IQM-97423
Chemical Name: N-[(4aS,5R)-2-Benzyl-1,3-dioxoperhydropyrido[1,2-c]pyrimidin-5-yl]-2(S)-(3-tert-butylureido)-3-(1H-indol-3-yl)propionamide; N1-[(4aS,5R)-2-Benzyl-1,3-dioxoperhydropyrido[1,2-c]pyrimidin-5-yl]-N2-(N-tert-butylcarbamoyl)-L-tryptophanamide
CAS No. 251361-82-7
项目整合开发状态: Preclinical
项目研究机构: CSIC (Originator), Universidad de Navarra (Originator)
合成路线:Condensation of Boc-D-Orn(COOCH2Ph)-OH (I) with the lithium salt of ethyl acetate (A) in the presence of CDI in THF affords derivative (II),which is then hydrogenated over Pd/C to yield the mixture of isomers (IIIa-b).Condensation of (IIIa-b) with benzyl isocyanate in THF,followed by simultaneous reduction and cyclization by means of NaH in THF,provides 1,3-dioxoperhydropyrido[1,2-c]pyrimidine (Va-b),whose N-Boc group is removed by treatment with TFA in CH2Cl2 to furnish amine (VI).Coupling of (VIa-b) to Boc-L-Trp-OH (VII) by means of BOP and Et3N in CH2Cl2,followed by chromatographic separation,gives derivative (VIII),which is subjected to Boc removal by treatment with TFA in CH2Cl2 to provide amine (IX).Finally,amine (IX) is condensed with t-butyl isocyanate in the presence of Et3N in THF to yield the target compound.
📌 参考资料/链接：
参考文献标题:Synthesis and stereochemical structure-activity relationships of 1,3-dioxoperhydropyrido[1,2-c]pyrimidine derivatives: Potent and selective cholecystokinin-A receptor antagonists
文献作者:Mart韓-Mart韓ez,M.; Bartolome-Nebreda,J.M.; Gomez-Monterrey,I.; Gonzalez-Muniz,R.; Garcia-Lopez,M.T.; Ballaz,S.; Barber,A.; Fortuno,A.; del Rio,J.; Herranz,R.
参考来源:J Med Chem 1997,40(21),3402
📄 详细内容
合成路线:Condensation of Boc-D-Orn(COOCH2Ph)-OH (I) with the lithium salt of ethyl acetate (A) in the presence of CDI in THF affords derivative (II),which is then hydrogenated over Pd/C to yield the mixture of isomers (IIIa-b).Condensation of (IIIa-b) with benzyl isocyanate in THF,followed by simultaneous reduction and cyclization by means of NaH in THF,provides 1,3-dioxoperhydropyrido[1,2-c]pyrimidine (Va-b),whose N-Boc group is removed by treatment with TFA in CH2Cl2 to furnish amine (VI).Coupling of (VIa-b) to Boc-L-Trp-OH (VII) by means of BOP and Et3N in CH2Cl2,followed by chromatographic separation,gives derivative (VIII),which is subjected to Boc removal by treatment with TFA in CH2Cl2 to provide amine (IX).Finally,amine (IX) is condensed with t-butyl isocyanate in the presence of Et3N in THF to yield the target compound.
参考文献标题:5-(Tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based potent and selective CCK1 receptor antagonists: Structural modifications at the tryptophan domain
文献作者:Bartolom?Nebreda,J.M.; G髆ez-Monterrey,I.; Garc韆-L髉ez,M.T.; Gonz醠ez-Mu駃z,R.; Mart韓-Martinez,M.; Ballaz,S.; Cenarruzabeitia,E.; LaTorre,M.; Del Rio,J.; Herranz,R.
参考来源:J Med Chem 1999,42(22),4659