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Synthesis and exchange reactions of 5‐alkyl‐2‐oxo‐6‐thioxo‐1,2,3,6‐hexahydropyrimidine‐4‐carboxylic acids
Author(s) -
Batty Craig A.,
Manthey Michael K.,
Kirk Julie,
Manthey Monika,
Christopherson Richard I.,
Hambley Trevor
Publication year - 1997
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.5570340444
Subject(s) - chemistry , alkyl , reagent , carboxylic acid , acetic acid , zinc , organic chemistry , derivative (finance) , medicinal chemistry , economics , financial economics
Abstract An improved preparation of 2‐oxo‐6‐thioxo‐1,2,3,6‐hexahydropyrimidine‐4‐carboxylic acid 3, a potent inhibitor of dihydroorotase is presented. Trans ‐5‐alkyl‐2‐oxo‐6‐thioxohexahydropyrimidine‐4‐carboxylic acids 12a‐c were synthesised via the thiation of the p ‐methoxybenzyl esters of 5‐alkyldihydroorotic acids with Lawesson's reagent followed by subsequent de‐protection. The corresponding cis isomers were prepared by reduction of 5‐alkyl‐6‐thioxoorotic acids with zinc in acetic acid. The stability and exchange reactions of 12a‐c under physiological conditions were investigated by ultra‐violet and 1 H nmr spectroscopy. The attempted synthesis of 16 , a fused cyclopentyl derivative of 3 is also presented.