Solid-phase synthesis of 2-substituted 4-amino-7-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidines: An example of cyclization-assisted cleavage |
| |
Authors: | Falcó José L Matallana Josep L Barberena Jaume Teixidó Jordi Borrell José I |
| |
Institution: | (1) Grup d'Enginyeria Molecular, Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona, Spain;(2) Grup d'Enginyeria Molecular, Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona, Spain |
| |
Abstract: | An efficient solid-phase synthesis of 2-substituted 4-aminopyrido2,3-d]pyrimidines 12 by cyclization-assisted cleavage from resin is reported. The procedure starts by solid supporting an , -unsaturated acid 8 to the Wang resin 13 by using DCC and 4-DMAP in THF. The resulting , -unsaturated ester 14 is converted to the Michael adduct by treatment with malononitrile in NaOMe/THF. Such Michael addition constitutes the first example of a Michael reaction with malononitrile in solid-phase. Finally, the Michael adducts 15 are treated with an amidine system in MeOH to yield the corresponding pyridopyrimidines 12. Compounds 12 present three diversity centers R1, R2 and G. Having validated the chemistry on solid support, a 40-membered combinatorial library was obtained using this protocol. |
| |
Keywords: | combinatorial library cyclization-assisted cleavage Michael reaction pyrido[2 3-d]pyrimidines solid-phase synthesis |
本文献已被 PubMed SpringerLink 等数据库收录! |
|