General scope of 1,4-diastereoselective additions to a 2(3H)-quinazolinone:: Practical preparation of HIV therapeutics

被引：42

作者：

Magnus, NA ^{[1
]}

Confalone, PN ^{[1
]}

Storace, L ^{[1
]}

Patel, M ^{[1
]}

Wood, CC ^{[1
]}

Davis, WP ^{[1
]}

Parsons, RL ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Chem Proc Res & Dev Dept, Pharmaceut Res Inst, Deepwater, NJ 08023 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2003年 / 68卷 / 03期

关键词：

D O I：

10.1021/jo0263162

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The practical and highly diastereoselective syntheses of CF3-substituted dihydroquinazolinones via 1,4-additions of nucleophiles to chiral auxiliary substituted 2(3H)-quinazolinones is described. This methodology is applied to the syntheses of the NNRTIs (nonnucleoside reverse transcriptase inhibitors) DPC 961 (1) and DPC 083 (2), which are useful for the treatment of HIV (human immunodeficiency virus). The synthesis of DPC 961 (1) requires three steps, proceeds in >55% overall yield from the keto-aniline 9, and gives synthetic access to DPC 083 (2). In addition, the scope of the new diastereoselective 1,4-addition chemistry is investigated. The first preparation of DPC 961 (1) described in this paper is a derivatization fractional crystallization protocol.

引用

页码：754 / 761

页数：8

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