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【结 构 式】 
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【分子编号】54374 【品名】2-Methylsulfanylpyrimidin-4-ol; 2-Methylthio-4-hydroxy pyrimidine 【CA登记号】124700-70-5 |
【 分 子 式 】C5H6N2OS 【 分 子 量 】142.18152 【元素组成】C 42.24% H 4.25% N 19.7% O 11.25% S 22.55% |
合成路线1
该中间体在本合成路线中的序号：(I)The synthesis can be performed by two related ways: 1) The condensation of 2-(methylsulfanyl)pyrimidin-4-ol (I) with 4-aminobenzonitrile (II) in hot diglyme gives 4-(4-hydroxypyrimidin-2-ylamino)benzonitrile (III), which is treated with POCl3 to yield the corresponding chloro derivative (IV). Finally, this compound is condensed with 2,4,6-trimethylaniline (V) in dioxane to afford the target 4-aminobenzonitrile derivative. 2) Condensation of 2,4,6-trimethylaniline (VI) with 2,4-dichloropyrimidine (VII) by means of DIEA in refluxing 1,4-dioxane, followed by chromatographic purification furnishes intermediate (VIII), which is finally converted into the desired compound by condensation with 4-aminobenzonitrile (II) in refluxing water by means of HCl in 2-propanol.
| 【2】 Heeres, J.; Kukla, M.J.; Andries, K.J.L.M.; Janssen, P.A.J.; Ho, C.Y.; Janssen, M.A.C.; Ludovici, D.W.; de Corte, B.; de Jonge, M.R.; Koymans, L.M.H.; van Aken, K.J.A. (Janssen Pharmaceutica NV); HIV inhibiting pyrimidine derivs.. EP 0945442; EP 0945443; US 6197779; US 6440986; WO 9950250 . |
| 【1】 Ludovici, D.W.; De Corte, B.L.; Kukla, M.J.; et al.; Evolution of anti-HIV drug candidates. Part 3: Diarylpyrimidine (DAPY) analogues. Bioorg Med Chem Lett 2001, 11, 17, 2235. |
| 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) | 54374 | 2-Methylsulfanylpyrimidin-4-ol; 2-Methylthio-4-hydroxy pyrimidine | 124700-70-5 | C5H6N2OS | 详情 | 详情 |
| (II) | 15361 | 4-Aminobenzonitrile | 873-74-5 | C7H6N2 | 详情 | 详情 |
| (III) | 54375 | 4-[(4-hydroxy-2-pyrimidinyl)amino]benzonitrile; 4-[(1,4-Dihydro-4-oxo-2-pyrimidinyl)amino]benzonitrile | 189956-45-4 | C11H8N4O | 详情 | 详情 |
| (IV) | 54376 | 4-[(4-chloro-2-pyrimidinyl)amino]benzonitrile | 244768-32-9 | C11H7ClN4 | 详情 | 详情 |
| (V) | 28804 | 2,4,6-trimethylaniline | 88-05-1 | C9H13N | 详情 | 详情 |
| (VII) | 54377 | 2,4-Dichloropyrimidine | 3934-20-1 | C4H2Cl2N2 | 详情 | 详情 |
| (VIII) | 54378 | 2-chloro-N-mesityl-4-pyrimidinamine; N-(2-chloro-4-pyrimidinyl)-N-mesitylamine | C13H14ClN3 | 详情 | 详情 |