Regioselective Construction and Screening of 1,3-Disubstituted Tetrahydroindazolones in Enantiomerically Pure Pairs
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- 作者：Heebum Song ; Hanjae Lee ; Jonghoon Kim ; Seung Bum Park
- 刊名：ACS Combinatorial Science
- 出版年：2012
- 出版时间：January 9, 2012
- 年：2012
- 卷：14
- 期：1
- 页码：66-74
- 全文大小：522K
- 年卷期：v.14,no.1(January 9, 2012)
- ISSN：2156-8944
文摘
In this paper, we describe a regioselective synthetic pathway for enantiopure 1,3-disubstituted tetrahydroindazolone derivatives via the condensation of 2-acylcyclohexane-1,3-dione with various alkyl- and arylhydrazines using the steric effects of a Boc-protected pyrrolidine ring. This synthetic method has a broad scope for substrate generality for various hydrazines with excellent regioselectivity. To maximize the molecular diversity, further diversifications of 1,3-disubstituted tetrahydroindazolones were pursued by systematic N-modification of the secondary amine of the pyrrolidine ring using solution-phase parallel synthesis with polymer-supported reagents. A library containing a total of 272 drug-like tetrahydroindazolones, including 85 enantiomeric pairs, was constructed; the average purity, without further purification, was 95%.