1 H NMR (500 MHz, CDCl3): δ 7.75 (s, 1H), 6.24 (s, 1H), 4.33 (s, 1H), 4.22 (s, 1H), 4.17 (s, 1H), 2.61 – 2.55 (m, 1H), 2.42 – 2.38(m, 1H), 1.97 – 1.84 (m, 3H), 1.79 – 1.66 (m, 1H), 1.46 (s, 9H). The compound shown in Formula 63: 1 H NMR (500 MHz, CDCl3): δ 8.05 (s, 1H), 7.76 (d, J =8.1 Hz, 1H), 7.38 (d, J = 3.6 Hz, 2H), 7.18 (dt, J = 7.9, 3.8 Hz, 1H), 4.78 –4.72 (m, 2H), 4.33 (s, 1H), 2.72 – 2.65 (m, 1H), 2.57 – 2.50 (m, 1H), 2.06 –1.95 (m, 3H), 1.88 – 1.81 (m, 1H), 1.45 (s, 9H). The compound shown in Formula 65: 1 H NMR (400 MHz, CDCl3): δ 8.62 (d, J= 2.1 Hz, 1H),7.85 (s, 1H), 6.67 (s, 1H), 4.73 (s, 1H), 4.33 (s, 1H), 4.19 (s, 1H), 2.67(s, br., 1H), 2.48 (s, br., 1H), 2.10 – 1.99 (m, 3H), 1.82 – 1.73 (m, 1H), 1.50 (s, 9H). 48) The method is the same as in step 43), except that 1H-indazole (11.8 mg, 0.1 mmol) is used instead of 5-chloromethyl-2-oxazolinone, and the compound shown in Formula 22 (82.2 mg, 0.2 mmol) is used instead of the compound shown in Formula 23. Using silica gel rapid column chromatography (hexane:ethyl acetate, 3:1), 15.2 mg of the compound shown in Formula 64 was obtained, with a yield of 34%.

[0126] The compound shown in Formula 64: 1 H NMR (500 MHz, CDCl3): δ 8.08 (s, 1H), 7.78 (d, J =8.1 Hz, 1H), 7.42 – 7.30 (m, 7H), 7.21 (t, J = 7.5 Hz, 1H), 5.21 (s, 2H), 4.81 (q, J = 3.6 Hz, 2H), 4.51 – 4.36 (m, 2H), 4.30 – 4.20 (m, 1H), 3.79 –3.70 (m, 2H), 1.40 (s, 9H). 49) The method is the same as in step 46), except that aniline (9.3 mg, 0.1 mmol) is used instead of p-toluenesulfonamide. Using silica gel rapid column chromatography (hexane:diethyl ether, 1:1), 10.9 mg of the compound shown in Formula 66 was obtained, with a yield of 38%.

[0127] The compound shown in Formula 66: 1 H NMR (500 MHz, CDCl3): δ 7.19 (t, J = 7.9 Hz, 2H), 6.75 (t, J = 7.3 Hz, 1H), 6.54 (d, J = 7.4 Hz, 2H), 4.35 (d, J= 7.0 Hz, 1H), 3.99 (s, br., 1H), 3.93 (s, br., 1H), 3.31 (d, J = 6.9 Hz, 1H), 2.54 – 2.46(m, 1H), 2.40 – 2.31 (m, 1H), 1.95 – 1.77 (m, 3H), 1.73 – 1.64 (m, 1H), 1.45(s, 9H). Example 9 Preparation of compounds SI-47, SI-76 to SI-89 ; 1) Add 20% Pd / C to a MeOH (10 mL) solution of the compound shown in Formula 10 (196 mg, 1.0 mmol), and backfill the reaction vessel three times with hydrogen. Stir the reaction solution for 12 hours at 25 °C under a hydrogen atmosphere. Filter the reaction solution through diatomaceous earth and concentrate under vacuum. The crude product is directly used for further reaction. Dissolve the crude product from the previous step in DCM (5.0 mL). Add DIPEA (193.5 mg, 1.5 mmol) and CbzCl (170 mg, 1.0 mmol) to the mixture at 0 °C. Stir the reaction mixture at 25 °C for 3 hours under an argon atmosphere. After the reaction is complete, concentrate the reaction mixture under vacuum. Dilute the residue with water and extract with DCM (3 × 5.0 mL). Wash the combined organic layers with brine and dry with Na2SO4. The solvent was removed under reduced pressure, and the crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 3:1) to give 229.1 mg of the compound shown in formula SI-47, with a yield of 69%.

[0128] The compound shown in formula SI-47: 1 H NMR (500 MHz, CDCl3): δ 7.38 – 7.26 (m, 5H), 5.13(d, J = 12.3 Hz, 1H), 5.06 (d, J = 12.3 Hz, 1H), 4.24 (s, 1H), 4.17 (s, 1H), 3.93 (s, br., 1H), 3.81 (s, br., 1H), 3.41 (d, J = 12.4 Hz, 1H), 3.39 – 3.34(m, 1H), 2.62 – 2.55 (m, 1H), 1.45 (s, 9H), 1.43 (d, J = 8.8 Hz, 1H). 2) Same as step 20) in Example 8, except that: the compound shown in Formula 3 (8.1 mg, 0.1 mmol) is used instead of the compound shown in Formula 1, aniline (32.2 mg, 0.2 mmol) is used instead of phenylpropanol, and K2CO3 (27.6 mg, 0.2 mmol) is used instead of DIPEA. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 20.0 mg of the compound shown in Formula SI-76, with a yield of 73%.

[0129] Compounds represented by formula SI-76: 1 H NMR (500 MHz, CDCl3): δ 7.18 (t, J = 7.8 Hz, 2H), 6.75 (t, J = 7.3 Hz, 1H), 6.61 (d, J = 8.0 Hz, 2H), 4.24 (d, J = 2.7 Hz, 2H), 3.55 (t, J = 2.9 Hz, 1H), 1.87 (d, J = 9.2 Hz, 2H), 1.71 (d, J = 8.6 Hz, 2H), 1.45 (s, 9H). 3) Same as step 15) in Example 8, except that the compound shown in Formula 2 (95 mg, 1 mmol), Boc2O (436 mg, 2 mmol), and TMSN3 (575 mg, 5 mmol) were used. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 5:1) to give 207.1 mg of the compound shown in Formula SI-77, with a yield of 87%.

[0130] Compounds represented by formula SI-77: 1 H NMR (500 MHz, CDCl3): δ 4.31 (t, J = 6.1 Hz, 1H), 4.22 (s, 2H), 2.17 (s, br., 2H), 1.80 – 1.68 (m, 3H), 1.57 – 1.47 (m, 1H), 1.46 (s, 9H). 4) Same as step 3) in Example 8, except that Ac2O (41.4 mg, 0.3 mmol) was used instead of TosCl. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:2) to give 10.0 mg of the compound shown in formula SI-78, in 51% yield.

[0131] Compounds represented by formula SI-78: 1 H NMR (500 MHz, CDCl3): δ 5.06 (t, J = 6.1 Hz, 1H), 4.55 (q, J = 4.6 Hz, 1H), 4.47 (q, J = 4.7 Hz, 1H), 2.30 – 2.21 (m, 1H), 2.12(s, 3H), 2.08 – 2.00 (m, 1H), 1.95 (s, 3H), 1.79 – 1.69 (m, 3H), 1.67 – 1.60(m, 1H). 5) At 0 °C, AgNO2 (258 mg, 2.0 mmol) was added to a 5.0 mL DMF solution of the compound shown in Formula 23 (276 mg, 1.0 mmol). The mixture was stirred at 25 °C for 6 hours under an argon atmosphere, protected from light. After the reaction was complete, the reaction mixture was concentrated under vacuum. The crude product was obtained by rapid silica gel column chromatography (hexane:ethyl acetate, 2:1), yielding 163.9 mg of the compound shown in Formula SI-79, in 68% yield.

[0132] Compounds represented by formula SI-79: 1 H NMR (500 MHz, CDCl3): δ 8.08 (s, 1H), 5.15 (t, J = 6.0 Hz, 1H), 4.32 (s, 2H), 2.22 (s, 2H), 1.76 – 1.56 (m, 4H), 1.47 (s, 9H). 6) Same as step 3) in Example 8, except that: the compound shown in Formula 2 (190 mg, 2 mmol) was used instead of TosCl, and TosBr (680 mg, 4 mmol) was used instead. 481.8 mg of the compound shown in Formula SI-80 was obtained, with a yield of 73%.

[0133] Compounds represented by formula SI-80: 1 H NMR (400 MHz, CDCl3): δ 7.79 (d, J= 8.4 Hz, 2H), 7.33 (d, J = 8.2 Hz, 2H), 4.72 (t, J = 6.3 Hz, 1H), 4.43 – 4.36 (m, 2H), 2.44(s, 3H), 2.24 – 2.12 (m, 2H), 2.12 – 2.00 (m, 2H), 1.92 – 1.80 (m, 2H). 7) Same as step 38) in Example 8, except that the compound shown in Formula 23 was replaced with the compound shown in Formula SI-80 (66 mg, 0.2 mmol). 8.7 mg of the compound shown in Formula SI-81 was obtained by silica gel rapid column chromatography (hexane:ethyl acetate, 5:1), in 35% yield.

[0134] Compounds represented by formula SI-81: 1 H NMR (500 MHz, CDCl3): δ 7.74 (d, J = 7.9 Hz, 1H), 7.31 (d, J = 7.9 Hz, 1H), 7.07 (s, 1H), 4.29 (s, 2H), 3.14 (s, 1H), 2.43 –2.32 (m, 5H), 2.27 – 2.09 (m, 2H), 2.12 – 1.88 (m, 2H). 8) Same as step 1) in Example 8, except that: the compound shown in Formula 10 (39.2 mg, 0.2 mmol) was used instead of TosCl, and CbzN3 (70.8 mg, 0.4 mmol) was used instead. 44.8 mg of the compound shown in Formula SI-82 was obtained, with a yield of 60%.

[0135] Compounds represented by formula SI-82: 1 H NMR (400 MHz, CDCl3): δ 7.36 – 7.25 (m, 5H), 5.17 – 5.04 (m, 2H), 4.41 – 4.34 (m, 2H), 4.29 (dt, J = 6.6, 3.6 Hz, 1H), 3.92 (d, J = 12.4 Hz, 2H), 3.32 (dd, J = 12.6, 5.3 Hz, 2H), 1.46 (s, 9H). 9) Same as step 37) in Example 8, except that the compound shown in Formula 23 was replaced with the compound shown in Formula 23 (441 mg, 1.0 mmol). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 5:1) to give 150.8 mg of the compound shown in Formula SI-83, in 40% yield.

[0136] Compounds represented by formula SI-83: 1 H NMR (500 MHz, CDCl3): δ 7.43 – 7.26 (m, 5H), 5.31(t, J = 5.6 Hz, 1H), 5.20 (d, J = 12.4 Hz, 1H), 5.13 (d, J = 12.3 Hz, 1H), 4.47 (dt, J = 6.3, 3.5 Hz, 1H), 4.41 (dt, J = 6.6, 3.6 Hz, 1H), 4.17 – 4.08(m, 2H), 3.31 (dd, J = 12.8, 10.1 Hz, 2H), 1.40 (s, 9H). 10) Same as step 5) in this embodiment, except that the compound shown in formula 22 (411 mg, 1.0 mmol) is used instead of the compound shown in formula 23. The crude product was obtained by silica gel rapid column chromatography (hexane:ethyl acetate, 3:1), yielding 282.0 mg of the compound shown in formula SI-84, with a yield of 75%.

[0137] Compounds represented by formula SI-84: 1 H NMR (500 MHz, CDCl3): δ 8.04 (s, 1H), 7.39 – 7.29 (m, 5H), 5.23 (t, J = 5.8 Hz, 1H), 5.22 – 5.10 (m, 2H), 4.39 (s, 1H), 4.34(s, 1H), 4.23 – 4.04 (m, 2H), 3.32 (d, J = 8.3 Hz, 1H), 3.29 (d, J = 8.5 Hz, 1H), 1.40 (s, 9H). 11) At 0 °C, Et3N (30.3 mg, 0.3 mmol) and acetyl chloride (11.7 mg, 0.15 mmol) were added to a DCM (1.0 mL) solution of the compound of formula SI-70 (34.8 mg, 0.1 mmol), and the reaction mixture was stirred at 25 °C for 3 hours under an argon atmosphere. The steps after the reaction were completed were the same as step 1) of this embodiment. 31.2 mg of the compound of formula SI-85 was obtained, with a yield of 80%.

[0138] Compounds represented by formula SI-85: 1 H NMR (500 MHz, CDCl3): δ 7.37 – 7.26 (m, 5H), 5.15(q, J = 12.5 Hz, 2H), 5.08 (t, J = 5.8 Hz, 1H), 4.33 (s, 1H), 4.28 (s, 1H), 4.18 – 4.03 (m, 2H), 3.26 (dd, J = 12.5, 4.6 Hz, 2H), 2.04 (s, 3H), 1.37 (s, 9H). 12) Same as step 7) in Example 8, except that the compound shown in Formula 10 (196 mg, 1 mmol) was used instead of the compound shown in Formula 1, and LiBr (434 mg, 5 mmol) and Boc2O (436 mg, 2 mmol) were used. 286.5 mg of the compound shown in Formula SI-86 was obtained, with a yield of 76%.

