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【结 构 式】

【药物名称】VP-339

【化学名称】(S)-N-[4-(10-Oxo-2,3,3a,4,5,10-hexahydro-1H-pyrrolo[1,2-b][2,5]benzodiazepin-5-ylcarbonyl)phenyl]biphenyl-2-carboxamide

【CA登记号】

【 分 子 式 】C32H27N3O3

【 分 子 量 】501.59029

【开发单位】Wakamoto (Originator)

【药理作用】Diuretics, RENAL-UROLOGIC DRUGS, Vasopressin V2 Antagonists

合成路线1

The reaction of 2-nitrobenzoic acid with SOCl2 gives the acyl chloride (II), which is condensed with D-proline (III) by means of TEA in dichloromethane yielding the acyl proline (IV). The reductive cyclization of (IV) with H2 over Pd/C in methanol affords the pyrrolobenzodiazepinedione (V). The selective reduction of the C-11 lactam group of (V) with NaBH4 and TFA in glyme gave the pyrrolobenzodiazepinone (VI), which is finally coupled with 4-[(2-phenylbenzoyl)amino]benzoyl chloride (VII) furnishing the title compound.

1 Naito, A.; Ohtake, Y.; Hasegawa, H.; et al.; Novel vasopressin V2 receptor-selective antagonists, pyrrolo[2,1-a]quinoxaline and pyrrolo[2,1-c][1,4]benzodiazepine derivatives. Bioorg Med Chem 1999, 7, 6, 1247.
2 Matsukawa, H.; Toyofuku, H.; Naito, A.; Ohtake, Y.; Saito, Y.; Naito, K. (Wakamoto Pharmaceutical Co., Ltd.); Biphenyl derivs. and medicinal compsns.. EP 0987266; WO 9843976 .
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) 20951 2-nitrobenzoic acid;o-Nitrobenzoic acid 552-16-9 C7H5NO4 详情 详情
(II) 21099 o-nitrobenzoyl chloride; 2-nitrobenzoyl chloride 610-14-0 C7H4ClNO3 详情 详情
(III) 29552 methyl (2S)-2-pyrrolidinecarboxylate 2133-40-6 C6H11NO2 详情 详情
(IV) 36812 methyl (2S)-1-(2-nitrobenzoyl)-2-pyrrolidinecarboxylate C13H14N2O5 详情 详情
(V) 36813 (11aS)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione C12H12N2O2 详情 详情
(VI) 36814 (11aS)-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine C12H16N2 详情 详情
(VII) 36810 4-[([1,1'-biphenyl]-2-ylcarbonyl)amino]benzoyl chloride C20H14ClNO2 详情 详情
(VIII) 29797 2H-3,1-benzoxazine-2,4(1H)-dione;Isatoic anhydride;4H-3,1-Benzoxazine-2,4(1H)-dione;1,2-Dihydro-4H-3,1-benzoxazine-2,4-dione;1H-benzo[d][1,3]oxazine-2,4-dione 118-48-9 C8H5NO3 详情 详情
Extended Information