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【结 构 式】 
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【分子编号】50865 【品名】3-(6-fluoro-1,2-benzisoxazol-3-yl)-5-iodopentyl methanesulfonate 【CA登记号】 |
【 分 子 式 】C13H15FINO4S 【 分 子 量 】427.2353132 【元素组成】C 36.55% H 3.54% F 4.45% I 29.7% N 3.28% O 14.98% S 7.51% |
合成路线1
该中间体在本合成路线中的序号：(XI)The condensation of tetrahydropyran-4-carbonyl chloride (V) with refluxing 1,3-difluorobenzene (VI) by means of AlCl3 gives 1-(2,4-difluorophenyl)-1-(tetrahydropyran-4-yl)methanone (VII), which is treated with hydroxylamine hydrochloride and sodium acetate in refluxing ethanol/water to yield the corresponding oxime (VIII). The cyclization of (VIII) by means of KOH in refluxing methanol affords 6-fluoro-3-(tetrahydropyran-4-yl)-1,2-benzisoxazole (IX), which is treated with NaI and Ac-Cl and then with K2CO3 in refluxing acetonitrile to provide the 5-iodopentanol derivative (X). The reaction of the OH group of (X) with Ms-Cl and TEA in dichloromethane gives the corresponding mesylate (XI), which is finally cyclized with the intermediate amine (IV) by means of NaHCO3 in refluxing acetonitrile to yield the target piperidine.
| 【1】 Huguet-Clotet, J.; Marquillas Olondriz, F.; Caldero Ges, J.M.; Del Castillo Nieto, J.C.; Dalmases Barjoan, P.; Bosch Rovira, A. (Vita-Invest, SA); Process for obtaining 3-2-[4-(6-fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]-ethyl-2-methyl-6,7,8,9-tetrahydro-4H-pyrido-[1,2-a]pyrimidine-4-one. ES 2074966 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 50859 | 3-(2-aminoethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one | C11H17N3O | 详情 | 详情 | |
| (V) | 50860 | tetrahydro-2H-pyran-4-carbonyl chloride | 40191-32-0 | C6H9ClO2 | 详情 | 详情 |
| (VI) | 13095 | m-Difluorobenzene; 1,3-Difluorobenzene | 372-18-9 | C6H4F2 | 详情 | 详情 |
| (VII) | 50861 | (2,4-difluorophenyl)(tetrahydro-2H-pyran-4-yl)methanone | C12H12F2O2 | 详情 | 详情 | |
| (VIII) | 50862 | (2,4-difluorophenyl)(tetrahydro-2H-pyran-4-yl)methanone oxime | C12H13F2NO2 | 详情 | 详情 | |
| (IX) | 50863 | 6-fluoro-3-tetrahydro-2H-pyran-4-yl-1,2-benzisoxazole | C12H12FNO2 | 详情 | 详情 | |
| (X) | 50864 | 3-(6-fluoro-1,2-benzisoxazol-3-yl)-5-iodo-1-pentanol | C12H13FINO2 | 详情 | 详情 | |
| (XI) | 50865 | 3-(6-fluoro-1,2-benzisoxazol-3-yl)-5-iodopentyl methanesulfonate | C13H15FINO4S | 详情 | 详情 |