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【结 构 式】

【分子编号】34413

【品名】(5S,7S)-7-methyl-5-(4-nitrophenyl)-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isochromen-5-ol

【CA登记号】

【 分 子 式 】C17H15NO6

【 分 子 量 】329.30924

【元素组成】C 62% H 4.59% N 4.25% O 29.15%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VIIb)

The chiral intermediate (S)-alpha-methyl-1,3-benzodioxole-5-ethanol (IV) was prepared by microbiological reduction of 3,4-methylenedioxyphenyl acetone (I) or, alternatively, by lithiation of 4-bromo-1,2-(methylenedioxy)benzene (II) with sec-butyllithium, followed by addition to (S)-propylene oxide (III). Hydrochloric acid-promoted condensation of (IV) with p-nitrobenzaldehyde (V) in hot toluene gave rise to the dioxolobenzopyran system (VIa-b), which was hydroxylated to (VIIa-b) by air oxidation under alkaline conditions. Hydrazone (IXa-b) was obtained as a mixture of E,Z isomers upon treatment of (VIIa-b) with 2-hydrazinopyridine (VIII) in refluxing EtOH. After mesylation of the alcohol group of (IXa-b) with methanesulfonyl chloride and triethylamine, the resulting mesylate (Xa-b) was cyclized to the dioxolo benzodiazepine (XI) using lithium tert-butoxide in THF. The nitro group of (XI) was finally reduced to the target aniline by transfer hydrogenation with potassium formate in the presence of Pd/C.

1 Anderson, B.A.; Harkness, A.R.; Hansen, M.V.; Harn, N.K.; Lodge, D.; Leander, J.D.; Synthesis and anticonvulsant activity of 3-aryl-5H-2,3-benzodiazepine AMPA antagonists. Bioorg Med Chem Lett 1999, 9, 14, 1953.
2 Anderson, B.A.; Hansen, M.M.; Vicenzi, J.T.; Varie, D.L.; Zmijewski, M.J. Jr.; Harkness, A.R. (Eli Lilly and Company); Physical form of dihydro-2,3-benzodiazepine deriv.. EP 0699676; JP 1996081468; JP 1996081469; JP 1996092255; JP 1998505066; US 5795886 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VIa) 34410 (5R,7S)-7-methyl-5-(4-nitrophenyl)-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isochromene C17H15NO5 详情 详情
(VIb) 34411 (5S,7S)-7-methyl-5-(4-nitrophenyl)-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isochromene C17H15NO5 详情 详情
(VIIa) 34412 (5R,7S)-7-methyl-5-(4-nitrophenyl)-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isochromen-5-ol C17H15NO6 详情 详情
(VIIb) 34413 (5S,7S)-7-methyl-5-(4-nitrophenyl)-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isochromen-5-ol C17H15NO6 详情 详情
(IXa) 34415 [6-[(2S)-2-hydroxypropyl]-1,3-benzodioxol-5-yl](4-nitrophenyl)methanone N-(2-pyridinyl)hydrazone C22H20N4O5 详情 详情
(IXb) 34416 [6-[(2S)-2-hydroxypropyl]-1,3-benzodioxol-5-yl](4-nitrophenyl)methanone N-phenylhydrazone C23H21N3O5 详情 详情
(Xa) 34417 (1S)-1-methyl-2-(6-[(4-nitrophenyl)[(E)-2-(2-pyridinyl)hydrazono]methyl]-1,3-benzodioxol-5-yl)ethyl methanesulfonate C23H22N4O7S 详情 详情
(Xb) 34418 (1S)-1-methyl-2-(6-[(4-nitrophenyl)[(Z)-2-phenylhydrazono]methyl]-1,3-benzodioxol-5-yl)ethyl methanesulfonate C24H23N3O7S 详情 详情
(I) 28466 1-(1,3-benzodioxol-5-yl)acetone 4676-39-5 C10H10O3 详情 详情
(II) 10124 5-Bromo-1,3-benzodioxole; 4-Bromo-1,2-(methylenedioxy)benzene 2635-13-4 C7H5BrO2 详情 详情
(III) 29268 (2S)-2-methyloxirane 16088-62-3 C3H6O 详情 详情
(IV) 29259 (2S)-1-(1,3-benzodioxol-5-yl)-2-propanol C10H12O3 详情 详情
(V) 18184 4-Nitrobenzaldehyde 555-16-8 C7H5NO3 详情 详情
(VIII) 34414 2-hydrazinopyridine C5H7N3 详情 详情
(XI) 34419 (8R)-8-methyl-5-(4-nitrophenyl)-7-(2-pyridinyl)-8,9-dihydro-7H-[1,3]dioxolo[4,5-h][2,3]benzodiazepine C22H18N4O4 详情 详情
Extended Information