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【结 构 式】 
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【分子编号】31830 【品名】4-amino-2-(methylsulfanyl)-5-pyrimidinecarbaldehyde 【CA登记号】 |
【 分 子 式 】C6H7N3OS 【 分 子 量 】169.2072 【元素组成】C 42.59% H 4.17% N 24.83% O 9.46% S 18.95% |
合成路线1
该中间体在本合成路线中的序号：(IV)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 |