247565-03-3

Usage

Uses

Used in Pharmaceutical Industry:
2(1H)-Quinazolinone, 6-chloro-3,4-dihydro-4-hydroxy-3-[(1R)-1-phenylethyl]-4-(trifluoromethyl)-, (4S)is used as an intermediate in the synthesis of HIV non-nucleoside reverse transcriptase inhibitors, specifically for the compound DPC 961 (D585800). Its unique structure plays a crucial role in the development of this class of antiretroviral drugs, which are essential in the treatment of HIV/AIDS.

Upstream product

• 33375-06-3 (1R)-1-phenylethyl isocyanate 
• 214353-17-0 4-chloro-2-trifluoroacetylaniline hydrochloride hydrate 

Downstream Products

• 497235-43-5 3-((1R)-1-phenylethyl)-6-chloro-4-(trifluoromethyl)-3-hydroquinazolin-2-one 

Relevant academic research and scientific papers

Process development challenges to accommodate a late-appearing stable polymorph: A case study on the polymorphism and crystallization of a fast-track drug development compound

The case of disappearing/late-appearing stable polymorphs and their impact is well-understood by scientists in the pharmaceutical industry. This paper discusses an instance where a more stable crystal form was discovered during the development of a fast-track drug candidate. Challenges in adapting to the discovery of the new crystal form during this accelerated drug development program and approaches to develop a robust crystallization process are discussed.

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

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.

A new asymmetric 1,4-addition method: Application to the synthesis of the HIV non-nucleoside reverse transcriptase inhibitor DPC 961

The asymmetric synthesis of the HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) DPC 961 is achieved in three steps with an overall yield of >55%. The asymmetry is induced by the chiral auxiliary (R)-(+)-α- methylbenzylamine, utilizing a new asymmetric 1,4-addition protocol. (C) 2000 DuPont Pharmaceuticals Company. Published by Elsevier Science Ltd.