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【结 构 式】 
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【分子编号】41578 【品名】N-(4-[[2-([1,1'-biphenyl]-2-ylcarbonyl)-4,5-dihydropyrazolo[3,4-d]thieno[3,2-b]azepin-6(2H)-yl]carbonyl]-3-chlorophenyl)[1,1'-biphenyl]-2-carboxamide 【CA登记号】 |
【 分 子 式 】C42H29ClN4O3S 【 分 子 量 】705.23612 【元素组成】C 71.53% H 4.14% Cl 5.03% N 7.94% O 6.81% S 4.55% |
合成路线1
该中间体在本合成路线中的序号：(XIII)Tetrahydrobenzothiophene-4-one (I) was treated with hydroxylamine to afford oxime (IIa-b) as a mixture of syn and anti isomers, which were condensed with tosyl chloride yielding the oxime O-tosylate (IIIa-b). Beckmann rearrangement of (IIIa-b) in the presence of KOAc gave rise to lactam (IV), and subsequent reduction with borane provided thienoazepine (V). Condensation of (V) with 2-chloro-4-nitrobenzoyl chloride (VI) gave amide (VII). A 7-oxo group was introduced by oxidation of (VII) with KMnO4 in acetone-water. The resulting ketone (VIII) was treated with Bredereck’s reagent to afford the dimethylaminomethylene ketone (IX). Cyclization of (IX) with hydrazine produced the tricyclic compound (X). The nitro group of (X) was then reduced to amine (XI) using stannous chloride. Coupling of (XI) with 2-biphenylcarbonyl chloride (XII) furnished the diacylated derivative (XIII). Finally, selective monodeacylation of(XIII) with NaOH yielded the title compound.
| 【1】 Mazandarani, H.; Coupet, J.; Dusza, J.P:; Chan, P.S.; Ru, X.; Delos Santos, E.G.; Albright, J.D.; The synthesis and vasopressin (AVP) antagonist activity of a novel series of N-aroyl-2,4,5,6-tetrahydropyrazolo[3,4-d]thieno[3,2-b]azepines. Bioorg Med Chem Lett 2000, 10, 8, 695. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IIa) | 41567 | (Z)-6,7-dihydro-1-benzothiophen-4(5H)-one oxime | C8H9NOS | 详情 | 详情 | |
| (IIb) | 41568 | (E)-6,7-dihydro-1-benzothiophen-4(5H)-one oxime | C8H9NOS | 详情 | 详情 | |
| (IIIa) | 41569 | (Z)-4-([[(4-methylphenyl)sulfonyl]oxy]imino)-6,7-dihydro-1-benzothiophene | C15H15NO3S2 | 详情 | 详情 | |
| (IIIb) | 41570 | (E)-4-([[(4-methylphenyl)sulfonyl]oxy]imino)-4,5,6,7-tetrahydro-1-benzothiophene | C15H15NO3S2 | 详情 | 详情 | |
| (I) | 11045 | 6,7-Dihydro-1-benzothiophen-4(5H)-one; 4-Keto-4,5,6,7-tetrahydrothianaphthene; Tetrahydrobenzo(b)thiophene-4-one | 13414-95-4 | C8H8OS | 详情 | 详情 |
| (IV) | 41571 | 4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-one | C8H9NOS | 详情 | 详情 | |
| (V) | 41572 | 5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepine | 180340-57-2 | C8H11NS | 详情 | 详情 |
| (VI) | 26674 | 2-chloro-4-nitrobenzoyl chloride | 7073-36-1 | C7H3Cl2NO3 | 详情 | 详情 |
| (VII) | 41573 | (2-chloro-4-nitrophenyl)(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)methanone | C15H13ClN2O3S | 详情 | 详情 | |
| (VIII) | 41574 | 4-(2-chloro-4-nitrobenzoyl)-4,5,6,7-tetrahydro-8H-thieno[3,2-b]azepin-8-one | C15H11ClN2O4S | 详情 | 详情 | |
| (IX) | 41575 | 4-(2-chloro-4-nitrobenzoyl)-7-[(E)-(dimethylamino)methylidene]-4,5,6,7-tetrahydro-8H-thieno[3,2-b]azepin-8-one | C18H16ClN3O4S | 详情 | 详情 | |
| (X) | 41576 | (2-chloro-4-nitrophenyl)[4,5-dihydropyrazolo[3,4-d]thieno[3,2-b]azepin-6(2H)-yl]methanone | C16H11ClN4O3S | 详情 | 详情 | |
| (XI) | 41577 | (4-amino-2-chlorophenyl)[4,5-dihydropyrazolo[3,4-d]thieno[3,2-b]azepin-6(2H)-yl]methanone | C16H13ClN4OS | 详情 | 详情 | |
| (XII) | 18506 | [1,1'-biphenyl]-2-carbonyl chloride | C13H9ClO | 详情 | 详情 | |
| (XIII) | 41578 | N-(4-[[2-([1,1'-biphenyl]-2-ylcarbonyl)-4,5-dihydropyrazolo[3,4-d]thieno[3,2-b]azepin-6(2H)-yl]carbonyl]-3-chlorophenyl)[1,1'-biphenyl]-2-carboxamide | C42H29ClN4O3S | 详情 | 详情 |