LY-335738

Chemical Name: 2-[5-[2-(2,4-Diamino-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl)ethyl]furan-2-ylcarbonyl]-L-glutamic acid
项目整合开发状态: Biological Testing
项目研究机构: Lilly (Originator)
合成路线:Pyridopyrimidinone (I) was condensed with triazole (II) in the presence of 4-chlorophenyl dichlorophosphate and pyridine to afford (III).Further reaction of (III) with ammonia in dioxan gave amino compound (IV),which was submitted to a Heck reaction with 4-iodobenzoyl-L-glutamic acid diethyl ester (V) in the presence of palladium catalyst and CuI to provide the disubstituted acetylene (VI).Hydrogenation of both acetylene group and pyridine ring of (VI) over Pd/C gave intermediate (VII).The amide and ester groups of (VII) were finally hydrolyzed with 1 N NaOH to furnish the title compound.

合成路线:Pyridopyrimidinone (I) was condensed with triazole (II) in the presence of 4-chlorophenyl dichlorophosphate and pyridine to afford (III).Further reaction of (III) with ammonia in dioxan gave amino compound (IV),which was submitted to a Heck reaction with N-(2-bromothien-5-yl)-L-glutamic acid diethyl ester (V) in the presence of palladium catalyst and CuI to provide the disubstituted acetylene (VI).Hydrogenation of both acetylene group and pyridine ring of (VI) over Pd/C gave intermediate (VII).The amide and ester groups of (VII) were finally hydrolyzed with 1 N NaOH to furnish the title compound.

合成路线:Pyridopyrimidinone (I) was condensed with triazole (II) in the presence of 4-chlorophenyl dichlorophosphate and pyridine to afford (III).Further reaction of (III) with ammonia in dioxan gave amino compound (IV),which was submitted to a Heck reaction with N-(2-bromofuran-5-yl)-L-glutamic acid diethyl ester (V) in the presence of palladium catalyst and CuI to provide the disubstituted acetylene (VI).Hydrogenation of both acetylene group and pyridine ring of (VI) over Pd/C gave intermediate (VII).The amide and ester groups of (VII) were finally hydrolyzed with 1 N NaOH to furnish the title compound.