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【结 构 式】

【药物名称】PD-172803

【化学名称】8-Isopropyl-2-[4-(4-methyl-1-piperazinyl)phenylamino]pyrido[2,3-d]pyrimidin-7(8H)-one

【CA登记号】211245-21-5

【 分 子 式 】C21H26N6O

【 分 子 量 】378.48097

【开发单位】Pfizer (Originator)

【药理作用】Oncolytic Drugs, Cyclin-Dependent Kinase Inhibitors, Inhibitors of Signal Transduction Pathways

合成路线1

Treatment of ethyl 4-chloro-2-(methylsulfanyl)pyrimidine-5-carboxylate (I) with ammonium hydroxide provided the aminopyrimidine (II). After reduction of the ethyl ester (II) to alcohol (III) with LiAlH4, oxidation with MnO2 in chloroform yielded aldehyde (IV). Wittig condensation of (IV) with phosphorane (V) afforded the unsaturated ester (VI), which was cyclized to the pyridopyrimidinone (VII) upon treatment with DBU in diisopropylethylamine. Then, alkylation of (VII) with 2-iodopropane in the presence of NaH in DMF gave rise to the 8-isopropyl pyridopyrimidinone (VIII). Subsequent oxidation of the sulfide group of (VIII) to sulfoxide (X) was carried out employing trans-2-(phenylsulfonyl)-3-phenyloxaziridine (IX). Finally, displacement of the methylsulfinyl group of (X) with 4-(4-methylpiperazin-1-yl)aniline (XI) at 175 C yielded the title compound.

1 Dobrusin, E.M.; Fattacy, A.; Boschelli, D.H.; Fry, D.W.; Wu, Z.; Doherty, A.M.; Kallmeyer, S.T.; Barvian, M.R. (Pfizer Inc.); Pyrido[2,3-d]pyrimidines and 4-aminopyrimidines as inhibitors of cellular proliferation. WO 9833798 .
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) 18198 ethyl 4-chloro-2-(methylsulfanyl)-5-pyrimidinecarboxylate; ETHYL 4-CHLORO-2-METHYLTHIO-5-PYRIMIDINECARBOXYLATE 5909-24-0 C8H9ClN2O2S 详情 详情
(II) 31828 ethyl 4-amino-2-(methylsulfanyl)-5-pyrimidinecarboxylate C8H11N3O2S 详情 详情
(III) 31829 [4-amino-2-(methylsulfanyl)-5-pyrimidinyl]methanol C6H9N3OS 详情 详情
(IV) 31830 4-amino-2-(methylsulfanyl)-5-pyrimidinecarbaldehyde C6H7N3OS 详情 详情
(V) 14182 ethyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate; (Carbethoxymethylene)triphenylphosphorane 1099-45-2 C22H21O2P 详情 详情
(VI) 31831 ethyl (E)-3-[4-amino-2-(methylsulfanyl)-5-pyrimidinyl]-2-propenoate C10H13N3O2S 详情 详情
(VII) 31832 2-(methylsulfanyl)pyrido[2,3-d]pyrimidin-7(8H)-one C8H7N3OS 详情 详情
(VIII) 31833 8-isopropyl-2-(methylsulfanyl)pyrido[2,3-d]pyrimidin-7(8H)-one C11H13N3OS 详情 详情
(IX) 31834 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine;2-(Phenylsulfonyl)-3-phenyloxaziridine;2-Benzenesulfonyl-3-phenyloxaziridine;3-Phenyl-2-phenylsulfonyloxaziridine;3-Phenyl-N-phenylsulfonyloxaziridine;N-(Phenylsulfonyl)phenyloxaziridine;N-Benzenesulfonyl-3-phenyloxaziridine 63160-13-4 C13H11NO3S 详情 详情
(X) 31835 8-isopropyl-2-(methylsulfinyl)pyrido[2,3-d]pyrimidin-7(8H)-one C11H13N3O2S 详情 详情
(XI) 31836 4-(4-methyl-1-piperazinyl)phenylamine; 4-(4-methyl-1-piperazinyl)aniline C11H17N3 详情 详情
Extended Information