diethyl (2S)-2-([[5-(2-[4-amino-2-[(2,2-dimethylpropanoyl)amino]-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl]ethyl)-2-thienyl]carbonyl]amino)pentanedioate -Drug Synthesis Database

【结构式】

【分子编号】23139

【品名】diethyl (2S)-2-([[5-(2-[4-amino-2-[(2,2-dimethylpropanoyl)amino]-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl]ethyl)-2-thienyl]carbonyl]amino)pentanedioate

【CA登记号】

【分子式】C₂₈H₄₀N₆O₆S

【分子量】588.72844

【元素组成】C 57.12% H 6.85% N 14.27% O 16.31% S 5.45%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(VII)

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.

参考文献中间体

合成目标

【1】 Gossett, L.S.; Habeck, L.L.; Shackelford, K.A.; Mendelsohn, L.G.; Gates, S.B.; Worzalla, J.F.; Self, T.D.; Theobald, K.S.; Andis, S.L.; Schultz, R.M.; Shih, C.; The synthesis and biological activity of a series of 2,4-diaminopyrido[2,3-d]pyrimidine based antifolates as antineoplastic and antiarthritic agents. Bioorg Med Chem Lett 1999, 9, 1, 75.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	14282	N-(6-Ethynyl-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropanamide		C₁₄H₁₄N₄O₂	详情	详情
(II)	13135	1H-1,2,4-Triazole; 1,2,4-Triazole	288-88-0	C₂H₃N₃	详情	详情
(III)	23132	N-[6-ethynyl-4-(1H-1,2,4-triazol-1-yl)pyrido[2,3-d]pyrimidin-2-yl]-2,2-dimethylpropanamide		C₁₆H₁₅N₇O	详情	详情
(IV)	23133	N-(4-amino-6-ethynylpyrido[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropanamide		C₁₄H₁₅N₅O	详情	详情
(V)	23137	diethyl (2S)-2-[[(5-bromo-2-thienyl)carbonyl]amino]pentanedioate		C₁₄H₁₈BrNO₅S	详情	详情
(VI)	23138	diethyl (2S)-2-([[5-(2-[4-amino-2-[(2,2-dimethylpropanoyl)amino]pyrido[2,3-d]pyrimidin-6-yl]ethynyl)-2-thienyl]carbonyl]amino)pentanedioate		C₂₈H₃₂N₆O₆S	详情	详情
(VII)	23139	diethyl (2S)-2-([[5-(2-[4-amino-2-[(2,2-dimethylpropanoyl)amino]-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl]ethyl)-2-thienyl]carbonyl]amino)pentanedioate		C₂₈H₄₀N₆O₆S	详情	详情

Extended Information