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【结 构 式】 
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【药物名称】BRL-20627 【化学名称】(2alpha,6beta,9aalpha)-(±)-4-Amino-5-chloro-2-methoxy-N-(octahydro-6-methyl-2H-quinolizin-2-yl)benzamide hydrochloride 【CA登记号】99390-76-8 【 分 子 式 】C18H27Cl2N3O2 【 分 子 量 】388.34079 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】Nausea and Vomiting, Treatment of, NEUROLOGIC DRUGS |
合成路线1
The reaction of quinolizidinone (I) with hydroxylamine and pyridine in refluxing ethanol gives the corresponding oxime (II), which is reduced with LiAlH4 in ether to yield 6-methyl-2-aminoquinolizidine (III). The acylation of (III) with 4-acetamido-5-chloro-2-methoxybenzoyl chloride (IV) [prepared from the corresponding acid (V) and SOCl2] by means of triethylamine in benzene affords the protected benzamide (VI), which is finally deprotected with KOH in refluxing ethanol.
| 【1】 Hadley, M.S.; Watts, E.A. (SmithKline Beecham plc); Treating gastro-intestinal disorders and emesis with n-(heterocyclic substituted)benzamides. BE 0860049; DE 2748260; FR 2370051; GB 1593146; JP 53059692; NL 7712203; US 4213983 . |
| 【2】 Singh, S.K.; Kumar, Y.; Prasad, M.; Prasad, A.; Kumar, N.P. (Ranbaxy Laboratories Ltd.); Process for the preparation of cefdinir. WO 0391261 . |
| 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) | 29171 | 6-methyloctahydro-2H-quinolizin-2-one | C10H17NO | 详情 | 详情 | |
| (II) | 29172 | 6-methyloctahydro-2H-quinolizin-2-one oxime | C10H18N2O | 详情 | 详情 | |
| (III) | 29173 | 6-methyloctahydro-2H-quinolizin-2-amine | C10H20N2 | 详情 | 详情 | |
| (IV) | 11631 | 4-(Acetamido)-5-chloro-2-methoxybenzoyl chloride | C10H9Cl2NO3 | 详情 | 详情 | |
| (V) | 29174 | 4-(acetamido)-5-chloro-2-methoxybenzoic acid | C10H10ClNO4 | 详情 | 详情 | |
| (VI) | 29175 | 4-(acetamido)-5-chloro-2-methoxy-N-(6-methyloctahydro-2H-quinolizin-2-yl)benzamide | C20H28ClN3O3 | 详情 | 详情 |