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【结 构 式】 
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【分子编号】68677 【品名】4,6-dichloro-2-(phenylethynyl)pyrimidine 【CA登记号】 |
【 分 子 式 】C12H6Cl2N2 【 分 子 量 】249.099 【元素组成】C 57.86% H 2.43% Cl 28.46% N 11.25% |
合成路线1
该中间体在本合成路线中的序号：(IV)Oxidation of 4,6-dichloro-2-(methylsulfanyl)pyrimidine (I) with 3-chlorobenzoyl peroxide in CH2Cl2 gives the sulfonyl derivative (II), which is alkynylated with phenylacetylenyl magnesium bromide (III) in THF to provide 4,6-dichloro-2-(phenylethynyl)pyrimidine (IV). Condensation of the dichloropyrimidine derivative (IV) with 5-methyl-3-aminopyrazole (V) by means of NaI and DIEA in DMA at 90 °C affords amine (VI), which is coupled with N-methylpiperazine (VII) in the presence of DMAP and DIEA in 1,4-dioxane at 100 °C to furnish the piperazinyl derivative (VIII). Reduction of alkyne (VIII) by means of LiAlH4 in THF gives alkene (IX), which is finally treated with sodium potassium tartrate .
| 【1】 Xiao, X.-Y., Patel, D.V., Ward, J.S., Bray, M.R., Agoston, G.E., Treston, A.M.(Miikana Therapeutics, Inc.). Substituted pyrazole compounds. EP 1928456, JP 2009510107, US 2007142368, WO 2007041358. |
| 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) | 65246 | 4,6-Dichloro-2-(methylthio)pyrimidine；4,6-dichloro-2-(methylsulfanyl)pyrimidine | 6299-25-8 | C5H4Cl2N2S | 详情 | 详情 |
| (II) | 65247 | 4,6-Dichloro-2-(methylsulfonyl)pyrimidine; 2-(Methylsulfonyl)-4,6-Dichloropyrimidine; NSC 45040 | 4489-34-3 | C5H4Cl2N2O2S | 详情 | 详情 |
| (III) | 32758 | bromo(2-phenylethynyl)magnesium；phenylacetylenyl magnesium bromide;(phenylethynyl)magnesium bromide | C8H5BrMg | 详情 | 详情 | |
| (IV) | 68677 | 4,6-dichloro-2-(phenylethynyl)pyrimidine | C12H6Cl2N2 | 详情 | 详情 | |
| (V) | 68679 | 5-methyl-3-aminopyrazole;3-Amino-5-methylpyrazole;3-Methyl-1H-pyrazol-5-amine | 31230-17-8 | C4H7N3 | 详情 | 详情 |
| (VI) | 68678 | 6-chloro-N-(5-methyl-1H-pyrazol-3-yl)-2-(phenylethynyl)pyrimidin-4-amine | C16H12ClN5 | 详情 | 详情 | |
| (VII) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |
| (VIII) | 68680 | N-(5-methyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-(phenylethynyl)pyrimidin-4-amine | C21H23N7 | 详情 | 详情 | |
| (IX) | 68681 | N-(5-methyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-styrylpyrimidin-4-amine;6-(4-Methyl-1-piperazinyl)-N-(5-methyl-1H-pyrazol-3-yl)-2-[(1E)-2-phenylethenyl]-4-pyrimidinamine | 934353-76-1 | C21H25N7 | 详情 | 详情 |