Synthesis 2012; 44(20): 3152-3157
DOI: 10.1055/s-0032-1316756
practical synthetic procedures
© Georg Thieme Verlag Stuttgart · New York

Efficient Synthesis of 4-Amino-2-methoxy-7,8-dihydropyrido[4,3-d]pyrimidin-5-ones: Practical Access to a Novel Chemotype in the Development of DGAT-1 Inhibitors

Kevin B. Bahnck*
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Andrei Shavnya
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Yong Tao*
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Susan C. Lilley
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Melissa P. Andrews
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Gary E. Aspnes
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
David J. Bernhardson
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
David R. Bill
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Mark W. Bundesmann
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Robert L. Dow
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Kapil Karki
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Tung Le
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Qifang Li
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Michael J. Munchhof
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Asaad Nematalla
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Mohammed Nihlawi
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Leena Patel
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Christian Perreault
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
,
Michael Waldo
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA, Fax: +1(860)6860605   Email: [email protected]   Email: [email protected]
› Author Affiliations
Further Information

Publication History

Received: 03 March 2012

Accepted after revision: 26 April 2012

Publication Date:
03 July 2012 (online)


Abstract

A practical access to an unprecedented, fused bicyclic 4-amino-2-alkoxy-7,8-dihydropyrido[4,3-d]pyrimidin-5-one scaffold is developed. The synthesis of the potent inhibitor, 2-{4-[4-amino-2-methoxy-5-oxo-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]phenyl}-2-methylpropanamide is detailed, with particular emphasis placed on synthetic efficiency and scalability. With the isolation of solid intermediates, the routes described offer clear elements of practicality and facilitate production of the target compound on large scale (>10 g) without chromatography.

 
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