OPC-51803
2-[1-[2-氯-4-(1-吡咯里二基)苯甲酰]-2,3,4,5-四氢-1H-苯甲西平-5(R)-基]-N-异丙基乙酰胺Chemical Name: 2-[1-[2-Chloro-4-(1-pyrrolidinyl)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepin-5(R)-yl]-N-isopropylacetamide
CAS No. 192514-54-8, 192514-02-6 (undefined isomer)
项目整合开发状态: Phase II
项目研究机构: Otsuka (Originator)
合成路线:Horner-Emmons condensation of benzazepinone (I) with triethyl phosphonoacetate gave unsaturated ester (II).Subsequent reductive treatment of (II) with Mg in MeOH produced the saturated ester (III) with concomitant cleavage of the tosyl group.2-Chloro-4-(1-pyrrolidinyl)benzoyl chloride (V) (prepared by reaction of the corresponding carboxylic acid (IV) with SOCl2) was then condensed with benzazepine (III) to produce benzamide (VI).Hydrolysis of the methyl ester function of (VI) yielded the racemic carboxylic acid (VII),which was resolved by means of esterification with (R)-2-heptanol,followed by chromatographic separation of the diastereomeric mixture.After saponification of the required diastereoisomeric ester (VIII),the resulting (R)-carboxylic acid was finally coupled with isopropylamine using diethylcyanophosphate as the condensing reagent.
📌 参考资料/链接：
参考文献标题:Benzazepine derivs.with vasopressin agonistic activity
文献作者:Ogawa,H.; Kondo,K.; Shinohara,T.; Kan,K.; Tanada,Y.; Kurimura,M.; Morita,S.; Uchida,M.; Mori,T.; Tominaga,M.; Yabuuchi,Y.(Otsuka Pharmaceutical Co.,Ltd.)
参考来源:EP 0877736; JP 1998081668; US 6096736; WO 9722591
📄 详细内容
合成路线:Horner-Emmons condensation of benzazepinone (I) with triethyl phosphonoacetate gave unsaturated ester (II).Subsequent reductive treatment of (II) with Mg in MeOH produced the saturated ester (III) with concomitant cleavage of the tosyl group.2-Chloro-4-(1-pyrrolidinyl)benzoyl chloride (V) (prepared by reaction of the corresponding carboxylic acid (IV) with SOCl2) was then condensed with benzazepine (III) to produce benzamide (VI).Hydrolysis of the methyl ester function of (VI) yielded the racemic carboxylic acid (VII),which was resolved by means of esterification with (R)-2-heptanol,followed by chromatographic separation of the diastereomeric mixture.After saponification of the required diastereoisomeric ester (VIII),the resulting (R)-carboxylic acid was finally coupled with isopropylamine using diethylcyanophosphate as the condensing reagent.
参考文献标题:Characterization of orally active nonpeptide vasopressin V2 receptor agonist.Synthesis and biological evaluation of both the (5R)- and (5S)-enantioisomers of 2-[1-(2-chloro-4-pyrrolidin-1yl-benzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-yl]-N-isopropylace
文献作者:Kondo,K.; Kan,K.W.; Tanada,Y.; Bando,M.; Shinohara,T.; Kurimura,M.; Ogawa,H.; Nakamura,S.; Hirano,T.; Yamamura,Y.; Kido,M.; Mori,T.; Tominaga,M.
参考来源:J Med Chem 2002,45(17),3805
产品链接: CAS No. 192514-54-8››