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A Novel Solution‐ and Solid‐Phase Approach to 2,4,5‐tri‐ and 2,4,5,6‐tetrasubstituted pyrimidines and their conversion into condensed heterocycles
Author(s) -
Masquelin Thierry,
Sprenger Daniel,
Baer Roman,
Gerber Fernand,
Mercadal Yves
Publication year - 1998
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.19980810315
Subject(s) - malononitrile , chemistry , nucleophile , alkylation , condensation , cleavage (geology) , combinatorial chemistry , salt (chemistry) , organic chemistry , catalysis , physics , geotechnical engineering , fracture (geology) , engineering , thermodynamics
A novel general synthesis of 2,4,5‐tri‐ and 2,4,5,6‐tetrasubstituted pyrimidines 5a–d and 7a, e, f, g by condensation of thiouronium salts of type 3 with (ethoxymethylidene)malononitrile (4) and [bis(methylthio)methylidene]malononitrile (6) , respectively, was first established in solution ( Scheme 1 ) and successfully transferred onto solid support by using the polymer‐bound thiouronium salt 11 ( Scheme 3 ). Further investigations were directed toward a multidirectional cleavage procedure of the 2‐(alkylsulfinyl) intermediates, obtained from the 2‐(alkylthio)pyrimidines 7a ( Scheme 2 ) or 12 and 14 ( Schemes 3 and 4 ), with different nucleophiles to form highly substituted pyrimidines. In addition, fused‐heterocycle derivatives 22a‐‐h, 24a–c , and 26a–e were generated in good‐to‐excellent yields by condensation of 7a, e, h with versatile isocyanates and isothiocyanates, with subsequent alkylation ( Scheme 5 ).