Solid-phase synthesis of a library of 2-diamino-1, 3-thiazole-carboxamides

ORGN 601

Yue H Li, yue.h.li@gsk.com1, Todd L Graybill1, Karen A Evans1, Yonghui Wang1, Jian Jin1, Ralph A Rivero1, Danqi Chen2, Xin Li2, and Jingkang Shen2. (1) High Throughput Chemistry, GlaxoSmithKline, 1250 S. Collegeville Rd, Collegeville, PA 19426, (2) State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institute of Biological Science, 555 Zhuchongzhi Rd, Shanghai, 201203, China
A multi-step, readily automatable solid-phase approach to the synthesis of a diverse and novel 2-diamino-1,3-thiazole-carboxamide library is described. This highly versatile template with four points of diversity was prepared utilizing BAL (Backbone Amide Linker) resin. The sources of diversity are primary amines for the R1 position, custom-synthesized 1,3-thiazoles for the R2 position, symmetrical diamines for the R3 position, and carboxylic acids, acid chlorides, sulfonyl chlorides, aldehydes, or isocyanates for the R4 position. The key step, SNAr (mono-N-arylation), is achieved without cross-linking products and without the use of diamine protecting groups, catalysts, or bases by carefully controlling concentration, equivalents of symmetrical diamines, and reaction temperature. Optimized conditions and results of a small combinatorial array (324 members) synthesized using Irori AccuTag-100 (miniKans) is described.

 

Asymmetric Reactions, Heterocycles, Aromatics, Combinatorial, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 31 August 2005 Washington DC Convention Center -- Hall A, Poster

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005