【结 构 式】 |
【分子编号】15503 【品名】10-methyl-7-[(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]-8,9-dihydropyrido[1,2-a]indol-6(7H)-one 【CA登记号】 |
【 分 子 式 】C37H33N3O 【 分 子 量 】535.68864 【元素组成】C 82.96% H 6.21% N 7.84% O 2.99% |
合成路线1
该中间体在本合成路线中的序号:(VI)The condensation of 10-methyl-6,7,8,9-tetrahydropyrido[1,2-a]indol-6-one (I) with 5-methyl-1-(triphenylmethyl)-1H-imidazole-4-carboxaldehyde (II) by means of BuLi in THF gives 7-[hydroxy[5-methyl-1-(triphenylmethyl)-1H-imidazol-4-yl]methyl]-10-methyl-6,7,8,9-tetrahydropyrido[1,2-a]indol-6-one (III), which is treated with acetic anhydride in pyridine, yielding the corresponding acetoxy derivative (IV). Elimination of acetic acid from (IV) in hot toluene affords the corresponding methylene derivative (V), which is hydrogenated with H2 over Pd/C in DMF/ethanol giving 10-methyl-7-[5-methyl-1-(triphenylmethyl)-1H-imidazol-4-ylmethyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-6-one (VI). Finally, this compound is deprotected in hot acetic acid/water. In order to obtain the (+)-enantiomer, the racemic mixture is treated with either (-)-di-p-toluyl-L-tartaric acid or (+)-di-p-toluyl-D-tartaric acid. The mixture of diastereomeric salts is separated by fractional crystallization. The pure (+)-enantiomer is obtained by treatment of the corresponding tartrate salt with NaHCO3 or NaOH in water. Finally, the (+)-free base is treated with HCl in methanol.
【1】 Kato, M.; Ito, K.; Takasugi, H. (Fujisawa Pharmaceutical Co., Ltd.); Use of pyridoindole derivs. in the treatment of ischemic disorders. EP 0451538; JP 1992270280 . |
【2】 Kato, M.; Ito, K.; Takasugi, H. (Fujisawa Pharmaceutical Co., Ltd.); Pyridoindole and processes for preparation thereof. AU 8941406; EP 0361317; JP 1990117675; US 5141945; US 5173493; US 5290785 . |
【3】 Prous, J.; Castaner, J.; Mealy, N.; FK-1052. Drugs Fut 1994, 19, 12, 1075. |
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) | 15498 | 10-methyl-8,9-dihydropyrido[1,2-a]indol-6(7H)-one | C13H13NO | 详情 | 详情 | |
(II) | 15499 | 5-methyl-1-trityl-1H-imidazole-4-carbaldehyde | C24H20N2O | 详情 | 详情 | |
(III) | 15500 | 7-[(Z)-1-hydroxy-2-(methyleneamino)-3-[methyl(trityl)amino]-2-butenyl]-10-methyl-8,9-dihydropyrido[1,2-a]indol-6(7H)-one | C37H33N3O2 | 详情 | 详情 | |
(IV) | 15501 | (10-methyl-6-oxo-6,7,8,9-tetrahydropyrido[1,2-a]indol-7-yl)(5-methyl-1-trityl-1H-imidazol-4-yl)methyl acetate | C39H35N3O3 | 详情 | 详情 | |
(V) | 15502 | 10-methyl-7-[(E)-(5-methyl-1-trityl-1H-imidazol-4-yl)methylidene]-8,9-dihydropyrido[1,2-a]indol-6(7H)-one | C37H31N3O | 详情 | 详情 | |
(VI) | 15503 | 10-methyl-7-[(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]-8,9-dihydropyrido[1,2-a]indol-6(7H)-one | C37H33N3O | 详情 | 详情 |