Process development of 4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]aniline dihydrochloride:: A key intermediate for TAK-779, a small-molecule nonpeptide CCR5 antagonist

被引：10

作者：

Hashimoto, H ^{[1
]}

Ikemoto, T ^{[1
]}

Itoh, T ^{[1
]}

Maruyama, L ^{[1
]}

Hanaoka, T ^{[1
]}

Wakimasu, M ^{[1
]}

Mitsudera, H ^{[1
]}

Tomimatsu, K ^{[1
]}

机构：

[1] Takeda Chem Ind Ltd, Chem Dev Labs, Yodogawa Ku, Osaka 5328686, Japan

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2002年 / 6卷 / 01期

关键词：

D O I：

10.1021/op010052o

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A new and efficient synthesis of 4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]aniline dihydrochloride, a key intermediate for the CCR5 antagonist TAK-779, is described. Reductive alkylation of methylamine with tetrahydro-4H-pyran-4-one followed by alkylation of N-methyl-N-(tetrahydropyran-4-yl)amine with 4-nitrobenzylbromide and reduction of N-(4-nitrobenzyl)-N-(tetrahydropyran-4-yl)amine results in a 78% isolated yield from the starting materials by a scalable method, using only commercially available reagents.

引用

页码：70 / 73

页数：4

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