Solid-phase synthesis of 2-substituted 4-amino-7-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidines.
An efficient solid-phase synthesis of 2-substituted 4-aminopyrido[2,3-d]pyrimidines 15 is reported. The procedure started by solid supporting a p-hydroxybenzaldehyde 8 to the Wang resin by using the Mitsunobu protocol. The resulting aldehyde 17 was treated with a substituted acid methyl malonate 10 to afford the corresponding alpha, beta-unsaturated ester 18, which was converted to the Michael adduct 21 by reaction with malononitrile. Cyclization of 21 with an amidine system 13 yielded the solid supported pyridopyrimidine 22, which afforded the corresponding 2-substituted 4-aminopyrido[2,3-d]pyrimidine 15 upon treatment with TFA:DCM. Compounds 15 present three diversity centers R1, R2 and R3. Having validated the chemistry on solid support, a 32-membered combinatorial library was obtained using this protocol.
Falcó
José L
JL
Grup d'Enginyeria Molecular, Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona, Spain.
Borrell
José I
JI
Teixidó
Jordi
J
D020650:Combinatorial Chemistry Techniques; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry
D011728:Pyridones; D011743:Pyrimidines