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【结 构 式】 
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【分子编号】21320 【品名】3-Amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one benzenesulfonate 【CA登记号】 |
【 分 子 式 】C22H21N3O4S 【 分 子 量 】423.49256 【元素组成】C 62.4% H 5% N 9.92% O 15.11% S 7.57% |
合成路线1
该中间体在本合成路线中的序号：(III)2-Aminobenzophenone (I) is acylated with bromoacetyl bromide followed by reaction with ammonia to form the [1,4]benzodiazepine. N1-Methylation produces 1,3-dihydro-1-methyl-5-phenyl-2H-[1,4]benzodiazepin-2-one (II). Treatment with isoamyl nitrate and t-BuOK gives an oxime, which is reduced by catalytic hydrogenation to racemic 3-amino-benzodiazepine (III), which is isolated as the crystalline benzenesulfonic acid salt. Crystallization-induced asymmetric transformation yields 3(S)-(-)-3-amino-1,3-dihydro-1-methyl-5-phenyl-2H-[1,4]benzodiazepin-2-one (IV). Acylation with indole-2-carbonylimidazolide produces MK-329.
| 【1】 Reider, P.J.; Davis, P.; Grabowski, E.J.J.; Hughes, D.L.; Crystallization-induced asymmetric transformation: Stereospecific synthesis of a potent peripheral CCK antagonis. J Org Chem 1987, 52, 955. |
| 【2】 Freidinger, R.M.; Berlin, R.G.; MK-329. Drugs Fut 1989, 14, 9, 862. |
| 【3】 Veber, D.F.; Freidinger, R.M.; Hirshfield, J.; Rittle, K.E.; Springer, J.P.; DiPardo, R.M.; Bock, M.G.; Evans, B.E.; Synthesis and resolution of 3-amino-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-ones. J Org Chem 1987, 52, 3232. |
| 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) | 21101 | (2-aminophenyl)(phenyl)methanone; 2-Aminobenzophenone | 2835-77-0 | C13H11NO | 详情 | 详情 |
| (II) | 21319 | 1-methyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one | C16H14N2O | 详情 | 详情 | |
| (III) | 21320 | 3-Amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one benzenesulfonate | C22H21N3O4S | 详情 | 详情 | |
| (IV) | 21321 | (3S)-3-amino-1-methyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one | C16H15N3O | 详情 | 详情 | |
| (V) | 14005 | 2-Bromoacetyl bromide; Bromoacetyl bromide | 598-21-0 | C2H2Br2O | 详情 | 详情 |
| (VI) | 21323 | 3,5-dichloro-2-hydroxybenzaldehyde; 3,5-Dichlorosalicylaldehyde | 90-60-8 | C7H4Cl2O2 | 详情 | 详情 |
| (VII) | 21324 | 1H-imidazol-1-yl(1H-indol-2-yl)methanone | C12H9N3O | 详情 | 详情 |