[0139] Compounds represented by formula SI-86: 1 H NMR (500 MHz, CDCl3): δ 4.63 (t, J = 5.8 Hz, 1H), 4.26 (s, 1H), 4.20 (dt, J = 6.4, 3.5 Hz, 1H), 4.05 (dd, J = 12.8, 3.5 Hz, 2H), 3.42 (dd, J = 12.7, 4.6 Hz, 2H), 1.46 (s, 9H), 1.44 (s, 9H). 13) Same as step 1) in Example 8, except that the compound shown in Formula 10 (392 mg, 2 mmol) was used, and TosBr (680 mg, 4 mmol) was used instead of TosCl. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 603.4 mg of the compound shown in Formula SI-87, with a yield of 70%.

[0140] Compounds represented by formula SI-87: 1 H NMR (500 MHz, CDCl3): δ 7.77 (d, J = 8.3 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 4.89 (t, J = 6.2 Hz, 1H), 4.49 – 4.41 (m, 2H), 3.81 – 3.65 (m, 4H), 2.44 (s, 3H), 1.46 (s, 9H). 14) At 25 °C, DIPEA (25.8 mg, 0.2 mmol), phenylacetylene (15.3 mg, 0.15 mmol), and CuI (19.0 mg, 0.1 mmol) were added to a THF (1.0 mL) solution of the compound of formula SI-60 (37.3 mg, 0.1 mmol). The subsequent steps were the same as in step 1) of this embodiment. 30.4 mg of the compound of formula SI-88 was obtained, with a yield of 64%.

[0141] Compounds represented by formula SI-88: 1 H NMR (500 MHz, CDCl3): δ 7.79 (d, J = 7.5 Hz, 2H),7.71 (s, 1H), 7.44 (t, J = 7.5 Hz, 2H), 7.36 (t, J = 7.3 Hz, 1H), 7.30 – 7.22(m, 5H), 5.19 (t, J = 5.9 Hz, 1H), 5.10 (d, J = 12.4 Hz, 1H), 5.02 (d, J =12.4 Hz, 1H), 4.70 (s, 2H), 4.16 (d, J = 12.4 Hz, 1H), 3.74 (d, J= 13.0 Hz, 1H), 3.60 (d, J = 13.3 Hz, 1H), 1.44 (s, 9H). 15) Cb2Cl (68 mg, 0.4 mmol) was added to a THF (1.0 mL) solution of the compound shown in Formula 2 (19 mg, 0.2 mmol) at 0 °C, and the reaction mixture was stirred at 25 °C for 12 hours under an argon atmosphere. The subsequent steps were the same as in step 1) of this embodiment. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 5:1) to obtain 40.4 mg of the compound shown in Formula SI-89, in 60% yield.

[0142] Compounds represented by formula SI-89: 1 H NMR (500 MHz, CDCl3): δ 7.38 – 7.29 (m, 5H), 5.13 (s, 2H), 4.28 (s, 2H), 4.06 (t, J = 5.8 Hz, 1H), 3.58 (t, J = 6.6 Hz, 2H), 3.44 (t, J = 6.2 Hz, 2H), 2.13 (s, br., 1H), 2.02 (s, br., 1H), 1.92 – 1.83(m, 2H), 1.78 – 1.66 (m, 5H), 1.52 – 1.41 (m, 1H). Example 10 Preparation of OXR antagonist (compound 67) This embodiment provides a method for preparing compound 67, the specific steps of which are as follows: ; 1) Same as step 13) in Example 8, except that: the compound shown in Formula 1 (230 mg, 1.0 mmol) was used instead of the compound shown in Formula 2, and LiAlH4 (76 mg, 2.0 mmol), Boc2O (436 mg, 2.0 mmol), and K2CO3 (276 mg, 2.0 mmol) were used. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 162.7 mg of the compound shown in Formula SI-38, with a yield of 49%.

[0143] The compound represented by formula SI-38: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 7.39 – 7.27(m, 5H), 5.16 (d,J = 1.8 Hz, 2H), 4.14 (s, 1H), 4.10 (s, 1H), 3.99 (s, br.,2H), 3.43 (dd, J = 12.3, 1.5 Hz, 2H), 2.61 – 2.53 (m, 1H), 1.40 (s, 9H), 1.37(d, J = 8.9 Hz, 1H). 13 C NMR (126 MHz, CDCl3): δ 156.61, 156.23, 136.65,128.50, 128.03, 127.85, 80.45, 67.06, 58.27, 45.69, 28.48, 28.28. HRMS ( m / z ):[M+Na] + calcd for C 18 H 24 N2NaO4 + 355.1634, found 355.1635. 2) 20% Pd(OH)₂ / C was added to a MeOH (4.0 mL) solution of the compound of formula SI-38 (132.8 mg, 0.4 mmol), and the reaction vessel was backfilled three times with hydrogen. The reaction solution was stirred for 12 hours at 25 °C under a hydrogen atmosphere. The reaction solution was filtered through diatomaceous earth and concentrated under vacuum. The crude product was dissolved in DMF (2.0 mL). DIPEA (103.2 mg, 0.8 mmol) and 2-chloro-4,6-dimethylpyrimidine (85.2 mg, 0.6 mmol) were added to the mixture. The reaction mixture was stirred at 120 °C for 6 hours under an argon atmosphere. The steps after the reaction were completed were the same as step 1) of this embodiment. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 3:1) to give 87.6 mg of the compound of formula SI-39, with a yield of 72%.

[0144] Compounds represented by formula SI-39: 1 H NMR (500 MHz, Methanol- d 4): δ 6.44 (s, 1H), 4.24– 4.16 (m, 4H), 3.55 (d, J = 12.3 Hz, 2H), 2.66 – 2.58 (m, 1H), 2.29 (s, 6H), 1.46 (d, J= 8.8 Hz, 1H), 1.33 (s, 9H). 3) Add CF3COOH (0.1 mL) to a DCM (1.0 mL) solution of the compound of formula SI-39 (60.8 mg, 0.2 mmol). Stir the reaction solution at 25 °C for 3 hours under an argon atmosphere. Concentrate the reaction solution under vacuum. Dissolve the crude product in DMF (1.0 mL). Add DIPEA (129.0 mg, 1.0 mmol), 2-thienylbenzoic acid (44.9 mg, 0.22 mmol), and HATU (83.6 mg, 0.22 mmol) to the mixture. Stir the reaction mixture at 25 °C for 12 hours under an argon atmosphere. The steps after the reaction are completed are the same as step 1) of this embodiment. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:1) to give 42.9 mg of the compound of formula 67, in 55% yield.

[0145] The compound shown in Formula 67: 1 H NMR (500 MHz, Methanol- d 4): δ 7.57 (dd, J = 7.6, 1.1Hz, 1H), 7.49 (td, J = 7.4, 1.9 Hz, 1H), 7.44 – 7.35 (m, 2H), 7.21 (dd, J =5.1, 1.2 Hz, 1H), 7.18 (dd, J = 3.6, 1.2 Hz, 1H), 6.78 (dd, J = 5.1, 3.6 Hz,1H), 6.46 (s, 1H), 4.63 (ddt, J = 6.2, 4.1, 2.1 Hz, 1H), 4.09 – 4.05 (m, 2H), 3.81 (dd, J = 12.6, 1.9 Hz, 1H), 3.57 (dd, J = 12.6, 1.7 Hz, 1H), 3.30 – 3.28(m, 1H), 2.51 (q, J = 6.9 Hz, 1H), 2.27 (s, 6H), 1.55 (d, J = 8.8 Hz, 1H). Example 11 Preparation of OXR antagonist (compound 68) ; This embodiment provides a method for preparing compound 68, the specific steps of which are as follows: 1) Same as step 3) in Example 10, except that: the compound shown in formula SI-39 (121.6 mg, 0.4 mmol), CF3COOH (0.2 mL), DIPEA (258.0 mg, 2.0 mmol), and HATU (167.2 mg, 0.44 mmol) were used, and 2-bromobenzoic acid (88.4 mg, 0.44 mmol) was used instead of 2-thienylbenzoic acid. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 2:1) to give 109.9 mg of the compound shown in formula SI-42, with a yield of 71%.

[0146] The compound shown in formula SI-42 is a white solid with a mp value of 118-119 °C. 1 H NMR (500 MHz, Methanol- d 4): δ 7.70 – 7.63 (m, 1H), 7.45 (ddd, J = 7.9, 6.9, 1.2 Hz, 1H),7.43 – 7.32 (m, 2H), 6.48 (s, 1H), 4.74 (ddt, J = 6.1, 4.0, 2.1 Hz, 1H), 4.29(ddt, J = 6.3, 3.9, 2.0 Hz, 1H), 4.23 (ddd, J = 12.6, 2.4, 1.1 Hz, 1H), 3.93(dd, J = 12.6, 1.9 Hz, 1H), 3.76 (dd, J = 12.8, 1.7 Hz, 1H), 3.64 (ddd, J =12.8, 2.6, 1.2 Hz, 1H), 2.91 (dtt, J = 9.0, 6.6, 1.2 Hz, 1H), 2.30 (s, 6H), 1.72 (d, J = 8.9 Hz, 1H). 13 C NMR (126 MHz, Methanol- d4): δ 168.57, 167.21,161.64, 136.00, 133.13, 131.22, 128.36, 127.66, 118.87, 109.22, 61.59, 58.42,48.94, 37.48, 29.44, 22.47. HRMS ( m / z ): [M+H] + calcd for C 18 H 20 BrN4O + 387.0820, found 387.0820. 2) To a solution of the compound of formula SI-42 (38.7 mg, 0.1 mmol) in 1,4-dioxane (1.0 mL) and H2O (0.1 mL), K2CO3 (34.5 mg, 0.25 mmol), cyclopropylboronic acid (12.9 mg, 0.15 mmol), and Pd(dppf)Cl2 (3.7 mg, 0.005 mmol) were added. The reaction solution was backfilled three times with argon gas and stirred for 12 hours at 100 °C under an argon atmosphere. The steps after the reaction were completed were the same as step 1) of this embodiment. 26.1 mg of the compound of formula 68 was obtained, with a yield of 75%.

[0147] The compound shown in Formula 68: 1 H NMR (500 MHz, Methanol- d 4): δ 7.35 (td, J = 7.6, 1.5Hz, 1H), 7.26 (dd, J = 7.6, 1.5 Hz, 1H), 7.20 (td, J = 7.5, 1.1 Hz, 1H), 6.92(dd, J = 7.9, 1.1 Hz, 1H), 6.48 (s, 1H), 4.71 (ddt, J = 6.2, 4.1, 2.1 Hz,1H), 4.36 – 4.27 (m, 2H), 3.83 (dd, J = 12.6, 1.7 Hz, 1H), 3.64 (dd, J =12.7, 1.7 Hz, 1H), 3.61 (dd, J = 13.1, 2.0 Hz, 1H), 2.88 (dtt, J= 8.8, 6.5,1.2 Hz, 1H), 2.29 (s, 6H), 1.97 (tt, J = 8.2, 5.5 Hz, 1H), 1.66 (d, J = 8.9Hz, 1H), 0.88 (dtt, J = 8.9, 6.4, 4.2 Hz, 1H), 0.71 (ddt, J = 8.5, 7.0, 4.8Hz, 1H), 0.54 – 0.46 (m, 2H). Example 12 Preparation of OXR antagonist (compound 69) ; This embodiment provides a method for preparing compound 68, the specific steps of which are as follows: To a 1.0 mL toluene solution of the compound of formula SI-42 (38.7 mg, 0.1 mmol), K3PO4 (53.8 mg, 0.25 mmol), pyrazole (10.2 mg, 0.15 mmol), CuI (1.9 mg, 0.01 mmol), and N,N'-dimethyl-1,2-cyclohexanediamine (2.84 mg, 0.02 mmol) were added. The reaction solution was backfilled three times with argon gas and stirred at 120 °C for 12 hours under an argon atmosphere. The procedure after the reaction was completed was the same as step 1) in Example 11. The crude product was subjected to rapid silica gel column chromatography (hexane:ethyl acetate, 1:3) to give 23.9 mg of the compound of formula 69, in 64% yield.

[0148] The compound shown in Formula 69: 1 H NMR (500 MHz, Methanol- d 4): δ 7.91 (d, J = 2.3 Hz,1H), 7.66 – 7.57 (m, 2H), 7.55 – 7.44 (m, 2H), 7.22 (d, J = 1.8 Hz, 1H), 6.51– 6.46 (m, 1H), 6.31 (t, J = 2.2 Hz, 1H), 4.62 (ddt, J = 6.2, 4.1, 2.1 Hz,1H), 4.22 (ddt, J = 6.2, 4.1, 2.1 Hz, 1H), 4.17 – 4.11 (m, 1H), 3.86 (dd,J =12.5, 2.0 Hz, 1H), 3.68 (d, J = 1.8 Hz, 0.3H), 3.65 (d, J = 1.8 Hz, 0.7H), 3.58 (dd, J = 12.6, 1.3 Hz, 1H), 2.75 – 2.65 (m, 1H), 2.29 (s, 6H), 1.64 (d, J = 8.7 Hz, 1H). Example 13 Preparation of OXR antagonist (compound SI-44) ; This embodiment provides a method for preparing compound SI-44, the specific steps of which are as follows: 1) Same as step 2) in Example 10, except that: K2CO3 (66.2 mg, 0.48 mmol) and 2-chlorobenzoxazole (61.2 mg, 0.4 mmol) were added to the mixture, and the reaction mixture was stirred at 90 °C for 16 hours under an argon atmosphere. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 2:1) to give 95.8 mg of the compound shown in formula SI-43, in 76% yield.

