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A Novel and Efficient Approach for the Combinatorial Synthesis of Structurally Diverse Pyrimidines on solid support
Author(s) -
Obrecht Daniel,
Abrecht Christine,
Grieder Alfred,
Villalgordo José M.
Publication year - 1997
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19970800106
Subject(s) - chemistry , combinatorial chemistry , solid phase synthesis , combinatorial synthesis , nanotechnology , stereochemistry , biochemistry , peptide , materials science
We describe a versatile novel approach for the synthesis of 2, 4, 6‐trisubstituted pyrimidines on solid support. Thus, polymer‐boun J thiouronium salt 2 reacted in high yield in a cyclocondensation reaction with the acetylenic ketones 3 to form, after tert ‐butyl‐ester cleavage, the polymer‐bound carboxylic acids 4 , which were cleaved by oxidation with 3‐chloroperbenzoic acid and pyrrolidine to form the 2‐pyrrolidinylpyrimidine‐4‐carboxylic acids 6a‐c in high yields and purities without further purification ( Scheme 1 ). Alternatively, acid 4a was subjected to an Ugi four‐component condensation which gave the polymer‐bound Ugi products 9a‐e in good yields ( Scheme 2 ). Multidirectional cleavage reaction of sulfone 8a with different nucleophiles resulted in the clean formation of pyrimidine‐4‐carboxamides 10–13 ( Scheme 3 ). This strategy combines efficiently solid‐phase chemistry with a multicomponent reaction and a multidirectional cleavage step to form highly diverse pyrimidines in a parallel array.