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【结 构 式】 
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【分子编号】41817 【品名】2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine 【CA登记号】318237-73-9 |
【 分 子 式 】C12H13N3 【 分 子 量 】199.25544 【元素组成】C 72.34% H 6.58% N 21.09% |
合成路线1
该中间体在本合成路线中的序号：(XII)The bromination of 1-(p-toluenesulfonyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one (IX) with Br2 in CHCl3 gives the alpha-bromo ketone (X), which is cyclized with acetamidine hydrochloride (VIII) by means of K2CO3, yielding the expected imidazo-benzazepine (XI). This compound is detosylated with hot H2SO4 to provide 2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine (XII). Acylation of (XII) with 4-nitroben-zoic acid (XIII) by means of pyridine in either hot MeCN or DMF affords the 6-(4-nitro-benzoyl) derivative (XIV), which is reduced with H2 and Raney-Ni in MeOH to the corres-ponding 6-(4-aminobenzoyl) compound (XV). Finally, this compound is condensed with biphenyl-2-carbonyl chloride (XVI) [ obtained by treatment of biphenyl-2-carboxylic acid (V) with oxalyl chloride in CH2Cl2/DMF] by means of pyridine in acetonitrile 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 |
| (VIII) | 15866 | ethanimidamide | C2H6N2 | 详情 | 详情 | |
| (IX) | 14763 | 1-[(4-methylphenyl)sulfonyl]-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one | C17H17NO3S | 详情 | 详情 | |
| (X) | 41815 | 4-bromo-1-[(4-methylphenyl)sulfonyl]-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one | C17H16BrNO3S | 详情 | 详情 | |
| (XI) | 41816 | 2-methyl-6-[(4-methylphenyl)sulfonyl]-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine | C19H19N3O2S | 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 |
| (XIII) | 18119 | 4-nitrobenzoic acid; p-nitrobenzoic acid | 62-23-7 | C7H5NO4 | 详情 | 详情 |
| (XIV) | 41818 | [2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl](4-nitrophenyl)methanone | C19H16N4O3 | 详情 | 详情 | |
| (XV) | 41819 | (4-aminophenyl)[2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl]methanone | C19H18N4O | 详情 | 详情 | |
| (XVI) | 18506 | [1,1'-biphenyl]-2-carbonyl chloride | C13H9ClO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XII)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3
该中间体在本合成路线中的序号：(VIII)
| 【1】 Tsunoda T, Tanaka A, et al.2004.Anew synthetic route to YM087, an argirune asopressin antagonist.Heterocycles, 63: 1113---1122 |
| 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） | 14763 | 1-[(4-methylphenyl)sulfonyl]-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one | C17H17NO3S | 详情 | 详情 | |
| (I) | 11161 | methyl 2-aminobenzoate; Methyl anthranilate | 134-20-3 | C8H9NO2 | 详情 | 详情 |
| (II) | 66212 | methyl 2-(4-methylphenylsulfonamido)benzoate | C15H15NO4S | 详情 | 详情 | |
| (III) | 66213 | methyl 2-(N-(3-cyanopropyl)-4-methylphenylsulfonamido)benzoate | C19H20N2O4S | 详情 | 详情 | |
| (IV) | 66214 | 4-ethynyl-1-tosyl-3,4-dihydro-1H-benzo[b]azepin-5(2H)-one | C19H17N2O3S | 详情 | 详情 | |
| (VI) | 41815 | 4-bromo-1-[(4-methylphenyl)sulfonyl]-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one | C17H16BrNO3S | 详情 | 详情 | |
| (VII) | 41816 | 2-methyl-6-[(4-methylphenyl)sulfonyl]-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine | C19H19N3O2S | 详情 | 详情 | |
| (VIII) | 41817 | 2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine | 318237-73-9 | C12H13N3 | 详情 | 详情 |
| (IX) | 41818 | [2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl](4-nitrophenyl)methanone | C19H16N4O3 | 详情 | 详情 | |
| (X) | 41819 | (4-aminophenyl)[2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl]methanone | C19H18N4O | 详情 | 详情 | |
| (XII) | 18941 | p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride | 122-04-3 | C7H4ClNO3 | 详情 | 详情 |