[0149] The compound shown in formula SI-43: 1 H NMR (500 MHz, CDCl3): δ 7.36 (d, J = 7.9 Hz, 1H), 7.26 (d, J = 7.9 Hz, 1H), 7.15 (td, J = 7.7, 1.2 Hz, 1H), 7.00 (td, J = 7.7,1.3 Hz, 1H), 4.34 – 4.01 (m, 4H), 3.65 (d, J = 11.4 Hz, 2H), 2.67 (q, J = 7.2Hz, 1H), 1.50 (d, J = 9.0 Hz, 1H), 1.37 (s, 9H). 2) Same as step 3) in Example 10, except that the compound shown in formula SI-39 was replaced with the compound shown in formula SI-43 (63 mg, 0.2 mmol). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:2) to give 50.5 mg of the compound shown in formula SI-44, in 63% yield.

[0150] The compound shown in formula SI-44 is a white solid with an mp value of 161-162 °C. 1 H NMR (500 MHz, Methanol- d 4): δ 7.59 (dt, J = 7.7, 0.9 Hz, 1H), 7.52 (ddd, J = 7.9, 5.8, 3.0Hz, 1H), 7.47 – 7.40 (m, 2H), 7.32 (t, J = 8.1 Hz, 2H), 7.24 (dd, J = 3.6, 1.2 Hz, 1H), 7.21 (td, J = 7.6, 1.1 Hz, 1H), 7.09 (td, J = 7.7, 1.3 Hz, 1H), 7.00 (d, J = 5.1 Hz, 1H), 6.71 (dd, J = 5.1, 3.6 Hz, 1H), 4.68 (ddt, J = 5.9,3.8, 2.0 Hz, 1H), 4.16 (dd, J = 11.5, 1.4 Hz, 1H), 4.15 – 4.09 (m, 1H), 3.81(dd, J = 11.4, 1.8 Hz, 1H), 3.56 (dd, J = 11.6, 1.6 Hz, 1H), 3.33 – 3.29 (m,1H), 2.65 (q, J = 7.2 Hz, 1H), 1.67 (d, J = 9.2 Hz, 1H). 13 C NMR (126 MHz, Methanol-) d4): δ 170.00, 161.81, 148.60, 142.06, 140.50, 132.83, 131.59,130.14, 129.79, 127.78, 127.55, 127.06, 126.57, 126.03, 123.99, 120.79,115.35, 108.68, 60.59, 57.32, 29.21. HRMS ( m / z ): [M+H] + calcd for C 23 H 20 N3O2S + 402.1276 was found to be 402.1277. Example 14 Preparation of OXR antagonist (compound SI-46) ; This embodiment provides a method for preparing compound SI-46, the specific steps of which are as follows: 1) Same as step 2) in Example 10, except that: the compound shown in formula SI-39 was replaced with the compound shown in formula SI-43 (126 mg, 0.4 mmol), 2-bromobenzoic acid (88.4 mg, 0.44 mmol) was replaced with 2-thienylbenzoic acid, and CF3COOH (0.2 mL), DIPEA (258.0 mg, 2.0 mmol), and HATU (167.2 mg, 0.44 mmol) were used. 105.1 mg of the compound shown in formula SI-45 was obtained, with a yield of 66%.

[0151] 2) The procedure was the same as in Example 12, except that the compound shown in formula SI-42 was replaced with the compound shown in formula SI-45 (39.8 mg, 0.1 mmol). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:4) to give 25.8 mg of the compound shown in formula SI-46, in 67% yield.

[0152] The compound shown in formula SI-46 is a white solid with an mp value of 199–200 °C. 1 H NMR (500 MHz, CDCl3): δ7.78 (d, J = 2.4 Hz, 1H), 7.55 – 7.48 (m, 2H), 7.47 (d, J = 7.5 Hz, 1H), 7.43– 7.35 (m, 2H), 7.28 (d, J= 8.4 Hz, 2H), 7.17 (t, J = 7.6 Hz, 1H), 7.03 (t, J = 7.7 Hz, 1H), 6.26 (t, J = 2.1 Hz, 1H), 4.64 (tt, J = 5.7, 2.3 Hz, 1H), 4.32 (dd, J = 11.5, 2.1 Hz, 1H), 4.15 (tt, J = 5.8, 2.2 Hz, 1H), 3.83 (dd, J = 11.6, 2.0 Hz, 1H), 3.75 (dd, J = 11.6, 2.2 Hz, 1H), 3.62 (dd, J = 11.7, 1.8Hz, 1H), 2.68 (q, J = 7.0 Hz, 1H), 1.67 (d, J = 8.9 Hz, 1H). 13 C NMR (126 MHz, CDCl3): δ 168.28, 162.06, 148.83, 142.90, 141.05, 137.82, 130.91, 129.99,129.29, 128.48, 127.78, 124.57, 124.09, 120.65, 116.39, 108.87, 107.43,60.54, 57.19, 49.01, 47.53, 29.49. HRMS ( m / z ): [M+H] + calcd for C 22 H 20 N5O2 + 386.1617, found 386.1618. Example 15 Preparation of OXR antagonist (compound SI-49) ; This embodiment provides a method for preparing compound SI-49, the specific steps of which are as follows: 1) Same as step 2) in Example 10, except that the compound shown in formula SI-38 was replaced with the compound shown in formula SI-47 (132.8 mg, 0.4 mmol). 85.1 mg of the compound shown in formula SI-48 was obtained, with a yield of 70%.

[0153] The compound shown in formula SI-48 is a white solid with a mp value of 168-170 °C. 1 H NMR (500 MHz, CDCl3): δ6.37 (s, 1H), 4.49 (ddt, J = 5.8, 3.9, 2.0 Hz, 1H), 4.41 (ddt, J = 5.6, 3.5,2.0 Hz, 1H), 3.98 (ddt, J = 12.2, 2.3, 1.3 Hz, 2H), 3.38 (td, J = 12.5, 1.8Hz, 2H), 2.69 (dtt, J = 8.7, 6.2, 1.2 Hz, 1H), 2.29 (s, 6H), 1.55 (d, J = 8.5Hz, 1H), 1.39 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ 167.44, 162.22, 156.19,111.08, 79.43, 58.28, 58.08, 44.44, 43.87, 28.72, 28.44, 24.00. HRMS ( m / z ):[M+H] + calcd for C 16 H 25 N4O2 + 305.1978, found 305.1976. 2) Same as step 3) in Example 10, except that the compound shown in formula SI-39 was replaced with the compound shown in formula SI-48 (60.8 mg, 0.2 mmol). 46.0 mg of the compound shown in formula SI-49 was obtained, with a yield of 59%.

[0154] The compound represented by formula SI-49: a colorless oily substance. 1 H NMR (500 MHz, Methanol- d 4): δ 7.57 (t, J= 7.3 Hz, 1H), 7.53 – 7.47 (m, 0.4H), 7.50 – 7.42 (m, 1H), 7.41 (td, J =7.4, 1.3 Hz, 0.6H), 7.35 (td, J = 7.3, 1.4 Hz, 1H), 7.22 (dd, J = 3.7, 1.2Hz, 0.4H), 7.16 (dd, J = 5.2, 1.1 Hz, 0.6H), 7.13 (dd, J = 5.1, 3.6 Hz,0.4H), 6.91 (dd, J = 3.6, 1.2 Hz, 0.6H), 6.81 (dd, J = 7.6, 1.4 Hz, 0.4H),6.70 (dd, J = 5.2, 3.6 Hz, 0.6H), 6.64 (s, 0.4H), 6.56 (s, 0.6H), 4.51 (dq, J = 5.3, 2.3 Hz, 0.6H), 4.45 (dt, J = 6.5, 3.5 Hz, 0.4H), 4.33 – 4.25 (m, 1H),4.16 (dq, J = 7.4, 2.6 Hz, 0.4H), 4.04 (dt, J = 13.6, 1.8 Hz, 0.6H), 3.82(dd, J = 13.5, 1.9 Hz, 0.6H), 3.72 (dd, J = 11.8, 1.7 Hz, 0.4H), 3.54 (dt, J = 11.9, 1.5 Hz, 0.6H), 3.41 (dd, J = 13.4, 1.4 Hz, 0.4H), 3.20 (dd, J = 11.8,2.0 Hz, 0.6H), 2.88 (dd, J = 12.0, 1.5 Hz, 0.4H), 2.74 – 2.66 (m, 0.6H), 2.55(q, J= 7.1 Hz, 0.4H), 2.31 (s, 6H), 1.65 (d, J = 8.8 Hz, 0.6H), 0.92 (d, J =8.8 Hz, 0.4H). Note: Two isomers with a 2:3 ratio, attributed to rotational isomerization of amide, were observed. 13 C NMR (126 MHz, Methanol- d 4): δ173.53, 173.23, 168.18, 167.81, 162.28, 161.13, 140.65, 140.27, 134.71,134.37, 131.06, 130.65, 129.64, 129.51, 129.13, 128.96, 127.85, 127.73,127.70, 127.24, 126.88, 126.52, 126.41, 126.13, 125.19, 111.65, 111.21,58.00, 57.89, 57.61, 46.28, 46.14, 43.61, 43.46, 37.51, 28.47, 27.69, 22.42,22.34. HRMS ( m / z ): [M+H] + calcd for C 22 H 23 N4OS + 391.1593, found 391.1591. Example 16 Preparation of OXR antagonist (compound SI-51) ; This embodiment provides a method for preparing compound SI-51, the specific steps of which are as follows: 1) Same as step 1) in Example 13, except that the compound shown in formula SI-43 was replaced with the compound shown in formula SI-47 (132.8 mg, 0.4 mmol). 100.8 mg of the compound shown in formula SI-50 was obtained, with a yield of 80%.

[0155] The compound shown in formula SI-50 is a white solid with a mp value of 188-190 °C. 1 H NMR (400 MHz, CDCl3): δ7.42 (dd, J = 8.2, 1.1 Hz, 1H), 7.30 (dt, J= 8.0, 0.8 Hz, 1H), 7.20 (td, J =7.7, 1.1 Hz, 1H), 7.09 (td, J = 7.7, 1.3 Hz, 1H), 4.54 (ddt, J = 5.8, 3.8,2.0 Hz, 1H), 4.48 (ddt, J = 5.7, 3.7, 2.0 Hz, 1H), 4.06 (ddd, J = 12.7, 2.2,1.1 Hz, 1H), 3.97 (ddd, J = 12.8, 2.2, 1.2 Hz, 1H), 3.58 (dd, J = 12.8, 1.8Hz, 1H), 3.53 (dd, J = 12.7, 1.8 Hz, 1H), 2.93 – 2.85 (m, 1H), 1.69 (d, J =8.7 Hz, 1H), 1.40 (s, 9H). 13 C NMR (100 MHz, CDCl3): δ 160.49, 155.78, 149.11,142.29, 124.10, 121.64, 117.11, 109.25, 80.12, 60.33, 60.07, 45.00, 44.75,29.67, 28.37. HRMS ( m / z ): [M+H] + calcd for C 17 H 22 N3O3 + 316.1661, found 316.1663. 2) Same as step 3) in Example 10, except that the compound shown in formula SI-39 was replaced with the compound shown in formula SI-50 (63 mg, 0.2 mmol). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:2) to give 52.1 mg of the compound shown in formula SI-51, with a yield of 65%.

[0156] The compound shown in formula SI-51 is a white solid with a mp value of 172-173 °C. 1 H NMR (500 MHz, CDCl3): δ7.49 (dd, J= 16.1, 7.7 Hz, 1H), 7.39 (q, J = 8.9 Hz, 2H), 7.31 (dq, J =12.9, 7.2, 5.9 Hz, 2.5H), 7.23 (dt, J = 11.5, 7.8 Hz, 2H), 7.17 – 7.04 (m,2H), 6.89 (d, J = 3.8 Hz, 0.5H), 6.22 (d, J = 5.1 Hz, 0.5H), 6.19 – 6.11 (m,0.5H), 4.55 (dd, J = 6.1, 3.2 Hz, 0.5H), 4.49 (t, J = 4.9 Hz, 0.5H), 4.30(dd, J = 6.0, 3.2 Hz, 0.5H), 4.19 (d, J = 13.2 Hz, 1H), 4.07 (q, J = 14.2 Hz, 1H), 3.84 (d, J = 12.3 Hz, 0.5H), 3.76 – 3.70 (m, 0.5H), 3.56 (d, J = 12.3Hz, 0.5H), 3.23 (dd, J = 12.5, 2.1 Hz, 0.5H), 3.01 (dd, J = 12.5, 2.0 Hz,0.5H), 2.87 (q, J = 7.0 Hz, 0.5H), 2.64 (q, J = 7.0 Hz, 0.5H), 1.69 (d, J =8.8 Hz, 0.5H), 0.83 (d, J = 8.8 Hz, 0.5H). Note: Two isomers with a 1:1 ratio, attributed to rotational isomerization of amide, were observed. 13C NMR (126 MHz, CDCl3): δ 172.68, 172.60, 167.05, 166.93, 160.22, 159.59, 149.07,148.90, 142.23, 142.19, 141.07, 139.86, 135.24, 134.71, 131.26, 129.57,129.41, 128.37, 127.98, 127.79, 127.17, 127.07, 126.88, 126.46, 126.32,125.75, 125.63, 124.22, 124.04, HRMS( m / z ): [M+H] + calcd for C 23 H 20 N3O2S + 402.1276, found 402,1276. Example 17 Preparation of OXR antagonist (compound 70) ; This embodiment provides a method for preparing compound 70, the specific steps of which are as follows: 1) Same as step 43) in Example 8, except that 2-azolidinone (8.7 mg, 0.1 mmol) was used instead of 5-chloromethyl-2-oxazolinone, and the compound shown in Formula 22 (82.2 mg, 0.2 mmol) was used instead of the compound shown in Formula 23. 12.5 mg of the compound shown in Formula SI-52 was obtained by silica gel rapid column chromatography (hexane:ethyl acetate, 1:1), in a yield of 30%.

