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【结 构 式】 
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【分子编号】64075 【品名】2-methyl-4,6-bis(trichloromethyl)-1,3,5-triazine 【CA登记号】 |
【 分 子 式 】C6H3Cl6N3 【 分 子 量 】329.82624 【元素组成】C 21.85% H 0.92% Cl 64.49% N 12.74% |
合成路线1
该中间体在本合成路线中的序号：(XIX)Pyrimidinone (X) is treated with trifluoromethanesulfonic anhydride and Et3N to provide the pyrimidinyl triflate (XV). The triflate group of (XV) is subsequently displaced with cis-1-benzyl-3,5-dimethylpiperazine (XVI) to generate the pyrimidinyl piperazine adduct as a diastereomeric mixture, from which isomer (XVII) can be isolated as the corresponding L-dibenzoyltartrate salt. Removal of the N-benzyl protecting group of (XVII) by transfer hydrogenolysis leads to piperazine (XVIII) (1). This is then coupled with 2-methyl-4,6-bis(trichloromethyl)-[1,3,5]triazine (XIX) to furnish (XX). Finally, dechlorination of (XX) by hydrogenation over Pd/C, followed by acidic ester hydrolysis gives rise to the title compound (1,2).
| 【1】 Mylari, B.L.; Oates, P.J.; Zembrowski, W.J.; Beebe, D.A.; Conn, E.L.; Coutcher, J.B.; O'Gorman, M.T.; Linhares, M.C,; Withbroe, G.J.; A sorbitol dehydrogenase inhibitor of exceptional in vivo potency with a long duration of action: 1-(R)-[4-[4-(4,6-Dimethyl[1,3,5]triazin-2-yl)-2R,6S-dimethylpiperazin-1-yl]pyrimidin-2-yl]ethanol. J Med Chem 2002, 45, 20, 4398. |
| 【2】 Mylari, B.L.; Zembrowski, W.J.; Murry, J.A.; Chu-Moyer, M.Y. (Pfizer Products Inc.); Aminopyrimidines as sorbitol dehydrogenase inhibitors. EP 1185275; US 6414149; WO 0059510 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 64066 | (1R)-1-(6-oxo-1,6-dihydro-2-pyrimidinyl)ethyl butyrate | C10H14N2O3 | 详情 | 详情 | |
| (XV) | 64071 | (1R)-1-(4-{[(trifluoromethyl)sulfonyl]oxy}-2-pyrimidinyl)ethyl butyrate | C11H13F3N2O5S | 详情 | 详情 | |
| (XVI) | 64072 | (3R,5S)-1-benzyl-3,5-dimethylpiperazine | C13H20N2 | 详情 | 详情 | |
| (XVII) | 64073 | C41H46N4O10 | 详情 | 详情 | ||
| (XVIII) | 64074 | C34H40N4O10 | 详情 | 详情 | ||
| (XIX) | 64075 | 2-methyl-4,6-bis(trichloromethyl)-1,3,5-triazine | C6H3Cl6N3 | 详情 | 详情 | |
| (XX) | 64076 | (1R)-1-(4-{(2R,6S)-2,6-dimethyl-4-[4-methyl-6-(trichloromethyl)-1,3,5-triazin-2-yl]piperazinyl}-2-pyrimidinyl)ethyl butyrate | C21H28Cl3N7O2 | 详情 | 详情 |