利用α-甲基苄基树脂将伯胺环化至哌嗪和二氮杂螺环化合物上。

Annulation of primary amines to piperazines and diazaspirocycles utilizing alpha-methyl benzyl resin.

作者信息

Macleod Calum, Martinez-Teipel Blanca I, Barker William M, Dolle Roland E

机构信息

Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, Pennsylvania 19341, USA.

出版信息

J Comb Chem. 2006 Jan-Feb;8(1):132-40. doi: 10.1021/cc050106w.

DOI:10.1021/cc050106w

PMID:16398564

Abstract

The microwave-assisted solid-phase synthesis of piperazines, 3,9-diazaspiro[5.5]undecanes and 2,9-diazaspiro[5.5]undecanes is reported. The synthesis relies on the direct annulation of primary amines with resin-bound bismesylates. Critical to the success of this chemistry was the development of alpha-methyl benzyl carbamate resin linker. This resin permits the cleavage of the heterocycles under mildly acidic conditions, free of contaminating linker-derived N-alkylated byproducts.

摘要

报道了哌嗪、3,9-二氮杂螺[5.5]十一烷和2,9-二氮杂螺[5.5]十一烷的微波辅助固相合成。该合成依赖于伯胺与树脂结合的双甲磺酸酯的直接环化反应。这种化学方法成功的关键在于α-甲基苄基氨基甲酸酯树脂连接基的开发。这种树脂能够在温和酸性条件下裂解杂环，且不会产生污染性的连接基衍生的N-烷基化副产物。