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【结 构 式】 
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【分子编号】29260 【品名】(7S)-7-methyl-5-(4-nitrophenyl)-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isochromene 【CA登记号】 |
【 分 子 式 】C17H15NO5 【 分 子 量 】313.30984 【元素组成】C 65.17% H 4.83% N 4.47% O 25.53% |
合成路线1
该中间体在本合成路线中的序号：(VI)The reaction of 5-bromo-1,3-benzodioxole (I) with (S)-(-)-propylene oxide (II) by means of sec-butyllithium in THF gives the (S)-isopropanol derivative (IV) (also obtained by stereoselective reduction of 1-(1,3-benzodioxol-5-yl)-2-propanone (III) with Z. rouxii ATCC 14462 in a phosphate buffer). The cyclization of (IV) with 4-nitrobenzaldehyde (V) by means of HCl in hot toluene yields the benzopyran (VI), which is oxidized with air in aqueous NaOH affording the carbinol (VII). The reaction of (VII) with acetohydrazide (VIII) and HCl in refluxing ethanol gives the acetyl hydrazone (IX), which is mesylated at the secondary OH group with methanesulfonyl chloride and TEA in dichloromethane yielding the mesylate (X). The cyclization of (X) by means of NaOH in methanol provides the nitro benzodiazepine (XI), which is finally reduced with potassium formate and Pd/C in ethanol/water.
| 【1】 Andrasi, F.; Talampanel. Drugs Fut 2001, 26, 8, 754. |
| 【2】 Anderson, B.A.; et al.; Application of a practical biocatalytic reduction to an enantioselective synthesis of the 5H-2, 3-benzodiazepine LY300164. J Am Chem Soc 1995, 117, 49, 12358. |
| 【3】 Andrasi, F.; Berzsenyi, P.; Botka, P.; Farkas, S.; Goldschmidt, K.; Hamori, T.; Korosi, J.; Moravcsik, I.; Tarnawa, I. (Gyogyszerkutato Intezet Kft.); N-Acyl-2,3-benzodiazepine derivs., pharmaceutical compsns. containing them and process for preparing same. EP 0492485; JP 1993070463; US 5519019; US 5521174; US 5536832; US 5604223; US 5639751 . |
| 【4】 Varie, D.L.; Hansen, M.M.; Anderson, B.; Vicenzi, J.T.; Zmijewski, M.J. (Eli Lilly and Company); Stereoselective process for producing dihydro-2,3-benzodiazepine derivs.. EP 0699677; US 5665878 . |
| 【5】 Zmijewski, M.J. Jr.; Varie, D.L.; Hansen, M.M.; Vicenzi, J.T.; Anderson, B.A. (Eli Lilly and Company); Physical form of dihidro-2,3-benzodiazepine deriv.. EP 0699676 . |
| 【6】 Hansen, M.M.; Vicenzi, J.T.; Groleau, E.G.; Varie, D.L.; Zmijewski, M.J.; Anderson, B.A. (Eli Lilly and Company); Crystalline form of dihydro-2,3-benzodiazepine deriv.. EP 0699678 . |
| 【7】 Anderson, B.A.; Varie, D.L.; Vicenzi, J.T.; Zmijewski, M.J.; Hansen, M.M. (Eli Lilly and Company); Stereoselective process for producing dihydro-2,3-benzodiazepine derivs.. US 5919954 . |
| 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) | 10124 | 5-Bromo-1,3-benzodioxole; 4-Bromo-1,2-(methylenedioxy)benzene | 2635-13-4 | C7H5BrO2 | 详情 | 详情 |
| (II) | 29268 | (2S)-2-methyloxirane | 16088-62-3 | C3H6O | 详情 | 详情 |
| (III) | 28466 | 1-(1,3-benzodioxol-5-yl)acetone | 4676-39-5 | C10H10O3 | 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 |
| (VI) | 29260 | (7S)-7-methyl-5-(4-nitrophenyl)-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isochromene | C17H15NO5 | 详情 | 详情 | |
| (VII) | 29261 | (7S)-7-methyl-5-(4-nitrophenyl)-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isochromen-5-ol | C17H15NO6 | 详情 | 详情 | |
| (VIII) | 29262 | acetohydrazide | 1068-57-1 | C2H6N2O | 详情 | 详情 |
| (IX) | 29263 | N'-[(E)-[6-[(2S)-2-hydroxypropyl]-1,3-benzodioxol-5-yl](4-nitrophenyl)methylidene]acetohydrazide | C19H19N3O6 | 详情 | 详情 | |
| (X) | 29264 | N'-[(E)-[6-((2S)-2-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]propyl)-1,3-benzodioxol-5-yl](4-nitrophenyl)methylidene]acetohydrazide | C22H25N3O6S | 详情 | 详情 | |
| (XI) | 29265 | 1-[(8R)-8-methyl-5-(4-nitrophenyl)-8,9-dihydro-7H-[1,3]dioxolo[4,5-h][2,3]benzodiazepin-7-yl]-1-ethanone | C19H17N3O5 | 详情 | 详情 |