[0157] 2) Same as step 1) in Example 13, except that the compound of formula SI-38 was replaced with the compound of formula SI-52 (41.7 mg, 0.1 mmol), and K2CO3 (16.5 mg, 0.12 mmol) and 2-chlorobenzoxazole (15.3 mg, 0.1 mmol) were used. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:2) to give 15.6 mg of the compound of formula SI-53, in 40% yield.

[0158] The compound represented by formula SI-53: a colorless oily substance.1 H NMR (500 MHz, CDCl3): δ 6.35 (s, 1H), 4.42 (t, J = 7.9 Hz, 3H), 4.26 (s, 3H), 3.94 (m, 3H), 3.75 (d, J = 12.8 Hz, 2H), 2.31 (s, 6H), 1.34 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ 166.87, 161.35,158.28, 156.77, 109.86, 80.89, 62.44, 56.08, 43.08, 28.17, 24.05. Note: NCH and NCHCH 2 were not observed. HRMS ( m / z ): [M+H] + calcd for C 19 H 28 N5O4 + 390.2141, found 390.2143. 3) Same as step 3) in Example 10, except that: the compound shown in formula SI-53 (15.6 mg, 0.04 mmol) is used instead of the compound shown in formula SI-39, 2-bromobenzoic acid (9.0 mg, 0.044 mmol) is used instead of 2-thienylbenzoic acid, and CF3COOH (0.05 mL), DIPEA (25.8 mg, 0.2 mmol), and HATU (16.7 mg, 0.044 mmol) are used. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:5) to give 9.9 mg of the compound shown in formula 70, with a yield of 52%.

[0159] The compound shown in Formula 70 is a colorless oily substance. 1H NMR (500 MHz, CDCl3): δ 7.49 (d, J = 8.1Hz, 1H), 7.48 – 7.41 (m, 1H), 7.34 (td, J = 7.4, 1.5 Hz, 1H), 7.24 (dd, J =11.7, 4.1 Hz, 3H), 6.94 (dd, J = 5.1, 3.6 Hz, 1H), 6.39 (s, 1H), 4.57 (dt, J= 4.4, 2.1 Hz, 1H), 4.47 (dd, J = 12.7, 2.8 Hz, 1H), 4.27 (td, J = 8.8, 6.5Hz, 1H), 4.19 (td, J = 8.8, 6.9 Hz, 1H), 3.98 (t, J = 3.9 Hz, 1H), 3.91 –3.85 (m, 2H), 3.66 (d, J = 13.0 Hz, 1H), 3.55 (dd, J = 12.9, 2.9 Hz, 1H), 3.40 (td, J = 8.8, 6.8 Hz, 1H), 2.99 (q, J = 8.2 Hz, 1H), 2.30 (s, 6H). 13 CNMR (126 MHz, CDCl3): δ 172.10, 166.68, 158.00, 141.52, 133.70, 131.51,130.46, 130.27, 128.23, 127.76, 127.74, 127.29, 125.84, 110.07, 63.74, 62.43,60.83, 56.55, 48.25, 46.71, 42.03, 24.00. HRMS ( m / z ): [M+H] + calcd forC 25 H 26 N5O3S + 476.1756, found 476.1754. Example 18 Preparation of OXR antagonist (compound 71) ; This embodiment provides a method for preparing compound 71, the specific steps of which are as follows: 1) Same as step 1) in Example 17, except that 2-azacyclobutanone (7.1 mg, 0.1 mmol) was used instead of 2-azolidinone. 24.1 mg of the compound shown in formula SI-54 was obtained, in 60% yield.

[0160] The compound represented by formula SI-54 is a yellow oily substance. 1 H NMR (400 MHz, CDCl3): δ 7.35 – 7.27(m, 5H), 5.14 (s, 2H), 4.31 – 3.97 (m, 4H), 3.71 (s, 1H), 3.58 – 3.41 (m,4H), 2.98 (t, J = 4.2 Hz, 2H), 1.39 (s, 9H). 13 C NMR (101 MHz, CDCl3): δ167.72, 156.51, 156.10, 136.37, 128.53, 128.13, 127.92, 81.27, 67.32, 61.94,60.91, 53.10, 45.35, 44.17, 38.44, 36.57, 28.15. HRMS ( m / z ): [M+Na] + calcdfor C 21 H 27 N3NaO5 + 424.1848, found 424.1848. 2) Same as step 2) in Example 17, except that the compound of formula SI-52 was replaced with the compound of formula SI-54 (80.2 mg, 0.2 mmol), and K2CO3 (33.1 mg, 0.24 mmol) and 2-chlorobenzoxazole (30.6 mg, 0.2 mmol) were used. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:1) to give 44.8 mg of the compound of formula SI-55, in 60% yield.

[0161] The compound shown in formula SI-55 is a white solid with a mp value of 144-145 °C. 1 H NMR (500 MHz, CDCl3): δ6.32 (s, 1H), 4.37 (d, J = 12.9 Hz, 1H), 4.24 (s, 3H), 3.78 (s, 1H), 3.64 (d, J= 12.8 Hz, 2H), 3.52 (s, br., 2H), 2.97 (t, J = 4.2 Hz, 2H), 2.27 (s, 6H), 1.31 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ 167.77, 166.86, 161.38, 156.82,109.83, 80.76, 62.66, 61.48, 53.52, 45.75, 44.78, 38.45, 36.47, 28.13, 24.03.HRMS ( m / z ): [M+H] + calcd for C 19 H 28 N5O3 + 374.2192, found 374.2192. 3) Same as step 3) in Example 17, except that the compound shown in formula SI-53 was replaced by the compound shown in formula SI-55 (37.3 mg, 0.1 mmol), and CF3COOH (0.1 mL), DIPEA (64.5 mg, 0.5 mmol), 2-bromobenzoic acid (22.1 mg, 0.11 mmol), and HATU (41.8 mg, 0.11 mmol) were used. The crude product was subjected to silica gel rapid column chromatography (dichloromethane:methanol, 10:1) to give 17.9 mg, 39% of the compound shown in formula 71.

[0162] The compound shown in Formula 71 is a white solid with an mp value of 98-99 °C. 1 H NMR (500 MHz, CDCl3): δ 7.50(d, J = 7.7 Hz, 1H), 7.43 (td, J = 7.6, 1.5 Hz, 1H), 7.32 (t, J = 7.5 Hz, 1H), 7.28 (d, J = 1.4 Hz, 1H), 7.23 (d, J = 3.6 Hz, 1H), 7.15 (d, J = 5.1 Hz, 1H), 6.85 (dd, J = 5.1, 3.6 Hz, 1H), 6.38 (s, 1H), 4.62 (dt, J= 4.2, 2.1 Hz, 1H), 4.41 (dd, J = 12.8, 2.7 Hz, 1H), 4.06 (s, 1H), 3.81 (dd, J = 12.8, 1.7Hz, 1H), 3.76 (s, 1H), 3.61 – 3.53 (m, 1H), 3.48 (dd, J = 13.0, 2.9 Hz, 1H), 3.17 (td, J = 5.3, 2.8 Hz, 1H), 2.96 – 2.92 (m, 1H), 2.87 (tdd, J = 14.7,5.4, 2.8 Hz, 2H), 2.30 (s, 6H). 13 C NMR (126 MHz, CDCl3): δ 172.01, 167.55,141.16, 133.45, 131.68, 130.38, 130.21, 127.98, 127.84, 127.67, 127.13,125.83, 110.03, 63.80, 61.01, 54.30, 48.00, 46.41, 37.81, 36.67, 23.99. Note: C2 and C4 on pyrimidine were not observed. HRMS ( m / z ): [M+H] + calcd forC 25 H 26 N5O2S + 460.1807 was found. Example 19 Preparation of OXR antagonist (compound 72) ; This embodiment provides a method for preparing compound 72, the specific steps of which are as follows: 1) Same as step 38) in Example 8, except that: the compound shown in Formula 22 (82.2 mg, 0.2 mmol) was used instead of the compound shown in Formula 23, and 2-bromo-6-(trifluoromethyl)pyridine (22.6 mg, 0.1 mmol) was used instead of 4-bromotrifluorotoluene. Using silica gel rapid column chromatography (hexane:ethyl acetate, 3:1), 19.1 mg of the compound shown in Formula SI-56 was obtained, with a yield of 40%.

[0163] The compound represented by formula SI-56: a colorless oily substance. 1H NMR (500 MHz, CDCl3): δ 7.90 (t, J =7.8 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 7.7 Hz, 1H), 7.39 – 7.29(m, 5H), 5.19 (s, 2H), 4.43 – 4.26 (m, 3H), 4.18 – 4.06 (m, 1H), 3.66 (d, J =12.4 Hz, 2H), 3.14 (s, 1H), 1.40 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ 160.02,156.43, 147.82 (q, J = 34.6 Hz), 138.33, 136.54, 128.54, 128.37, 128.10,127.88, 123.72, 121.39 (q, J = 274.4 Hz) 119.01 (q, J = 3.2 Hz), 81.15,67.24, 62.61, 61.56, 47.77, 46.34, 45.11, 28.20. 19 F NMR (471 MHz, CDCl3): δ -68.01. HRMS ( m / z ): [M+Na] + calcd for C 24 H 26 F3N3NaO4 + 500.1773, found 500.1774. 2) Same as step 2) in Example 17, except that the compound of formula SI-52 was replaced with the compound of formula SI-56 (47.7 mg, 0.1 mmol), and K2CO3 (16.5 mg, 0.12 mmol) and 2-chlorobenzoxazole (15.3 mg, 0.1 mmol) were used. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 5:1) to give 26.9 mg of the compound of formula SI-57, in 60% yield.

[0164] The compound represented by formula SI-57: a colorless oil. 1H NMR (500 MHz, CDCl3): δ 7.94 – 7.85(m, 2H), 7.60 (dd, J = 7.1, 1.5 Hz, 1H), 6.35 (s, 1H), 4.50 – 4.25 (m, 4H), 3.86 (d, J = 12.7 Hz, 2H), 3.22 (s, 1H), 2.32 (s, 6H), 1.35 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ 166.85, 161.76, 160.84, 156.83, 147.71 (q, J = 34.5 Hz),138.18, 123.81, 121.47 (q, J = 273.9 Hz), 118.82 (q, J = 3.1 Hz), 109.64, 80.57, 63.43, 62.18, 48.38, 46.80, 45.79, 28.21, 24.09. 19 F NMR (471 MHz, CDCl3): δ -67.98. HRMS ( m / z ): [M+H] + calcd for C 22 H 27 F3N5O2 + 450.2117, found 450.2119. 3) Same as step 3) in Example 17, except that the compound of formula SI-53 was replaced with the compound of formula SI-57 (26.9 mg, 0.06 mmol), and the following were used: CF3COOH (0.1 mL), DIPEA (38.7 mg, 0.3 mmol), 2-bromobenzoic acid (13.5 mg, 0.066 mmol), and HATU (25.1 mg, 0.066 mmol). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:1) to give 17.3 mg of the compound of formula 72, with a yield of 54%.

