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Synthesis 2012; 44(20): 3152-3157
DOI: 10.1055/s-0032-1316756
DOI: 10.1055/s-0032-1316756
practical synthetic procedures
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
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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References
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For similar Dieckmann-type condensations en route to five-membered rings, see:
Based on modifications of procedures reported for de novo syntheses of aminopyrimidines, see: