TY - JOUR
T1 - Solid-phase synthesis of 2-substituted 4-amino-7-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidines
AU - Falcó, José L.
AU - Borrell, José I.
AU - Teixidó, Jordi
PY - 2003
Y1 - 2003
N2 - 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 α, β-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.
AB - 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 α, β-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.
KW - Knoevenagel reaction
KW - Michael reaction
KW - Pyrido[2,3-d]pyrimidines
KW - Solid-phase synthesis
UR - http://www.scopus.com/inward/record.url?scp=0347719206&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000207215300003&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1023/B:MODI.0000006835.60273.b3
DO - 10.1023/B:MODI.0000006835.60273.b3
M3 - Article
C2 - 14761159
AN - SCOPUS:0347719206
SN - 1381-1991
VL - 6
SP - 85
EP - 92
JO - Molecular Diversity
JF - Molecular Diversity
IS - 2
ER -