[0165] The compound shown in Formula 72 is a white solid with a mp value of 87-88 °C. 1 H NMR (500 MHz, CDCl3): δ 7.80(t, J = 7.8 Hz, 1H), 7.59 (d,J = 7.7 Hz, 1H), 7.48 (d, J = 7.7 Hz, 1H), 7.41(td, J = 7.5, 1.7 Hz, 1H), 7.40 – 7.29 (m, 2H), 7.27 (d, J = 8.2 Hz, 1H),7.15 (d, J = 3.5 Hz, 1H), 7.00 (d, J = 5.0 Hz, 1H), 6.68 (dd, J = 5.1, 3.6Hz, 1H), 6.38 (s, 1H), 4.80 – 4.75 (m, 1H), 4.46 (dd, J = 12.7, 2.4 Hz, 1H),4.37 – 4.32 (m, 1H), 4.00 (dd, J = 12.7, 1.8 Hz, 1H), 3.74 (d, J = 12.7 Hz,1H), 3.55 (dd, J = 12.8, 2.7 Hz, 1H), 3.26 (s, 1H), 2.31 (d, J = 8.0 Hz, 6H). 13 C NMR (126 MHz, CDCl3): δ 171.22, 166.77, 161.51, 159.59, 147.77 (q, J =34.5 Hz), 140.98, 138.31, 133.58, 131.68, 130.11, 129.99, 128.17, 127.85,127.45, 126.87, 125.57, 124.01, 121.45 (q, J = 274.2 Hz), 118.84 (q, J = 2.8Hz), 109.76, 64.05, 62.03, 49.18, 48.67, 47.66, 24.06. 19 F NMR (471 MHz,CDCl3): δ -67.89. HRMS ( m / z ): [M+H] + calcd for C 28 H 25F3N5OS + 536.1732, found 536.1730. Example 20 Preparation of OXR antagonist (compound 73) ; This embodiment provides a method for preparing compound 73, the specific steps of which are as follows: 1) A mixture of the compound of formula 22 (41.1 mg, 0.1 mmol), Ir(dF(CF3)ppy)2(dtbpy)PF6 (1.12 mg, 1 μmol), Ni(dtbpy)Br2 (2.45 mg, 5 μmol), TBAB (80.5 mg, 0.25 mmol), the compound of formula SI-93 (39.6 mg, 0.15 mmol), and K3PO4 (42.4 mg, 0.2 mmol) was prepared in a 10 mL drying tube. The reaction tube was backfilled with argon three times. MeCN (2.0 mL, previously purged with argon for 15 min for degassing) was added to the mixture. Then methyl p-toluenesulfonate (37.2 mg, 0.2 mmol) was added to the mixture, and the tube was placed in front of a Kessil Blue LED photoreactor (450 nm, 100% intensity) under fan cooling. The mixture was stirred under argon for 12 h. After the reaction was complete, the reaction mixture was removed from the photoreactor and exposed to air. EA (2.0 mL) was added to the mixture, followed by filtration through diatomaceous earth and rinsing with EA. The filtrate was concentrated under vacuum and subjected to rapid silica gel column chromatography (hexane:ethyl acetate, 5:1) to give 10.4 mg of the compound represented by formula SI-58, in 30% yield.

[0166] The compound represented by formula SI-58 is a yellow oily substance. 1 H NMR (500 MHz, CDCl3): δ 7.39 – 7.29(m, 5H), 5.16 (s, 2H), 4.12 (dd, J = 24.4, 12.1 Hz, 1H), 3.95 (t, J = 14.1Hz, 1H), 3.83 – 3.60 (m, 2H), 3.41 (d, J = 11.9 Hz, 2H), 1.77 (q, J = 6.8 Hz,1H), 1.43 – 1.37 (m, 12H). 13C NMR (126 MHz, CDCl3): δ 136.69, 128.49, 127.97,127.77, 80.41, 67.02, 62.85, 62.01, 46.44, 45.30, 36.40, 28.28, 15.43. Note: NCO were not observed. HRMS ( m / z ): [M+Na] + calcd for C 19 H 26 N2NaO4 + 369.1790, found 369.1788. 2) Same as step 2) in Example 17, except that the compound shown in formula SI-52 was replaced with the compound shown in formula SI-58 (34.6 mg, 0.1 mmol). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 3:1) to give 13.0 mg of the compound shown in formula SI-59, with a yield of 41%.

[0167] The compound represented by formula SI-59: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 6.31 (s, 1H), 4.29 – 4.23 (m, 1H), 4.13 (d, J = 12.5 Hz, 1H), 3.86 (s, 1H), 3.80 (s, 1H), 3.62 – 3.56 (m, 2H), 2.29 (s, 6H), 1.84 (q, J = 6.7 Hz, 1H), 1.42 (d, J = 6.6Hz, 3H), 1.35 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ 166.74, 161.90, 157.58,109.29, 79.85, 63.69, 62.72, 47.08, 46.13, 36.92, 28.29, 24.10, 15.63. HRMS( m / z ): [M+H] + calcd for C 17 H 27 N4O2 + 319.2134, found 319.2137. 3) Same as step 3) in Example 17, except that the compound of formula SI-53 was replaced with the compound of formula SI-59 (13.0 mg, 0.04 mmol), and the following were used: CF3COOH (0.1 mL), DIPEA (26.5 mg, 0.21 mmol), 2-bromobenzoic acid (9.18 mg, 0.045 mmol), and HATU (17.1 mg, 0.045 mmol). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:1) to give 9.8 mg of the compound of formula 73, in 59% yield.

[0168] The compound shown in Formula 73 is a white solid with an mp of 61-62 °C. 1 H NMR (500 MHz, CDCl3): δ 7.49(d, J = 8.6 Hz, 1H), 7.43 – 7.39 (m, 1H), 7.38 – 7.29 (m, 2H), 7.29 – 7.25(m, 1H), 7.16 (dd, J = 5.1, 1.2 Hz, 1H), 6.88 (dd, J = 5.1, 3.6 Hz, 1H), 6.34(s, 1H), 4.23 (dd, J = 12.5, 2.4 Hz, 1H), 4.18 (dt, J = 4.1, 2.1 Hz, 1H), 3.77 (dd, J = 12.5, 1.8 Hz, 1H), 3.53 (d, J = 12.6 Hz, 1H), 3.49 (dt, J =4.1, 2.0 Hz, 1H), 3.35 (dd, J = 12.5, 2.5 Hz, 1H), 2.29 (d, J = 11.2 Hz, 6H), 1.88 (q, J = 6.6 Hz, 1H), 1.01 (d, J = 6.6 Hz, 3H). 13C NMR (126 MHz, CDCl3): δ 170.72, 166.69, 161.62, 141.08, 134.20, 131.73, 129.98, 129.74, 127.92,127.89, 127.70, 126.98, 125.69, 109.45, 65.14, 62.30, 49.28, 47.89, 37.25,24.05, 14.68. HRMS ( m / z ): [M+H] + calcd for C 23 H 25 N4OS + 405.1749, found 405.1751. Example 21 Preparation of OXR antagonist (compound 74) ; This embodiment provides a method for preparing compound 74, the specific steps of which are as follows: 1) Same as step 15) in Example 8, except that the compound shown in Formula 2 was replaced with the compound shown in Formula 1 (460 mg, 2 mmol), and Boc2O (872 mg, 4 mmol) and TMSN3 (1.15 g, 10 mmol) were used. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 4:1) to give 678.9 mg of the compound shown in Formula SI-60, with a yield of 91%.

[0169] The compound shown in formula SI-60 is a white solid with an mp value of 77-79 °C. 1 H NMR (400 MHz, CDCl3): δ7.38 – 7.24 (m, 5H), 5.22 – 5.08 (m, 2H), 4.36 (t, J = 5.9 Hz, 1H), 4.32 –4.17 (m, 2H), 4.03 (s, br., 2H), 3.36 (dd, J = 12.4, 5.6 Hz, 2H), 1.38 (s,9H). 13 C NMR (101 MHz, CDCl3): δ 156.09, 155.89, 136.59, 128.49, 128.02,127.84, 81.23, 67.13, 61.73, 61.31, 53.36, 40.90, 40.55, 28.10. HRMS ( m / z ):[M+Na] + calcd for C 18 H 23 N5NaO4 + 396.1648, found 396.1647. 2) Same as step 14) in Example 9, except that methyl propargylate (126 mg, 1.5 mmol) was used instead of phenylacetylene, and the compound shown in formula SI-60 (373 mg, 1.0 mmol), DIPEA (258 mg, 2.0 mmol), and CuI (190 mg, 1.0 mmol) were used. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 2:1) to give 329.0 mg of the compound shown in formula SI-61, with a yield of 72%.

[0170] The compound shown in formula SI-61 is a yellow solid with an mp value of 146-148 °C. 1 H NMR (500 MHz, CDCl3): δ8.08 (s, 1H), 7.35 – 7.27 (m, 3H), 7.26 – 7.23 (m, 2H), 5.18 (t, J = 5.9 Hz, 1H), 5.10 (d, J = 12.5 Hz, 1H), 5.00 (d, J = 12.4 Hz, 1H), 4.72 – 4.67 (m,2H), 4.13 (s, br., 1H), 4.11 (s, br., 1H), 3.94 (s, 3H), 3.65 (d, J = 13.1Hz, 1H), 3.49 (d, J = 13.3 Hz, 1H), 1.42 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ160.63, 155.51, 155.34, 140.30, 136.17, 128.52, 128.09, 127.73, 126.58,82.07, 67.37, 61.29, 52.39, 51.39, 40.63, 28.15. HRMS ( m / z ): [M+Na] + calcdfor C 22 H 27 N5NaO6 +480.1859, found 480.1859. 3) Same as step 1) in Example 13, except that the compound of formula SI-38 was replaced with the compound of formula SI-61 (91.4 mg, 0.2 mmol), and K2CO3 (33.1 mg, 0.24 mmol) and 2-chlorobenzoxazole (30.6 mg, 0.2 mmol) were used. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:1) to give 59.8 mg of the compound of formula SI-62, with a yield of 68%.

[0171] The compound represented by formula SI-62: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 8.13 (s, 1H),7.33 (d, J = 7.8 Hz, 1H), 7.25 (d, J = 7.8 Hz, 1H), 7.15 (td, J = 7.7, 1.1Hz, 1H), 7.03 (td, J = 7.8, 1.2 Hz, 1H), 5.29 (t, J = 5.9 Hz, 1H), 4.85 (d, J = 5.9 Hz, 2H), 4.37 (d, J = 12.6 Hz, 2H), 3.89 (s, 3H), 3.83 (d, J = 12.7 Hz, 2H), 1.42 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ 160.70, 160.53, 155.18, 148.84,142.39, 140.38, 126.59, 124.18, 121.09, 116.64, 109.12, 82.35, 52.37, 51.52,28.18. Note: NCH and NCHCH 2 were not observed. HRMS ( m / z ): [M+H] + calcd forC 21 H 25 N6O5 + 441.1886, found 441.1885. 4) Same as step 3) in Example 17, except that the compound shown in formula SI-53 was replaced with the compound shown in formula SI-62 (44.0 mg, 0.1 mmol), and CF3COOH (0.1 mL), DIPEA (64.5 mg, 0.5 mmol), 2-bromobenzoic acid (22.1 mg, 0.11 mmol), and HATU (41.8 mg, 0.11 mmol) were used. The crude product was subjected to silica gel rapid column chromatography (dichloromethane:methanol, 20:1) to obtain 24.7 mg (47%) of the compound shown in formula 74.

[0172] The compound shown in Formula 74 is a colorless oily substance. 1 H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 7.55 (dd, J = 7.8, 1.3 Hz, 1H), 7.49 (td, J = 7.4, 1.6 Hz, 1H), 7.45 (dd, J =7.6, 1.6 Hz, 1H), 7.39 (td, J = 7.3, 1.4 Hz, 1H), 7.29 (dd, J = 7.9, 1.2 Hz, 1H), 7.25 (d, J = 1.1 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H), 7.14 (td, J = 7.6,1.1 Hz, 1H), 7.10 – 7.04 (m, 1H), 7.01 (td, J = 7.7, 1.3 Hz, 1H), 6.83 (dd, J = 5.1, 3.6 Hz, 1H), 5.22 (s, 1H), 4.87 (t, J = 6.0 Hz, 1H), 4.55 (s, 1H), 4.32 (d, J = 11.5 Hz, 1H), 3.90 (d, J = 11.8 Hz, 1H), 3.82 (s, 3H), 3.67 (d, J = 12.6 Hz, 1H), 3.47 (d, J = 12.1 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ169.66, 160.47, 160.25, 148.76, 142.20, 140.41, 140.22, 132.67, 131.70,130.78, 130.31, 128.35, HRMS ( m / z ):[M+H] + calcd for C 27 H 23 N6O4S + 527.1501, found 527.1503. Example 22 Preparation of OXR antagonist (compound 75) ; This embodiment provides a method for preparing compound 75, the specific steps of which are as follows: 1) Same as step 31) in Example 8, except that: the compound shown in Formula 1 (230 mg, 1.0 mmol) was used instead of the compound shown in Formula 2, aniline (322 mg, 2.0 mmol) was used instead of benzylamine, and Boc2O (436 mg, 2.0 mmol) and K2CO3 (276 mg, 2.0 mmol) were used. 346.9 mg of the compound shown in Formula SI-63 was obtained, with a yield of 82%.

[0173] The compound shown in formula SI-63 is a yellow solid with a maximum temperature of 115-116 °C. 1 H NMR (500 MHz, CDCl3): δ7.37 – 7.28 (m, 5H), 7.22 – 7.15 (m, 2H), 6.78 (t, J = 7.3 Hz, 1H), 6.63 (d, J = 7.4 Hz, 2H), 5.22 – 5.11 (m, 2H), 4.37 (s, 1H), 4.32 (s, 1H), 4.26 (t, J = 5.7 Hz, 1H), 4.11 (s, br., 2H), 3.33 (t, J = 12.1 Hz, 2H), 1.42 (s, 9H).13 CNMR (126 MHz, CDCl3): δ 156.17, 156.16, 145.88, 136.44, 129.54, 128.54,128.11, 127.85, 119.01, 113.33, 80.95, 67.26, 47.81, 28.22. Note: NCH and NCHCH 2 were not observed. HRMS ( m / z ): [M+Na] + calcd for C 24 H 29 N3NaO4 + 446.2056, found 446.2057. 2) Same as step 1) in Example 13, except that the compound shown in formula SI-38 was replaced with the compound shown in formula SI-63 (87.4 mg, 0.2 mmol), and 2-chlorobenzoxazole (30.6 mg, 0.2 mmol) was used. 64.1 mg of the compound shown in formula SI-64 was obtained, with a yield of 79%.

