Abstract

A practical synthesis of (S)-tert-butyl 3-methyl-1,4-di­azepane-1-carboxylate has been established for supplying this key intermediate of Rho–kinase inhibitor K-115 in a multikilogram production. The chiral 1,4-diazepane was constructed by intramolecular Fukuyama–Mitsunobu cyclization of a N-nosyl diamino alcohol starting from the commercially available (S)- or (R)-2-aminopropan-1-ol. In the same manner, an enantiomeric pair of a structural isomer were prepared for demonstration of the synthetic utility.

A practical synthesis of (S)-tert-butyl 3-methyl-1,4-di­azepane-1-carboxylate has been established for supplying this key intermediate of Rho–kinase inhibitor K-115 in a multikilogram production. The chiral 1,4-diazepane was constructed by intramolecular Fukuyama–Mitsunobu cyclization of a N-nosyl diamino alcohol starting from the commercially available (S)- or (R)-2-aminopropan-1-ol. In the same manner, an enantiomeric pair of a structural isomer were prepared for demonstration of the synthetic utility.

中文翻译：

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实用合成（S）-叔丁基3-甲基-1,4-二氮杂-1-羧酸酯，Rho-激酶抑制剂K-115的关键中间体

摘要

已经建立了实用合成的（S）-3-甲基-1,4-叔二氮-1-羧酸叔丁酯，以多公斤级的产量提供Rho-激酶抑制剂K-115的这一关键中间体。手性1，4-二氮杂e是通过从市售的（S）-或（R）-2-氨基丙-1-醇开始，对N- nosyl二氨基醇进行分子内Fukuyama-Mitsunobu环化而构建的。以相同的方式，制备了结构异构体的对映异构体对以证明合成用途。

已经建立了实用合成的（S）-3-甲基-1,4-叔二氮-1-羧酸叔丁酯，以多公斤级的产量提供Rho-激酶抑制剂K-115的这一关键中间体。手性1，4-二氮杂e是通过从市售的（S）-或（R）-2-氨基丙-1-醇开始，对N- nosyl二氨基醇进行分子内Fukuyama-Mitsunobu环化而构建的。以相同的方式，制备了结构异构体的对映异构体对以证明合成用途。