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Synthesis of 2,4‐diamino‐5,10‐dideaza nonclassical antifolates
Author(s) -
Gangjee Aleem,
Devraj Rajesh,
Lin FuTyan
Publication year - 1991
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570280717
Subject(s) - chemistry , dihydrofolate reductase , pyrimidine , catalysis , derivative (finance) , palladium , stereochemistry , catalytic hydrogenation , amidine , condensation , medicinal chemistry , combinatorial chemistry , organic chemistry , enzyme , financial economics , economics , physics , thermodynamics
Condensation of 2,4,6‐triaminopyrimidine ( 8 ) with bromomalonaldehyde ( 9 ) afforded, after pivaloylation, 2,4‐dipivaloyl‐6‐bromopyrido[2,3‐ d ]pyrimidine ( 11 ). This 6‐bromo derivative served as a key intermediate for the synthesis of 2,4‐diamino‐6‐[2‐(3′,4′‐dimethoxyphenyl)ethenyl]pyrido[2,3‐ d ]pyrimidine ( 5 ) via a palladium catalyzed carbon‐carbon coupling with 3,4‐dimethoxystyrene ( 12 ). Compound 5 , its 9,10‐dihydro analogue 6 and the 5,6,7,8,9,10‐hexahydro analogue 7 were of interest as potential inhibitors of dihydrofolate reductase. Compounds 6 and 7 were synthesized from 5 by catalytic hydrogenation over 5% Pd‐C.