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Synthesis 2011(10): 1529-1531  
DOI: 10.1055/s-0030-1259976
SHORTPAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Scalable Synthesis of 4-Substituted 5-Bromo-6-methylpyrimidines

Zhihan Wanga, Yushi Chia, Anthony R. Harrisb, David Grayb, Jennifer E. Davoren*b
a WuXi AppTec, Fute Zhong Road, Pudong New District, Shanghai 200131, P. R. of China
b Neurosciences Chemistry, Pfizer Global Research and Development, Groton, CT 06340, USA
Fax: +1(860)6867444; e-Mail: jennifer.e.davoren@pfizer.com;
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Publication History

Received 3 February 2011
Publication Date:
31 March 2011 (online)

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Abstract

Small halogenated heteroaromatic ring systems are valuable monomers, which can enable rapid access to novel and desirable chemical space, in part because of their ability to participate in established cross coupling chemistry such as the Heck, Stille, and Suzuki reactions. Described is a practical, scalable synthetic route towards the construction of a diverse array of 4-substituted 5-bromo-6-methylpyrimidine monomers.

Key words

heterocycle - heteroaromatic ring - pyrimidine - library monomer

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4

Yields as high as 95% are consistently obtained on a five-gram scale.

10

Significant quantities of highly soluble 5-bromo-4-(bromo-methyl)-6-methylpyrimidine and an unidentified tribro-minated product were detected in the mother liquor by NMR and LCMS analyses.

11

Three steps from 5-bromo-4,6-dimethylpyrimidin-2-ol.