Regioselective alkylation at the N4 position of a 3-oxo-1,4-benzodiazepine on solid support

被引：12

作者：

Ali, FE ^{[1
]}

Yuan, CCK ^{[1
]}

Ross, ST ^{[1
]}

Hall, LB ^{[1
]}

机构：

[1] SmithKline Beecham Pharmaceut Inc, Dept Med Chem, Div Res & Dev, King Of Prussia, PA 19406 USA

来源：

MOLECULAR DIVERSITY | 2000年 / 5卷 / 01期

关键词：

benzodiazepine; combinatorial array; diversity; Heck reaction; regioselective alkylation; Sasrin (R) resin;

D O I：

10.1023/A:1011377008730

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

An efficient solid phase regioselective alkylation at the N4 position of a 3-oxo-1,4-benzodiazepine template exemplified by 4-H-2,3,4,5-tetrahydro-7-iodo-3-oxo-1H-1,4-benzodiazepine-2-acetate-polymer ester is described. Further chemical elaboration at position 7, utilizing a modified Heck reaction, allows the incorporation of amides from primary or secondary amines. The two diversity points at positions 4 and 7 were utilized to synthesize a 28-membered, combinatorial array on Sasrin (R) resin in moderate yields and > 80% purity. Having validated the chemistry on solid support, a combine and split approach to prepare a bead-bound combinatorial library is achievable utilizing similar experimental practices and procedures as in the array synthesis.

引用

页码：1 / 5

页数：5

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