Brofaromine hydrochloride, CGP-11305A, Consonar
溴法罗明 溴法诺明 Chemical Name: 4-(7-Bromo-5-methoxy-2-benzofuranyl)piperidine hydrochloride
CAS No. 63638-90-4, 63638-91-5 (free base)
项目整合开发状态: Phase III
项目研究机构: Novartis (Originator)
合成路线:Bromination of 2-hydroxy-5-methoxybenzaldehyde (I) in acetic acid / sodium acetate mixture gives bromoaldehyde (II).Condensation to the benzofuranylpyridine (IV) is achieved by heating a solution of (II) and 4-(chloromethyl)pyridine hydrochloride (III) in polyethylene glycol-400 in the presence of potassium carbonate.Quaternization of (IV) with dimethylsulfate in dichloromethane affords (V),which upon reduction with sodium borohydride gives intermediate (VI).Reduction of (VI) with platinum on charcoal in methanol/HBr solution yields the N-methylpiperidine (VII).Degradation of the N-methyl group with ethylchloroformate in toluene affords the carbamate (VIII).Final treatment of (VIII) with potassium hydroxide in n-butanol yields the free base of brofaremine,which is converted to its hydrochloride salt by treatment with hydrochloric acid in methanol.
📌 参考资料/链接：
参考文献标题:Tetrahydropyridine and piperidine derivatives and processes for the preparation thereof
文献作者:Schenker,K.; Bernasconi,R.(Novartis AG)
参考来源:DE 2653147; ES 453582; FR 2332754; GB 1565055; JP 52065277
📄 详细内容
合成路线:Bromination of 2-hydroxy-5-methoxybenzaldehyde (I) in acetic acid / sodium acetate mixture gives bromoaldehyde (II).Condensation to the benzofuranylpyridine (IV) is achieved by heating a solution of (II) and 4-(chloromethyl)pyridine hydrochloride (III) in polyethylene glycol-400 in the presence of potassium carbonate.Quaternization of (IV) with dimethylsulfate in dichloromethane affords (V),which upon reduction with sodium borohydride gives intermediate (VI).Reduction of (VI) with platinum on charcoal in methanol/HBr solution yields the N-methylpiperidine (VII).Degradation of the N-methyl group with ethylchloroformate in toluene affords the carbamate (VIII).Final treatment of (VIII) with potassium hydroxide in n-butanol yields the free base of brofaremine,which is converted to its hydrochloride salt by treatment with hydrochloric acid in methanol.
参考文献标题:Brofaremine Hydrochloride
文献作者:Waldmeier,P.C.; Schilling,W.
参考来源:Drugs Fut 1985,10(5),371
产品链接: CAS No. 63638-90-4›› 产品链接: CAS No.63638-91-5››