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【结 构 式】 
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【分子编号】36810 【品名】4-[([1,1'-biphenyl]-2-ylcarbonyl)amino]benzoyl chloride 【CA登记号】 |
【 分 子 式 】C20H14ClNO2 【 分 子 量 】335.7894 【元素组成】C 71.54% H 4.2% Cl 10.56% N 4.17% O 9.53% |
合成路线1
该中间体在本合成路线中的序号：(XIX)Alternatively, treatment of biphenyl-2-carboxylic acid (V) with SOCl2 and DMF in CH2Cl2 provides the acyl chloride (XVI), which is condensed with 4-aminobenzoic acid (XVII) by means of N,N-dimethylaniline in acetone to give the corresponding 4-(2-phenylbenzamido)benzoic acid (XVIII). Treatment of (XVIII) with SOCl2 and DMF in dry THF affords the acyl chloride (XIX), which is finally condensed with the inmidazobenzazepine (XII) by means of pyridine in MeCN and treated with 4N HCl.
| 【1】 Castañer, R.M.; Norman, P.; Rabasseda, X.; Leeson, P.A.; Castañer, J.; Conivaptan Hydrochloride. Drugs Fut 2000, 25, 11, 1121. |
| 【2】 Yamazaki, A.; Tanaka, A.; Tsunoda, T. (Yamanouchi Pharmaceutical Co., Ltd.); Novel preparation method of condensed benzazepine derivs.. JP 1996198879 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 18505 | [1,1'-biphenyl]-2-carboxylic acid | 947-84-2 | C13H10O2 | 详情 | 详情 |
| (XII) | 41817 | 2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine | 318237-73-9 | C12H13N3 | 详情 | 详情 |
| (XVI) | 18506 | [1,1'-biphenyl]-2-carbonyl chloride | C13H9ClO | 详情 | 详情 | |
| (XVII) | 20004 | p-aminobenzoic acid; 4-aminobenzoic acid | 150-13-0 | C7H7NO2 | 详情 | 详情 |
| (XVIII) | 41820 | 4-[([1,1'-biphenyl]-2-ylcarbonyl)amino]benzoic acid | C20H15NO3 | 详情 | 详情 | |
| (XIX) | 36810 | 4-[([1,1'-biphenyl]-2-ylcarbonyl)amino]benzoyl chloride | C20H14ClNO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)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 |
合成路线3
该中间体在本合成路线中的序号：(VII)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 reduction of both lactam groups of (V) with LiAlH4 gave the pyrrolobenzodiazepine (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) | 36811 | methyl (2R)-2-pyrrolidinecarboxylate | C6H11NO2 | 详情 | 详情 | |
| (IV) | 36807 | methyl (2R)-1-(2-nitrobenzoyl)-2-pyrrolidinecarboxylate | C13H14N2O5 | 详情 | 详情 | |
| (V) | 36808 | (11aR)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione | C12H12N2O2 | 详情 | 详情 | |
| (VI) | 36809 | (11aR)-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 |