[0174] The compound shown in formula SI-64 is a white solid with a mp value of 186-188 °C. 1 H NMR (500 MHz, CDCl3): δ7.39 (dd, J = 7.9, 1.2 Hz, 1H), 7.28 (dd, J = 8.1, 1.1 Hz, 1H), 7.18 (dtt, J = 7.6, 4.9, 2.7 Hz, 3H), 7.04 (td, J = 7.8, 1.3 Hz, 1H), 6.79 (tt, J = 7.4,1.1 Hz, 1H), 6.70 – 6.63 (m, 2H), 4.48 (d, J = 5.4 Hz, 2H), 4.42 – 4.26 (m,3H), 4.12 (dd, J = 7.1, 2.6 Hz, 1H), 3.61 (d, J = 12.2 Hz, 2H), 1.40 (s, 9H). 13C NMR (126 MHz, CDCl3): δ 161.56, 156.10, 148.90, 145.94, 142.76, 129.55,124.17, 120.89, 119.08, 116.43, 113.37, 109.04, 81.21, 48.13, 28.24. Note: NCH and NCHCH 2 were not observed. HRMS ( m / z ): [M+H] + calcd for C 23 H 27 N4O3 + 407.2083, found 407.2083. 3) Same as step 4) in Example 21, except that the compound shown in formula SI-53 was replaced with the compound shown in formula SI-64 (42.0 mg, 0.1 mmol). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:1) to give 27.1 mg of the compound shown in formula 75, in 55% yield.

[0175] The compound shown in Formula 75 is a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 7.55 (d, J = 7.7Hz, 1H), 7.50 – 7.36 (m, 4H), 7.31 (d, J = 3.6 Hz, 1H), 7.27 (s, 1H), 7.17(t, J = 7.5 Hz, 1H), 7.12 – 7.00 (m, 4H), 6.80 (s, 1H), 6.73 (d, J = 7.5 Hz, 1H), 6.53 (d, J = 7.9 Hz, 2H), 4.86 (s, 1H), 4.30 (dd, J = 12.1, 2.5 Hz, 1H), 4.03 (s, 2H), 3.78 (d, J = 12.0 Hz, 1H), 3.43 (s, 2H), 2.80 (s, 1H). 13C NMR(126 MHz, CDCl3): δ 169.28, 148.50, 145.46, 140.72, 133.45, 131.99, 131.47,130.25, 130.10, 129.43, 128.15, 127.71, 127.68, 127.10, 126.36, 124.46,121.28, 119.13, 116.13, 113.33, 109.13, 63.29, 59.97, 49.57, 44.83, 43.82. Note: C2 on the benzoxazole were not observed. HRMS ( m / z ): [M+H] + calcd forC 29 H 25 N4O2S + 493.1698, found 493.1697. Example 23 Preparation of OXR antagonist (compound 76) ; This embodiment provides a method for preparing compound 76, the specific steps of which are as follows: 1) PPh3 (262 mg, 1.0 mmol) was added to a MeCN (10 mL) solution of the compound of formula SI-60 (373 mg, 1.0 mmol) at 25 °C, and the mixture was stirred at 25 °C for 6 hours under an argon atmosphere. After the reaction was complete, the reaction mixture was concentrated under vacuum. The crude product was subjected to silica gel rapid column chromatography (dichloromethane:methanol, 20:1) to give 509.9 mg of the compound of formula SI-65, in 84% yield.

[0176] Compound represented by formula SI-65: colorless oil, HRMS ( m / z ): [M+H] + calcd for C 36 H 39 N3O4P + 608.2678, found 608.2680. 2) At 25 °C, 0.6 mL of H₂O was added to a THF (18 mL) solution of the compound of formula SI-65 (607.0 mg, 1.0 mmol). The mixture was stirred at 25 °C for 12 hours under an argon atmosphere. After the reaction was complete, the reaction mixture was concentrated under vacuum. The residue was diluted with water and extracted with EA (3 × 1.0 mL). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:3) to give 295.0 mg of the compound of formula SI-66, in 85% yield.

[0177] The compound represented by formula SI-66: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 7.37 – 7.24(m, 5H), 5.22 – 5.10 (m, 2H), 4.18 – 3.93 (m, 4H), 3.79 (t, J = 6.0 Hz, 1H), 3.37 (dd, J = 12.6, 8.7 Hz, 2H), 1.40 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ156.12, 136.50, 128.53, 128.08, 127.86, 80.61, 67.19, 62.57, 40.95, 47.13,28.23. Note: a NCO was not observed. HRMS ( m / z ): [M+Na] + calcd for C 18 H 25 N3NaO4 + 370.1743, found 370.1743. 3) Et3N (165 mg, 1.5 mmol) and acetyl chloride (58.9 mg, 0.75 mmol) were added to a DCM (3.0 mL) solution of the compound of formula SI-65 (303.5 mg, 0.5 mmol) at 0 °C, and the reaction mixture was stirred at 25 °C for 3 hours under an argon atmosphere. After the reaction was complete, the reaction mixture was concentrated under vacuum. The residue was diluted with water and extracted with DCM (3 × 3 mL). The combined organic layers were washed with brine and dried over Na2SO4. The solvent was removed under reduced pressure, and the crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 3:1) to give 173.1 mg of the compound of formula SI-67, in 89% yield.

[0178] The compound shown in formula SI-67 is a white solid with an mp value of 131-132 °C. 1 H NMR (500 MHz, CDCl3): δ7.38 – 7.28 (m, 5H), 5.92 (d, J = 8.4 Hz, 1H), 5.20 (d, J = 12.3 Hz, 1H), 5.11 (d, J = 12.4 Hz, 1H), 4.84 (q, J = 6.8 Hz, 1H), 4.29 – 4.20 (m, 2H), 4.09 (d, J = 46.8 Hz, 2H), 3.32 (dd, J = 13.0, 6.5 Hz, 2H), 1.97 (s, 3H), 1.40 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ 170.82, 156.25, 155.73, 136.20,128.61, 128.49, 128.29, 127.86, 81.08, 67.44, 43.26, 28.20, 23.24. Note: NCH and NCHCH 2 were not observed. HRMS ( m / z ): [M+Na] + calcd for C 20 H 27 N3NaO5 + 412.1848, found 412.1848. ; 4) Same as step 2) in Example 10, except that the compound of formula SI-38 was replaced with the compound of formula SI-67 (77.8 mg, 0.2 mmol), and DIPEA (51.6 mg, 0.4 mmol) and 2-chloro-4,6-dimethylpyrimidine (42.6 mg, 0.3 mmol) were used. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:2) to give 48.4 mg of the compound of formula SI-68, in 67% yield.

[0179] The compound represented by formula SI-68 is a yellow solid with an mp value of 191-192 °C. 1H NMR (500 MHz, CDCl3): δ6.42 (s, 1H), 5.75 (d, J = 9.3 Hz, 1H), 4.99 (dt, J = 9.4, 6.0 Hz, 1H), 4.42– 4.14 (m, 4H), 3.53 (d, J = 13.4 Hz, 2H), 2.34 (s, 6H), 1.95 (s, 3H), 1.37(s, 9H). 13 C NMR (126 MHz, CDCl3): δ 170.59, 167.06, 161.47, 155.79, 110.30,80.60, 43.68, 28.25, 24.08, 23.49. Note: NCH and NCHCH2 were not observed.HRMS ( m / z ): [M+H] + calcd for C 18 H 28 N5O3 + 362.2192, found 362,2192. 5) Same as step 4) in Example 21, except that the compound shown in formula SI-61 was replaced with the compound shown in formula SI-68 (36.1 mg, 0.1 mmol). 29.1 mg of the compound shown in formula 76 was obtained, with a yield of 65%.

[0180] The compound shown in Formula 76 is a colorless oily substance. 1 H NMR (500 MHz, Methanol- d 4): δ 7.59 (d, J = 7.7 Hz, 1H), 7.57 – 7.47 (m, 1H), 7.46 – 7.38 (m, 2H), 7.20 – 7.14 (m, 2H), 6.75 – 6.70 (m, 1H), 6.50 (s, 1H), 4.81 – 4.74 (m, 1H), 4.43 (t, J = 6.1 Hz,1H), 4.23 – 4.15 (m, 2H), 3.65 (dd, J = 13.2, 1.5 Hz, 1H), 3.39 (d, J= 2.2Hz, 2H), 2.30 (s, 6H), 1.88 (s, 3H). 13 C NMR (126 MHz, Methanol- d 4): δ 173.11,170.23, 167.03, 160.80, 140.34, 132.95, 131.69, 130.17, 129.74, 127.69,127.53, 127.03, 126.38, 125.91, 109.44, 63.91, 60.48, 45.63, 44.01, 42.94,22.50, 20.72. HRMS ( m / z ): [M+H] + calcd for C 24 H 26 N5O2S + 448.1807, found448.1808. Example 24 Preparation of OXR antagonist (compound 77) ; This embodiment provides a method for preparing compound 77, the specific steps of which are as follows: 1) Same as step 2) in Example 10, except that the compound of formula SI-38 was replaced with the compound of formula 34 (72.4 mg, 0.2 mmol), and DIPEA (51.6 mg, 0.4 mmol) and 2-chloro-4,6-dimethylpyrimidine (42.6 mg, 0.3 mmol) were used. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 2:1) to give 38.7 mg of the compound of formula SI-69, in 58% yield.

[0181] The compound represented by formula SI-69: a colorless oily substance. 1 H NMR (400 MHz, CDCl3): δ 6.27 (s, 1H), 4.33 (d, J = 15.2 Hz, 4H), 4.04 (t, J = 5.6 Hz, 1H), 3.37 (s, 1H), 3.34 (s, 1H), 3.33 (s, 3H), 2.27 (s, 6H), 1.30 (s, 9H). 13C NMR (101 MHz, CDCl3): δ166.59, 161.41, 157.05, 109.12, 80.24, 70.12, 62.00, 57.00, 40.93, 28.09,24.06. HRMS ( m / z ): [M+H] + calcd for C 17 H 27 N4O3 + 335.2083, found 335.2082. 2) Same as step 4) in Example 21, except that the compound shown in formula SI-62 was replaced with the compound shown in formula SI-69 (33.4 mg, 0.1 mmol). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:2) to give 25.2 mg of the compound shown in formula 77, in 60% yield.

[0182] The compound shown in Formula 77 is a colorless oily substance. 1 H NMR (500 MHz, Methanol- d 4): δ 7.58 (dd, J = 7.8, 1.3 Hz, 1H), 7.55 – 7.46 (m, 1H), 7.41 (td, J = 7.4, 1.3 Hz, 1H), 7.37(dd, J = 7.6, 1.6 Hz, 1H), 7.23 (dd, J = 5.2, 1.2 Hz, 1H), 7.17 (dd, J = 3.6, 1.2 Hz, 1H), 6.77 (dd, J = 5.1, 3.6 Hz, 1H), 6.45 (s, 1H), 4.80 – 4.72 (m,1H), 4.23 – 4.13 (m, 2H), 3.91 (t, J = 5.8 Hz, 1H), 3.51 (dd, J = 12.7, 1.1Hz, 1H), 3.46 (dd, J = 12.8, 3.6 Hz, 1H), 3.31 – 3.26 (m, 4H), 2.28 (d, J =16.1 Hz, 6H). 13C NMR (126 MHz, Methanol- d 4): δ 170.64, 166.97, 160.72,140.45, 133.21, 131.62, 130.06, 129.69, 127.67, 127.44, 127.09, 126.40,125.92, 108.97, 70.40, 64.44, 61.16, 56.22, 43.57, 42.70, 22.48. HRMS ( m / z ):[M+H] + calcd for C 23 H 25 N4O2S + 421.1698, found 421.1699. Example 25 Preparation of OXR antagonist (compound 78) ; This embodiment provides a method for preparing compound 78, the specific steps of which are as follows: 1) Same as step 15) in Example 8, except that the compound shown in Formula 23 was replaced with the compound shown in Formula 23 (411 mg, 1.0 mmol). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:1) to give 208.8 mg of the compound shown in Formula SI-70, with a yield of 60%.

[0183] The compound represented by formula SI-70 is a yellow oily substance. 1 H NMR (500 MHz, CDCl3): δ 7.37 – 7.27(m, 5H), 5.21 – 5.06 (m, 2H), 4.48 (t, J = 5.8 Hz, 1H), 4.21 – 3.97 (m, 4H), 3.42 (d, J = 12.2 Hz, 1H), 3.39 (d, J = 12.3 Hz, 1H), 1.39 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ 156.73, 156.23, 136.62, 128.49, 128.00, 127.80, 80.81,67.09, 62.76, 62.30, 61.86, 40.62, 28.16. HRMS ( m / z ): [M+Na] +calcd forC 18 H 24 N2NaO5 + 371.1583, found 371.1583. 2) Pyridine (32.3 μL, 0.4 mmol) was added to a DCM (1.0 mL) solution of the compound of formula SI-70 (69.6 mg, 0.2 mmol). DAST (52.8 μL, 0.4 mmol) was added to the reaction solution under an argon atmosphere at -78 °C, and the mixture was stirred at 25 °C for 3 hours. The reaction solution was quenched with water and extracted with DCM (3 × 1.0 mL). The combined organic layers were washed with brine and dried over Na₂SO₄. The solvent was removed under reduced pressure, and the crude product was subjected to rapid silica gel column chromatography (hexane:ethyl acetate, 5:1) to give 49.0 mg of the compound of formula SI-71, in 70% yield.

