【结 构 式】 |
【药物名称】S-35836-1 【化学名称】N,N-Dimethylcarbamic acid 2-[1-(dimethylamino)cyclopropyl]ethyl ester fumarate 【CA登记号】387844-54-4, 387844-53-3 (free base) 【 分 子 式 】C14H24N2O6 【 分 子 量 】316.35718 |
【开发单位】Servier (Originator) 【药理作用】Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, Nicotinic Receptor Agonists |
合成路线1
Partial hydrolysis of dimethyl 1,1-cyclopropanedicarboxylate (I) yields mono-acid (II). Curtius rearrangement of (II), followed by treatment with methanol provides the methyl carbamate (III), which is N-methylated to (IV) employing iodomethane and NaH in DMF. Reduction of the carboxylate and carbamate groups of (IV) by means of LiAlH4 furnishes amino alcohol (V). After chlorination of (V) with SOCl2, the resultant alkyl chloride (VI) is displaced by NaCN to afford nitrile (VII). Hydrolysis of (VII) with methanolic HCl leads to ester (VIII), which is further reduced to amino alcohol (IX) using LiAlH4. Acylation of alcohol (IX) with dimethylcarbamoyl chloride produces the target amino carbamate, which is finally isolated as the corresponding fumarate salt.
【1】 Guillonneau, C.; Lestage, P.; Charton, Y.; Lockhart, B.; Goldstein, S. (Servier Laboratoires); 1,1- And 1,2-disubstd. cyclopropanes, process for their preparation and pharmaceutical compsns. thereof. EP 1170281; FR 2810664; JP 2002069046; US 2002022643 . |
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) | 58458 | dimethyl 1,1-cyclopropanedicarboxylate; cyclopropane-1,1-dicarboxylic acid dimethyl ester; 1,1-cyclopropanedicarboxylic acid dimethyl ester | 6914-71-2 | C7H10O4 | 详情 | 详情 |
(II) | 58459 | 1-(methoxycarbonyl)cyclopropanecarboxylic acid | 113020-21-6 | C6H8O4 | 详情 | 详情 |
(III) | 58460 | methyl 1-[(methoxycarbonyl)amino]cyclopropanecarboxylate | C7H11NO4 | 详情 | 详情 | |
(IV) | 58461 | methyl 1-[(methoxycarbonyl)(methyl)amino]cyclopropanecarboxylate | C8H13NO4 | 详情 | 详情 | |
(V) | 58462 | [1-(dimethylamino)cyclopropyl]methanol | C6H13NO | 详情 | 详情 | |
(VI) | 58463 | 1-(chloromethyl)-N,N-dimethylcyclopropanamine; N-[1-(chloromethyl)cyclopropyl]-N,N-dimethylamine | C6H12ClN | 详情 | 详情 | |
(VII) | 58464 | 2-[1-(dimethylamino)cyclopropyl]acetonitrile | C7H12N2 | 详情 | 详情 | |
(VIII) | 58465 | methyl 2-[1-(dimethylamino)cyclopropyl]acetate | C8H15NO2 | 详情 | 详情 | |
(IX) | 58466 | 2-[1-(dimethylamino)cyclopropyl]-1-ethanol | C7H15NO | 详情 | 详情 |