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【结 构 式】 
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【药物名称】RS-127445 【化学名称】4-(4-Fluoro-1-naphthyl)-6-isopropylpyrimidin-2-amine 【CA登记号】199864-87-4, 199864-86-3 (mono HCl salt) 【 分 子 式 】C17H16FN3 【 分 子 量 】281.33557 |
【开发单位】Roche Bioscience (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Antimigraine Drugs, 5-HT2B Antagonists |
合成路线1
Cyclization of ethyl 4-methyl-3-oxopentanoate (I) with guanidine carbonate (II) in boiling EtOH gave 2-amino-4-hydroxy-6-isopropylpyrimidine (III), which was converted to the corresponding chloropyrimidine (IV) by means of POCl3. Boronic ester (VI) was prepared by lithiation of 1-bromo-4-fluoronaphthalene (V) with n-butyllithium, followed by reaction with trimethyl borate. Subsequent coupling of chloropyrimidine (IV) with boronic ester (VI) in the presence of tetrakis(triphenylphosphine)palladium yielded the target naphthylpyrimidine.
| 【1】 Berger, J.; Flippin, L.A.; Greenhouse, R.; Jaime-Figueroa, S.; Liu, Y.; Miller, A.K.; Putman, D.G.; Weinhardt, K.K.; Zhao, S.-H. (F. Hoffmann-La Roche AG); Aryl pyrimidine derivs.. EP 0901474; US 5863924; WO 9744326 . |
| 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) | 19408 | ethyl 4-methyl-3-oxopentanoate | 7152-15-0 | C8H14O3 | 详情 | 详情 |
| (II) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |
| (III) | 30387 | 2-amino-6-isopropyl-4-pyrimidinol | C7H11N3O | 详情 | 详情 | |
| (IV) | 30388 | 4-chloro-6-isopropyl-2-pyrimidinylamine; 4-chloro-6-isopropyl-2-pyrimidinamine | C7H10ClN3 | 详情 | 详情 | |
| (V) | 30389 | 1-bromo-4-fluoronaphthalene | 341-41-3 | C10H6BrF | 详情 | 详情 |
| (VI) | 30390 | dimethyl 4-fluoro-1-naphthylboronate | C12H12BFO2 | 详情 | 详情 |