[0184] The compound shown in formula SI-71 is a white solid with a mp value of 80-81 °C. 1 H NMR (400 MHz, CDCl3): δ7.39 – 7.25 (m, 5H), 5.22 – 5.00 (m, 3H), 4.32 (t, J = 4.5 Hz, 1H), 4.27 (q, J = 4.3, 3.9 Hz, 1H), 4.17 – 4.10 (m, 2H), 3.40 (dd, J = 12.5, 8.0 Hz, 2H),1.39 (s, 9H). 13 C NMR (101 MHz, CDCl3): δ 155.95, 136.55, 128.50, 128.05,127.89, 81.34, 78.39 (d, J = 233.2 Hz), 67.17, 61.96, 40.55, 28.09. Note: a NCO was not observed. 19 F NMR (377 MHz, CDCl3): δ -201.70. HRMS ( m / z ): [M+Na] + calcd for C 18 H 23 FN2NaO4 + 373.1540, found 373.1540. 3) Same as step 1) in Example 13, except that the compound of formula SI-38 was replaced with the compound of formula SI-71 (35.0 mg, 0.1 mmol), and K2CO3 (16.5 mg, 0.12 mmol) and 2-chlorobenzoxazole (15.3 mg, 0.1 mmol) were used. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 3:1) to give 12.9 mg of the compound of formula SI-72, in 40% yield.

[0185] The compound represented by formula SI-72: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 6.33 (s, 1H), 5.16 (dt, J = 58.6, 5.6 Hz, 1H), 4.52 – 4.31 (m, 4H), 3.49 (d, J = 12.7 Hz, 2H), 2.30 (s, 6H), 1.33 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ 166.76, 161.33,156.69, 156.64, 109.52, 80.83, 79.07 (d, J = 222.8 Hz), 62.46, 40.86, 28.07,24.09. HRMS ( m / z ): [M+H] + calcd for C 16 H 24 FN4O2 + 323.1883, found 323.1885. 4) Same as step 3) in Example 17, except that the compound shown in formula SI-53 was replaced with the compound shown in formula SI-72 (12.9 mg, 0.04 mmol). The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:1) to give 10.9 mg of the compound shown in formula 78, with a yield of 67%.

[0186] The compound shown in Formula 78 is a white solid with a mp value of 74-75 °C. 1 H NMR (500 MHz, CDCl3): δ 7.51(dt, J = 7.7, 0.9 Hz, 1H), 7.43 (ddd, J= 7.8, 6.2, 2.6 Hz, 1H), 7.38 – 7.29(m, 2H), 7.21 (ddd, J = 6.3, 4.4, 1.2 Hz, 2H), 6.88 (dd, J = 5.1, 3.6 Hz,1H), 6.35 (s, 1H), 4.82 (ddt, J = 5.7, 4.3, 2.1 Hz, 1H), 4.65 (dt, J = 57.9, 5.7 Hz, 1H), 4.34 (dd, J = 12.8, 2.4 Hz, 1H), 4.09 – 4.04 (m, 1H), 3.68 –3.58 (m, 2H), 3.44 (d, J = 13.0 Hz, 1H), 2.29 (d, J = 25.8 Hz, 6H). 13 C NMR (126 MHz, CDCl3): δ 169.89, 169.86, 160.85, 140.71, 133.67, 131.45, 130.11,129.94, 128.03, 127.76, 127.70, 126.87, 126.18, 109.58, 78.97 (d, J = 230.2Hz), 64.31 (d, J = 22.6 Hz), 61.27 (d, J = 22.8 Hz), 43.87, 42.97, 24.05. 19 FNMR (471 MHz, CDCl3): δ -196.34. HRMS ( m / z ): [M+H] + calcd for C 22 H 22 FN4OS + 409.1498, found 409.1499. Example 26 Preparation of azatidine biosteroid (compound 79) ; This embodiment provides a method for preparing compound 79, the specific steps of which are as follows: 1) Same as step 43) in Example 8, except that 4-(1H-pyrazol-4-yl)-7-((2-(trimethylsilyl)ethoxy)-methyl)-7H-pyrrolo[2,3-D]pyrimidine (31.5 mg, 0.1 mmol) was used instead of 5-chloromethyl-2-oxazolinone. 22.4 mg of the compound of formula SI-73 was obtained by rapid silica gel column chromatography (hexane:ethyl acetate, 1:1), in a yield of 44%.

[0187] The compound shown in formula SI-73 is a pale yellow oily substance. 1 H NMR (500 MHz, CDCl3): δ 8.86 (s,1H), 8.66 (s, 1H), 8.28 (s, 1H), 7.40 (d, J = 3.7 Hz, 1H), 6.82 (d, J = 3.7Hz, 1H), 5.67 (s, 2H), 4.44 (s, 1H), 4.35 (s, 1H), 4.33 (s, 1H), 3.58 – 3.51(m, 2H), 2.65 (s, 1H), 2.48 (d, J = 14.4 Hz, 1H), 2.03 – 1.90 (m, 3H), 1.75(td, J = 8.8, 3.7 Hz, 1H), 1.48 (s, 9H), 0.99 – 0.89 (m, 2H), -0.06 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ 157.19, 152.20, 151.83, 139.38, 128.35, 128.17,114.20, 111.27, 101.04, 80.31, 72.80, 66.90, 66.57, 65.61, 64.06, 28.38,26.07, 24.85, 17.74, 14.28, -1.44. Note: a NCO was not observed. HRMS ( m / z ):[M+H] + calcd for C 26 H 39 N6O3Si + 511.2853, found 511.2855. 2) Same as step 3) in Example 10, except that: the compound of formula SI-73 (30 mg, 0.06 mmol) was used instead of the compound of formula SI-39, and Et3N (50 μL, 0.36 mmol) and ethanesulfonyl chloride (11.6 mg, 0.09 mmol) were added to the mixture instead of DIPEA, 2-thienylbenzoic acid, and HATU. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:2) to give 19.0 mg of the compound of formula SI-74, in 63% yield.

[0188] The compound represented by formula SI-74: a colorless oily substance. 1 H NMR (500 MHz, CDCl3): δ 8.86 (s, 1H), 8.65 (s, 1H), 8.32 (s, 1H), 7.43 (d, J = 3.7 Hz, 1H), 6.83 (d, J = 3.7 Hz,1H), 5.68 (s, 2H), 4.62 (d, J = 2.7 Hz, 2H), 4.35 (s, 1H), 3.59 – 3.52 (m,2H), 3.05 (q, J = 7.4 Hz, 2H), 2.78 (dt, J = 9.6, 5.2 Hz, 2H), 2.31 – 2.18(m, 1H), 2.04 (d, J = 8.4 Hz, 2H), 1.35 – 1.26 (m, 4H), 0.96 – 0.89 (m, 2H), -0.06 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ 152.23, 139.75, 128.81, 126.08,123.41, 114.15, 101.05, 84.29, 72.95, 70.39, 66.73, 65.23, 49.55, 26.60,17.81, 14.61, 8.24, -1.38. Note: NCN were not observed. HRMS ( m / z ): [M+H] + calcd for C 23 H 35 N6O3SSi + 503.2261 was found; 503.2260 was also found. 3) To a THF (1.0 mL) solution of the compound of formula SI-74 (19 mg, 0.04 mmol), TBAF (1 M, THF solution, 0.4 mL, 0.4 mmol) was added. The reaction solution was stirred at 60 °C under an argon atmosphere for 3 hours. The reaction solution was concentrated under vacuum. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:3) to give 11.9 mg of the compound of formula 79, in 80% yield.

[0189] The compound shown in Formula 79 is a colorless oily substance. 1 H NMR (500 MHz, DMSO- d 6): δ 12.10 (s, 1H), 8.89 (s, 1H), 8.69 (s, 1H), 8.39 (s, 1H), 7.59 (dd, J = 3.6, 2.4 Hz, 1H), 7.05 (dd, J = 3.6, 1.7 Hz, 1H), 4.72 (d, J = 2.7 Hz, 2H), 4.49 (s, 1H), 3.05 (q, J = 7.3 Hz, 2H), 2.49 – 2.47 (m, 2H), 2.06 – 1.94 (m, 4H), 1.07 (t, J =7.2 Hz, 3H). 13 C NMR (126 MHz, DMSO- d 6): δ 152.59, 151.40, 150.36, 139.53,130.22, 127.15, 121.70, 113.34, 100.36, 69.50, 64.36, 48.52, 26.15, 14.72,8.48. HRMS ( m / z ): [M+H] + calcd for C 17 H 21 N6O2S + 373.1447, found 373.1449. Example 27 Preparation of azatidine biosteroid (compound 80) ; This embodiment provides a method for preparing compound 79, the specific steps of which are as follows: 1) At 0 °C, NaOH (6.4 mg, 0.16 mmol) was added to a solution of the compound of Formula 52 (24.2 mg, 0.1 mmol) in H2O (0.9 mL) and 1,4-dioxane (0.3 mL). NaNO2 aqueous solution (4.8 M, 95 μL, 0.46 mmol), K3Fe(CN)6 aqueous solution (0.3 M, 65.8 μL, 0.02 mmol), and Na2S2O8 (26.2 mg, 0.11 mmol) were added to the mixture. The mixture was stirred at 25 °C for 12 hours. After the reaction was complete, the reaction mixture was extracted with DCM (3 × 3 mL). The combined organic layers were washed with brine and dried over Na2SO4. The solvent was removed under reduced pressure, and the crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 10:1) to give 23.0 mg of the compound of Formula SI-75 in 80% yield.

[0190] The compound represented by formula SI-75 is a yellow oily substance. 1 H NMR (500 MHz, CDCl3): δ 4.92 (s, 2H), 2.59 (d, J = 74.0 Hz, 2H), 2.11 (ddd, J = 14.9, 8.9, 5.3 Hz, 2H), 1.67 – 1.59(m, 2H), 1.47 (s, 9H). 13 C NMR (126 MHz, CDCl3): δ 154.92, 110.46, 82.13,68.53, 67.70, 28.15, 22.93, 21.89, 12.04. HRMS ( m / z ): [M+Na] + calcd forC 11 H 17 N3NaO6 + 310.1015, found 310.1013. 2) Same as step 2) in Example 26, except that: the compound shown in formula SI-75 (23 mg, 0.08 mmol) was used instead of the compound shown in formula SI-73, bromoacetyl bromide (24.2 mg, 0.12 mmol) was used instead of ethanesulfonyl chloride, and Et3N (66.6 μL, 0.48 mmol) was used. The crude product was subjected to silica gel rapid column chromatography (hexane:ethyl acetate, 1:1) to give 17.2 mg of the compound shown in formula 80, with a yield of 70%.

[0191] The compound shown in Formula 80:1 H NMR (400 MHz, Methanol- d 4): δ 5.45 (d, J = 4.6 Hz, 1H), 5.19 (d, J = 4.7 Hz, 1H), 3.95 – 3.81 (m, 2H), 2.64 – 2.42 (m, 2H), 2.17(tt, J = 18.8, 7.2 Hz, 2H), 1.74 (ddq, J = 19.7, 9.7, 4.9 Hz, 1H), 1.55 (dtt, J = 15.0, 9.2, 5.7 Hz, 1H). 13 C NMR (126 MHz, Methanol- d 4): δ 166.67, 110.59,70.60, 68.12, 25.42, 24.08, 23.57, 12.22. HRMS ( m / z ): [M+Na] + calcd forC8H 10 BrN3NaO5 + 329.9702, found 329.9700. Efficacy Validation 1: IP1 HTRF Antagonist Test in HEK293 / OX1R+Gq and HEK293 / OX2R+Gq Stable Cell Lines The purpose of this experiment was to investigate the efficacy and effectiveness of the compound in antagonistic mode against HEK293 / OX1R+Gq and HEK293 / OX2R+Gq stable cell lines. All specific testing and analysis were performed by Sandia Biosciences. Gq is a type of G protein; OX1R and OX2R require binding to Gq protein to induce changes in calcium flux. Since Gq protein is scarce in cells, it was co-transfected to increase signal levels.

[0192] The experimental steps are as follows: 1. Compound preparation 1) Dissolve the solid compounds (67-78, SI-44, SI-46, SI-49, SI-51) prepared in Examples 10-25 above in 100% DMSO to prepare a 10 mM stock solution. Store in a nitrogen tank (at room temperature).

[0193] 2) Dilute the compound from 10 mM to the target concentration using DMSO.

[0194] 3) Perform a 3-fold serial dilution using Bravo on 384 LDV plates (5 μL of compound dissolved in 10 μL of DMSO).

[0195] 2. Obtaining and culturing cell lines We commissioned Sandia Biotechnology to prepare HEK293 / OX1R+Gq (HEK293 cells expressing OX1R and Gq) and HEK293 / OX2R+Gq cell lines (HEK293 cells expressing OX2R and Gq) using conventional methods, and then cultured them using conventional methods.

[0196] 3. Cell collection 1) When collecting cells from a 15cm culture dish, the confluence should be close to 80%.

[0197] 2) Discard the culture medium and gently rinse the petri dish with PBS.

[0198] 3) Add 4 mL of 0.05% trypsin (dilute 0.25% trypsin-EDTA 5 times with PBS), and incubate at 37°C and 5% CO2 until cells detach.

