【结 构 式】 |
【药物名称】YNS-15P 【化学名称】(2R,11bS)-N-(9-Methoxy-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizin-2-yl)-N-methylmethanesulfonamide hydrochloride 【CA登记号】198954-06-2, 198953-89-8 (trans-isomer; monoHCl) 【 分 子 式 】C16H25ClN2O3S 【 分 子 量 】360.90625 |
【开发单位】Nippon Shinyaku (Originator) 【药理作用】GASTROINTESTINAL DRUGS, Irritable Bowel Syndrome, Agents for, alpha2-Adrenoceptor Antagonists |
合成路线1
3-Methoxyphenethylamine (I) was converted into formamide (II) upon refluxing in ethyl formate. Subsequent cyclization of (II) in hot polyphosphoric acid produced the dihydroisoquinoline (III). This was subjected to a tandem Mannich-Michael condensations by refluxing in methyl vinyl ketone (IV) to yield the benzoquinolizinone system (V). The desired (S)-enantiomer (VI) was then isolated by crystallization of the diastereoisomeric salts with (-)-di-p-toluoyl-L-tartaric acid in EtOAc. Condensation of (VI) with methylamine in the presence of TiCl4, followed by reduction of the intermediate imine with NaBH4 provided amine (VII). This was finally converted to the target sulfonamide by treatment with methanesulfonyl chloride and Et3N.
【1】 Yamamoto, O.; Shirouchi, Y. (Nippon Shinyaku Co., Ltd.); Benzoquinolizine derivs. and medicinal compsns.. EP 0897923; WO 9740046 . |
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) | 37185 | 2-(3-methoxyphenyl)-1-ethanamine; 3-methoxyphenethylamine | 2039-67-0 | C9H13NO | 详情 | 详情 |
(II) | 41118 | 3-methoxyphenethylformamide | C10H13NO2 | 详情 | 详情 | |
(III) | 41119 | 6-methoxy-3,4-dihydroisoquinoline; 3,4-dihydro-6-isoquinolinyl methyl ether | C10H11NO | 详情 | 详情 | |
(IV) | 30324 | 3-buten-2-one; methyl vinyl ketone | 78-94-4 | C4H6O | 详情 | 详情 |
(V) | 41120 | 9-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one | C14H17NO2 | 详情 | 详情 | |
(VI) | 41121 | (11bS)-9-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one | C14H17NO2 | 详情 | 详情 | |
(VII) | 41122 | (2R,11bS)-9-methoxy-N-methyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-amine; N-[(2R,11bS)-9-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl]-N-methylamine | C15H22N2O | 详情 | 详情 |