Vamicamide, FK-176, Urocut
(2R,4R)-4-二甲基氨基-2-苯基-2-吡啶-2-基戊酰胺Chemical Name: (?-(R*)-alpha-[(R*)-2-(Dimethylamino)propyl]-alpha-phenyl-2-pyridineacetamide; (?-(2R*,4R*)-4-(Dimethylamino)-2-phenyl-2-(2-pyridyl)pentanamide
CAS No. 132373-81-0
项目整合开发状态: Phase III
项目研究机构: Fujisawa (Originator)
合成路线:Vamicamide is synthesized by two closely related ways (1).Scheme 1: 1) The alkylation of 2-phenyl-2-(2-pyridyl)acetonitrile (I) with chloroacetone (II) is achieved in the presence of KOH in DMSO to give the 4-oxopentanenitrile derivative (III).Compound (III) is then converted to (V) by reaction with dimethylamine (IV) using titanium tetrachloride and successive reduction with NaBH4.The nitrile (V) (a mixture of two diastereoisomers) is hydrolyzed with concentrated H2SO4 in acetic acid to give the final pentanamide derivative as a racemic mixture of two diastereoisomers,A-racemate and B-racemate.Separation is accomplished by recrystallization of their maleic acid salts.The racemates are resolved by recrystallization with (-)-dibenzoyl-L-tartaric acid.2) The reaction of 2-phenyl-2-(2-pyridyl)acetonitrile (I) with 2-(dimethylamino)propylchloride (VI) using a base affords the intermediate (V),which is hydrolyzed with concentrated sulfuric acid in acetic acid to give the final pentanamide derivative as a mixture of two diastereoisomers.These are resolved by recrystallization.
📌 参考资料/链接：
参考文献标题:Synthesis and anticholinergic activity of the four stereoisomers of 4-(dimethylamino)-2-phenyl-2-(2-pyridyl)pentanamide
文献作者:Akahane,A.; Tada,T.; Matsuo,M.; Nagano,M.; Oyasu,H.; Tomoi,M.
参考来源:J Med Chem 1994,37(9),1378-81
📄 详细内容
合成路线:Vamicamide is synthesized by two closely related ways (1).Scheme 1: 1) The alkylation of 2-phenyl-2-(2-pyridyl)acetonitrile (I) with chloroacetone (II) is achieved in the presence of KOH in DMSO to give the 4-oxopentanenitrile derivative (III).Compound (III) is then converted to (V) by reaction with dimethylamine (IV) using titanium tetrachloride and successive reduction with NaBH4.The nitrile (V) (a mixture of two diastereoisomers) is hydrolyzed with concentrated H2SO4 in acetic acid to give the final pentanamide derivative as a racemic mixture of two diastereoisomers,A-racemate and B-racemate.Separation is accomplished by recrystallization of their maleic acid salts.The racemates are resolved by recrystallization with (-)-dibenzoyl-L-tartaric acid.2) The reaction of 2-phenyl-2-(2-pyridyl)acetonitrile (I) with 2-(dimethylamino)propylchloride (VI) using a base affords the intermediate (V),which is hydrolyzed with concentrated sulfuric acid in acetic acid to give the final pentanamide derivative as a mixture of two diastereoisomers.These are resolved by recrystallization.
参考文献标题:Vamicamide
文献作者:Mealy,N.; Castar,J.
参考来源:Drugs Fut 1995,20(10),1018
产品链接: CAS No. 132373-81-0››