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【结 构 式】 
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【药物名称】SR-125329, SSR-125329A 【化学名称】N-[3-[4-(2-Adamantyl)-3,5-dichlorophenyl]-2(Z)-propenyl]-N-cyclohexyl-N-ethylamine 【CA登记号】313510-43-9, 313511-26-1 (fumarate), 313510-02-0 (hydrochloride), 313511-27-2 (maleate) 【 分 子 式 】C27H37Cl2N 【 分 子 量 】446.50864 |
【开发单位】Sanofi-synthélabo (Originator) 【药理作用】Antiarthritic Drugs, IMMUNOMODULATING AGENTS, Immunomodulators, Rheumatoid Arthritis, Treatment of, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, sigma-Receptor Ligands |
合成路线1
Preparation of the intermediate aryl triflate (V) is shown is Scheme 29890101a. The dilithiated derivative of 4-bromo-3,5-dichlorophenol (I) is condensed with 2-adamantanone (II) to produce the carbinol adduct (III). Reduction of the tertiary alcohol of (III) by means of concentrated HI in boiling AcOH leads to the adamantanyl phenol (IV). This is then reacted with trifluoromethanesulfonic anhydride in cold pyridine to yield sulfonate (V).
| 【1】 Paul, R.; Boigegrain, R.; Nisato, D.; Casellas, P.; Herbert, J.M.; Bourrie, B.; Bourrie, M.; Lair, P.; Vernieres, J.C. (Sanofi-Synthélabo); Benzene derivs., preparation method and pharmaceutical compsns. containing same. EP 1192122; FR 2794742; JP 2003502306; US 6482986; WO 0076953 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 62827 | 4-bromo-3,5-dichlorophenol | C6H3BrCl2O | 详情 | 详情 | |
| (II) | 40404 | 2-adamantanone | 700-58-3 | C10H14O | 详情 | 详情 |
| (III) | 62828 | 2-(2,6-dichloro-4-hydroxyphenyl)tricyclo[3.3.1.13,7]decan-2-ol | C16H18Cl2O2 | 详情 | 详情 | |
| (IV) | 62829 | 3,5-dichloro-4-tricyclo[3.3.1.13,7]dec-2-ylphenol | C16H18Cl2O | 详情 | 详情 | |
| (V) | 62830 | 3,5-dichloro-4-tricyclo[3.3.1.1~3,7~]dec-2-ylphenyl trifluoromethanesulfonate | C17H17Cl2F3O3S | 详情 | 详情 |
合成路线2
Alkylation of cyclohexyl ethylamine (VI) with propargyl bromide (VII) gives the tertiary amine (VIII). Then, palladium-catalyzed coupling between the propargylic amine (VIII) and aryl triflate (V) furnishes the disubstituted acetylene derivative (IX). Finally, semihydrogenation of the triple bond of (IX) in the presence of cyclohexene and Lindlar catalyst gives rise to the target cis-olefin.
| 【1】 Paul, R.; Boigegrain, R.; Nisato, D.; Casellas, P.; Herbert, J.M.; Bourrie, B.; Bourrie, M.; Lair, P.; Vernieres, J.C. (Sanofi-Synthélabo); Benzene derivs., preparation method and pharmaceutical compsns. containing same. EP 1192122; FR 2794742; JP 2003502306; US 6482986; WO 0076953 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 62830 | 3,5-dichloro-4-tricyclo[3.3.1.1~3,7~]dec-2-ylphenyl trifluoromethanesulfonate | C17H17Cl2F3O3S | 详情 | 详情 | |
| (VI) | 59245 | N-Ethylcyclohexanamine; N-Ethylcyclohexylamine; Vulkacit HX | 5459-93-8 | C8H17N | 详情 | 详情 |
| (VII) | 11176 | 3-Bromopropyne; 3-Bromo-1-propyne | 106-96-7 | C3H3Br | 详情 | 详情 |
| (VIII) | 62831 | N-ethyl-N-(2-propynyl)cyclohexanamine; N-cyclohexyl-N-ethyl-N-(2-propynyl)amine | C11H19N | 详情 | 详情 | |
| (IX) | 62832 | N-[3-(3,5-dichloro-4-tricyclo[3.3.1.1~3,7~]dec-2-ylphenyl)-2-propynyl]-N-ethylcyclohexanamine; N-cyclohexyl-N-[3-(3,5-dichloro-4-tricyclo[3.3.1.1~3,7~]dec-2-ylphenyl)-2-propynyl]-N-ethylamine | C27H35Cl2N | 详情 | 详情 |