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Synthesis 2012; 44(15): 2396-2400
DOI: 10.1055/s-0031-1290408
paper
© Georg Thieme Verlag Stuttgart · New York

An Efficient Synthesis of 4-Chloro-2-pyrrolino[2,3-d]pyrimidin-6-one and Its 7-Substituted Analogues

Radhe K. Vaid*
Chemical Product Research and Development, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA, Fax: +1(317)2764507   Email: vaid_radhe_k@lilly.com
,
Jeremy T. Spitler
Chemical Product Research and Development, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA, Fax: +1(317)2764507   Email: vaid_radhe_k@lilly.com
,
Sathish Boini
Chemical Product Research and Development, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA, Fax: +1(317)2764507   Email: vaid_radhe_k@lilly.com
,
Scott A. May
Chemical Product Research and Development, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA, Fax: +1(317)2764507   Email: vaid_radhe_k@lilly.com
,
Richard C. Hoying
Chemical Product Research and Development, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA, Fax: +1(317)2764507   Email: vaid_radhe_k@lilly.com
› Author Affiliations
Further Information

Publication History

Received: 11 April 2012

Accepted after revision: 07 May 2012

Publication Date:
18 June 2012 (online)

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Abstract

An efficient synthesis of 4-chloro-2-pyrrolino[2,3-d]pyrimidin-6-one was achieved in four steps starting from dimethyl malonate in 23% overall yield. This synthesis was demonstrated on 100 g scale to obtain 4-chloro-2-pyrrolino[2,3-d]pyrimidin-6-one in 98.5% purity. Similarly, 7-[(2,4-dimethoxyphenyl)methyl]-4-chloro[2,3-d]pyrimidin-6-one and 7-(α-methylbenzyl)-4-chloro[2,3-d]pyrimidin-6-one were synthesized by the reaction of methyl 2-(4,6-dichloropyrimidin-5-yl)acetate with an appropriately substituted benzylamine.

Key words

formamidine acetate - α-methylbenzylamine dimethyl malonate - methyl bromoacetate
 

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