[0199] 4) Add 8 mL of culture medium and pipette up and down until the cells are evenly dispersed in the solution.

[0200] 5) Centrifuge the cell suspension at 1000 rpm for 5 minutes.

[0201] 6) After centrifugation, discard the supernatant. Resuspend the cell pellet in 10-15 mL of cell culture medium, incubate the centrifuge tube at 37°C and 5% CO2 for 2 hours, and then wash twice with PBS before use.

[0202] 4. IP-1 HTRF Detection 1) Calculate the volume of stimulation buffer required to resuspend the cell pellet to achieve the optimal cell density (15,000 cells / well).

[0203] 2) Add 15 nL of the diluted compound to the detection plate (784075) using ECHO.

[0204] 3) Seed 7 μL of resuspended cells (15,000 cells / well) into a detection plate containing 15 nL of compound and incubate at 37°C for 30 minutes.

[0205] 4) Add 7uL EC80 OrexinA to the detection plate and incubate at 37°C for 2 hours.

[0206] 5) Add 3uL of IP1-d2 (diluted 20 times before use) to the detection plate and centrifuge at 1000 rpm for 1 minute.

[0207] 6) Add 3uL of Anti-IP1-Cryptate (diluted 20 times before use) to the detection plate and centrifuge at 1000 rpm for 1 minute.

[0208] Use Envision to read the board.

[0209] The inhibitory activity test results of the solid compounds (67-78, SI-44, SI-46, SI-49, SI-51) prepared in Examples 10-25 above against OX1R and OX2R are shown in Table 1 below.

[0210] ; Efficacy Verification 2: JAK Kinase 2 (JAK2) Biochemical Detection The purpose of this experiment was to determine the potency and efficacy of small molecule compounds in inhibiting JAK kinase 2 (JAK2). All specific testing and analysis were outsourced to Sandia Pharmaceuticals.

[0211] The experimental steps are as follows: 1. Buffer preparation 1x Enzyme Buffer: Prepared by diluting 5x enzyme buffer with distilled water. Its components include 50mM HEPES, pH 7.0; 0.02% sodium azide; 0.01% bovine serum albumin; and 0.1mM orthovanadate. A suitable amount of buffer should be freshly prepared before the experiment. Additionally, 5mM MgCl2 and 1mM DTT should be added to this buffer to a final concentration.

[0212] 2. Compound Preparation 1) The compound of formula 79 prepared in Example 26 was dissolved in 100% DMSO to prepare a stock solution with a concentration of 10 mM.

[0213] 2) Take an appropriate amount from the stock solution and dilute it with 100% DMSO to a stock solution with a concentration of 1mM.

[0214] 3) On the day of the experiment, the BRAVO liquid handling workstation was used to start with mM DMSO stock solution and dilute the compound with DMSO in 384-well low dead volume microplates: the initial concentration was 1mM, the 3-fold gradient dilution method was used, and 10 dose gradients were set.

[0215] 4) Centrifuge at 1000 rpm for 1 minute.

[0216] 5) Using the Echo pipetting system, transfer 100 nmL of the compound from a 384-well LDV plate to a 384-well low-volume white microplate to prepare the assay plate. Then add 5 μL of enzyme solution and 5 μL of substrate solution to the assay plate. The initial concentration of the compound in this assay plate is 10 μM, with 3-fold serial dilutions and 10 dose gradients, all in duplicate. The final concentration of DMSO in the assay system is 1%.

[0217] 3. Preparation of JAK2 enzyme working solution 1) Prepare the JAK2 enzyme working solution using 1x enzyme buffer, with a working concentration of 0.045 ng / μL for JAK2. Use a pipette to add 5 μL of JAK2 enzyme working solution to each compound well and high signal well of the detection plate; for low signal wells, add 5 μL of 1x enzyme buffer instead of the enzyme solution (to set the signal baseline).

[0218] 2) Centrifuge at 1000 rpm for 1 minute.

[0219] 3) The compound and enzyme were pre-incubated at room temperature for 15 minutes.

[0220] 4. Preparation of TK-Biotin Substrate and ATP Working Solution 1) Prepare a mixed working solution of TK-Biotin substrate and ATP using 1x enzyme buffer: the working concentration of ATP in the mixed solution is 14μM and the working concentration of TK-Biotin substrate is 4μM.

[0221] 2) Use a pipette to add 5 μL of the above mixed working solution to each well (including the low signal well) of the detection plate.

[0222] 3) Centrifuge the test plate at 1000 rpm for 1 minute, and then react at room temperature for 45 minutes.

[0223] 5. Detection of the preparation of the mixture 1) Prepare the detection mixture using the 1x detection buffer provided in the kit: the working concentration of streptavidin-XL665 is 0.25 μM, and the working concentration of TK antibody-caecin compound is 0.5x.

[0224] 2) Use a pipette to add 10 μL of detection mixture to each well of the detection plate (including the low signal well).

[0225] 3) Centrifuge the test plate at 1000 rpm for 1 minute.

[0226] 4) After adding the test reagent, place the test plate on the Envision microplate reader to read the HTRF signal (the 665 / 620 ratio of the HTRF signal is calculated from the intensity of emission light 1 at 665nm and emission light 2 at 620nm).

[0227] The inhibitory activity test results of the compound shown in Formula 79 against JAK2 are as follows: IC50 50 = 971.71 nM.

[0228] The above description of the embodiments is provided to enable those skilled in the art to understand and use the invention. It will be apparent to those skilled in the art that various modifications can be made to these embodiments, and the general principles described herein can be applied to other embodiments without inventive effort. Therefore, the present invention is not limited to the above embodiments, and any improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the invention should be within the protection scope of the present invention.

Claims

1. A tricyclic compound, characterized in that, The structure of the compound is shown in Formula I below: I； Wherein, n is a positive integer from 0 to 2; R1 is any one of CH or N; R2 is any one of H, an amino protecting group, or a substituted or unsubstituted carboxyl group, wherein the substituted group is a C1-C10 alkyl group.

2. An intermediate compound a, characterized in that, The structure of the compound is shown in Formula II-1 below: II-1; Wherein, n is a positive integer from 0 to 2; R1 is any one of CH and N; R2 is any one of H, amino protecting group, substituted or unsubstituted carboxyl group, wherein the substituted group is a C1-C10 alkyl group; R3, R4, and R5 are any one of the following 1)-4): 1) R3 is OH, and R4 and R5 are bonded to form an epoxy group (-O-); 2) R3 and R4 are both OH or OMs, and R5 is N3 or NH2; 3) R3 and R5 are both OH or OMs, and R4 is N3; 4) R3 and R4 are connected to form -N=PPh3- or -NH-, and R5 is OMs.

3. An intermediate compound b, characterized in that, The structure of the compound is shown in formula II-2, II-3, II-4 or II-5: II-2; II-3; II-4; II-5; In formula II-2, when n=1, R1 is CH and R2' is any one of substituted or unsubstituted carboxyl groups, wherein the substituted group is a C1-C10 alkyl group; or when R1 is N, R2' is an amino protecting group. When n=0 or 2, R1 is CH and R2 is H.

4. A method for preparing the tricyclic compound according to claim 1, characterized in that, Includes the following steps: A1. Reaction of the compound shown in formula II-2 of claim 3 with mCPBA yields intermediate compound a, which is shown in claim 2, where R3 is OH and R4 and R5 are connected to form an epoxy group (-O-), and is called compound a-1; A2. Compound a-1 is subjected to a ring-opening reaction with KN3 to obtain intermediate compound a, where R3 and R4 are both OH and R5 is N3, as shown in claim 2, or intermediate compound a, where R3 and R5 are both OH and R4 is N3, is called compound a-2. A3. Compound a-2 is subjected to methanesulfonation to obtain intermediate compound a, where R3 and R4 are both OMs and R5 is N3, as shown in claim 2, or intermediate compound a, where R3 and R5 are both OMs and R4 is N3, is called compound a-3. A4. Reaction of compound a-3 with PPh3 yields compound a, which is an intermediate of OMs, as shown in claim 2, with R3 and R4 linked to form -N=PPh3- and R5 being an intermediate of OMs. This compound is called compound a-4. Then, compound a-4 is reacted with t-BuOK to yield the corresponding tricyclic compound as shown in claim 1. Alternatively, reaction of compound a-4 with a strong base yields compound a, which is an intermediate of OMs, as shown in claim 2, with R3 and R4 linked to form -NH- and R5 being an intermediate of OMs. This compound is called compound a-5. Then, compound a-5 is reacted with t-BuOK to yield the corresponding tricyclic compound as shown in claim 1. A5. Compound a-3 is subjected to hydrogenation to obtain intermediate compound a, where R3 and R4 are both OMs and R5 is NH2, as shown in claim 2, or intermediate compound a, where R3 and R5 are both OMs and R4 is NH2, is called compound a-6; then compound a-6 is reacted with PhLi to obtain the corresponding tricyclic compound shown in claim 1. Preferably, the compound of formula II-3 in claim 3 is reacted with a salt containing an amino protecting group to obtain the compound of formula II-2 in claim 3, where n=1, R1 is N, and R2' is an amino protecting group; or The compound shown in Formula II-4 of claim 3 is reacted with DBU to generate the compound shown in Formula II-5 of claim 3. Then, the compound shown in Formula II-5 is reacted with an alcohol to obtain the compound shown in Formula II-2 of claim 3, where n=1, R1 is C, and R2' is a substituted or unsubstituted carboxyl group.

5. The use of the tricyclic compound according to claim 1 in the preparation of ABCA derivatives.

6. An ABCA derivative, characterized in that, The structure of the ABCA derivative is shown in formula III-1, III-2 or III-3 as follows: III-1; III-2; III-3; Where n is a positive integer from 0 to 2; R6 is an amino protecting group; The groups of R7 and R8 are as follows: when R7 is CH, R8 is H, a substituted or unsubstituted ester group, a substituted or unsubstituted carboxyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted hydroxyl group; when R7 is N, R8 is an amino protecting group or a substituted or unsubstituted aryl group. R9 is any one of H or its isotopes, halogens, substituted or unsubstituted amides, substituted or unsubstituted alkyl groups, substituted or unsubstituted hydroxyl groups, substituted or substituted N heterocycles, substituted or substituted amino groups, alkyl sulfides, aryl sulfides, alkylamines, arylamines, and selenium. R10 is any one of substituted or unsubstituted aromatic rings, substituted or unsubstituted amides, substituted or unsubstituted N-heterocycles, substituted or unsubstituted amino groups, and substituted or unsubstituted alkyl groups; R11 and R12 are both NO2.

7. A method for preparing the ABCA derivative according to claim 6, characterized in that, Includes the following steps: B1. Substitute the tricyclic compound of claim 3 to obtain the ABCA derivative shown in formula III-1; B2. The ABCA derivative shown in Formula III-1 is subjected to a stereoselective transition metal catalytic reaction to obtain the ABCA derivative shown in Formula III-2; during the reaction, compound SI-40 or SI-41 is added. B3. Nitrogenate the ABCA derivative shown in Formula III-1 to obtain the ABCA derivative shown in Formula III-3.

8. The use of an ABCA derivative according to claim 6 in the preparation of orexin receptor (OXR) antagonists or azatidine biosteroids or electron isosteres.

9. An orexin receptor (OXR) antagonist, characterized in that, The structure of the OXR antagonist is shown in formula IV-1 or IV-2 as follows: IV-1; IV-2; Where n is a positive integer from 0 to 2; The groups of R7 and R8 are as follows: when R7 is CH, R8 is H, a substituted or unsubstituted ester group, a substituted or unsubstituted carboxyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted hydroxyl group; when R7 is N, R8 is an amino protecting group or a substituted or unsubstituted aryl group; R9 is H or its isotope, halogen, a substituted or unsubstituted amide, a substituted or unsubstituted alkyl group, a substituted or unsubstituted hydroxyl group, a substituted or substituted N heterocycle, a substituted or substituted amino group, an alkyl sulfide, an aryl sulfide, an alkylamine, an arylamine, or selenium. R10 is any one of substituted or unsubstituted aromatic rings, substituted or unsubstituted amides, substituted or unsubstituted N-heterocycles, substituted or unsubstituted amino groups, and substituted or unsubstituted alkyl groups; R13 is R14 is , or .

10. A method for preparing an orexin receptor (OXR) antagonist, characterized in that, Includes the following steps: The ABCA derivatives shown in Formula III-1 or III-2 are obtained by substituting the R6 group.

11. An azatidine biosteroid, characterized in that, The structure of the azatidine biosteroid is shown in formula IV-3 or IV-4 below: IV-3; IV-4; Where n is a positive integer from 0 to 2; The groups of R7 and R8 are as follows: when R7 is CH, R8 is H, a substituted or unsubstituted ester group, a substituted or unsubstituted carboxyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted hydroxyl group; when R7 is N, R8 is an amino protecting group or a substituted or unsubstituted aryl group. R10 is R14 is ; R11 and R12 are both NO2; R15 is COCH2R16, where R16 is a halogen.

12. A method for preparing azatidine biosteroids, characterized in that, Includes the following steps: Set R10 as The ABCA derivative shown in Formula III-2 undergoes a substitution reaction of the R6 group, followed by the substitution of the SEM group with H, to obtain the product; or The ABCA derivative shown in Formula III-3 is obtained by substituting the R6 group.

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