Pelitrexol, AG-2037, AG-2038((6R)-isomer), AG-2032(racemate)

N-((5-(2-((6S)-2-氨基-1,4,5,6,7,8-六氢-4-氧代吡啶并[2,3-D]嘧啶-6-基)乙基)-4-甲基-2-噻吩)甲酰基)-L-谷氨酸Chemical Name: N-[5-[2-[2-Amino-4-oxo-3,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidin-6(S)-yl]ethyl]-4-methylthien-2-ylcarbonyl]-L-glutamic acid
CAS No. 446022-33-9, 177587-08-5 (racemate)
项目整合开发状态: Phase I
项目研究机构: Pfizer (Originator)
合成路线:Acylation of diethyl L-glutamate (I) with 5-bromo-4-methylthiophene-2-carboxylic acid (II) using EDC as the coupling reagent provided amide (III).Subsequent palladium-catalyzed coupling between bromothiophene (III) and ethynyl pyridopyrimidinone (IV) furnished the disubstituted acetylene (V),which was further hydrogenated to (VI) in the presence of Pd/C in trifluoroacetic acid.Finally,basic hydrolysis of the ethyl ester and pivaloyl groups of (VI) led to the title compound.