An efficient solid-phase synthesis of 2-alkyl-4,6-diaminopyrimidines and 2,4,6-triaminopyrimidines

• Published in: Tetrahedron Vol. 62; no. 10; pp. 2304 - 2312
• Main Authors: Wéber, Csaba, Demeter, Ádám, Greiner, István
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 06.03.2006; Elsevier
• Subjects: 4,6-Dichloropyrimidines; Aliphatic amines; Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; Solid-phase; DIEA; Pyr; Pip-C(2,6); 4,6-Dichloropyrimidines; DMAC; Pip-H(2,6); eq; TFA; DCM; TEA; x H and y H; THF; Solid-phase; m-CPBA; Pip; ax; DMF; Aliphatic amines; PYRIMIDINE RING; 2,4,6-TRICHLOROPYRIMIDINE; 2,4-DIAMINOPYRIMIDINES; aliphatic amines; 4,6-dichloropyrimidines; AGENTS; solid-phase; PROTONATION
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2005.12.004

An efficient and simple approach for the solid-phase synthesis of 2,4,6-triaminopyrimidines and 2-alkyl-4,6-diaminopyrimidines is described. Primary amines were immobilized on 2-(4-formyl-3-methoxyphenoxy)ethyl polystyrene resin via reductive amination. Attachment of two different 4,6-dichloropyrimidines led to the corresponding 4-chloro-6-aminopyrimidine intermediates. Aromatic nucleophilic substitution with various aliphatic amines or the corresponding lithium amides afforded the desired aminopyrimidines in high yield and excellent purity after acidic cleavage from the resin. The products were characterized by LC–MS, 1H and 13C NMR spectroscopy. Deuterium exchange experiments revealed that the investigated aminopyrimidines have a general tendency toward C-5 protonation. Graphical Abstract