【结 构 式】 |
【药物名称】202W92, BW-202W92 【化学名称】(-)-6-(Fluoromethyl)-5-(2,3,5-trichlorophenyl)pyrimidine-2,4-diamine 【CA登记号】 【 分 子 式 】C11H8Cl3FN4 【 分 子 量 】321.57061 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】Cerebrovascular Diseases, Treatment of, Ischemic Stroke, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, Sodium Channel Blockers |
合成路线1
2,3,5-Trichlorobenzaldehyde (I) was reduced with NaBH4 to the benzyl alcohol (II) and then converted to the corresponding bromide (III) by means of PBr3 in benzene. Displacement of bromide group of (III) with KCN gave 2,3,5-trichlorophenylacetonitrile (IV), which was condensed with ethyl diethoxyacetate (V) in the presence of NaOEt to provide keto nitrile (VI). Subsequent treatment of (VI) with ethereal diazomethane generated the enol ether (VII). This was cyclized with guanidine (VIII) in boiling EtOH to produce pyrimidine (IX). After ketal hydrolysis of (IX), the resulting aldehyde (X) was reduced with NaBH4 to alcohol (XI). Finally, treatment of (XI) with diethylaminosulfur trifluoride in cold CH2Cl2 provided the desired fluoromethyl compound.
【1】 Miller, A.A.; Nobbs, M.S.; Hyde, R.M.; Leach, M.J. (Glaxo Wellcome plc); Pharmacologically active CNS cpds.. AU 8945964; EP 0372934; EP 0713703; EP 0715851; EP 0727212; EP 0727213; EP 0727214; JP 1990202876; US 5587380; US 5597828; US 5635507; US 5684005 . |
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) | 25670 | 2,3,5-trichlorobenzaldehyde | 56961-75-2 | C7H3Cl3O | 详情 | 详情 |
(II) | 25671 | (2,3,5-trichlorophenyl)methanol | C7H5Cl3O | 详情 | 详情 | |
(III) | 25672 | 1-(bromomethyl)-2,3,5-trichlorobenzene | C7H4BrCl3 | 详情 | 详情 | |
(IV) | 25673 | 2-(2,3,5-trichlorophenyl)acetonitrile | C8H4Cl3N | 详情 | 详情 | |
(V) | 25674 | ethyl 2,2-diethoxyacetate | 6065-82-3 | C8H16O4 | 详情 | 详情 |
(VI) | 25675 | 4,4-diethoxy-3-oxo-2-(2,3,5-trichlorophenyl)butanenitrile | C14H14Cl3NO3 | 详情 | 详情 | |
(VII) | 25676 | (E)-4,4-diethoxy-3-methoxy-2-(2,3,5-trichlorophenyl)-2-butenenitrile | C15H16Cl3NO3 | 详情 | 详情 | |
(VIII) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |
(IX) | 25677 | 2-amino-6-(diethoxymethyl)-5-(2,3,5-trichlorophenyl)-4-pyrimidinylamine | C15H17Cl3N4O2 | 详情 | 详情 | |
(X) | 25678 | 2,6-diamino-5-(2,3,5-trichlorophenyl)-4-pyrimidinecarbaldehyde | C11H7Cl3N4O | 详情 | 详情 | |
(XI) | 25679 | [2,6-diamino-5-(2,3,5-trichlorophenyl)-4-pyrimidinyl]methanol | C11H9Cl3N4O | 详情 | 详情 |