【结 构 式】 |
【分子编号】14052 【品名】N-[6-Acetyl-3-(2-chlorobenzoyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl]-2-bromopropanamide 【CA登记号】 |
【 分 子 式 】C19H18BrClN2O3S 【 分 子 量 】469.7863 【元素组成】C 48.58% H 3.86% Br 17.01% Cl 7.55% N 5.96% O 10.22% S 6.83% |
合成路线1
该中间体在本合成路线中的序号:(III)1-Acetyl-4-piperidone (I) is condensed with 2-chlorocyanoacetophenone in the presence of sulfur and base to give the thiophene (II). Treatment of (II) with 2-bromopropionyl bromide gives the amide (III), which on reaction with ammonia gives the amine (IV). Cyclization of (IV) with acetic acid/pyridine gives the diazepine (V). Reaction of the amide of (V) with phosphorus pentasulfide or Lawesson's reagent produces the thioamide (VI), which is reacted with acetic hydrazide to give the triazole (VII). Basic hydrolysis of the amide of (VII) produces the amine (VIII), which is resolved to give the S-enantiomer (IX). Reaction of (IX) with cyclopropanecarbonyl chloride gives the amide (X).
【1】 1,4-Diazepine deriv. and its pharmaceutical use. AU 8943761; EP 0367110; EP 0606103; EP 0677524; JP 1990256682; US 5221671; US 5304553; US 5382579; US 5409909; US 5438045; US 5468740; US 5482937 . |
【2】 Clark, R.S.J.; E6123. Drugs Fut 1991, 16, 4, 310. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
12923 | 3-(2-Chlorophenyl)-3-oxopropanenitrile | 40018-25-5 | C9H6ClNO | 详情 | 详情 | |
14061 | Cyclopropanecarbonyl chloride; Cyclopropanecarboxylic acid chloride | 4023-34-1 | C4H5ClO | 详情 | 详情 | |
(I) | 14050 | N-Acetyl-4-piperidone; 1-Acetyltetrahydro-4(1H)-pyridinone | 32161-06-1 | C7H11NO2 | 详情 | 详情 |
(II) | 14051 | 1-[2-Amino-3-(2-chlorobenzoyl)-4,7-dihydrothieno[2,3-c]pyridin-6(5H)-yl]-1-ethanone | C16H15ClN2O2S | 详情 | 详情 | |
(III) | 14052 | N-[6-Acetyl-3-(2-chlorobenzoyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl]-2-bromopropanamide | C19H18BrClN2O3S | 详情 | 详情 | |
(IV) | 14053 | N-[6-Acetyl-3-(2-chlorobenzoyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl]-2-aminopropanamide | C19H20ClN3O3S | 详情 | 详情 | |
(V) | 14054 | 8-Acetyl-5-(2-chlorophenyl)-3-methyl-1,3,6,7,8,9-hexahydro-2H-pyrido[4',3':4,5]thieno[2,3-e][1,4]diazepin-2-one | C19H18ClN3O2S | 详情 | 详情 | |
(VI) | 14055 | 5-(2-Chlorophenyl)-8-ethanethioyl-3-methyl-1,3,6,7,8,9-hexahydro-2H-pyrido[4',3':4,5]thieno[2,3-e][1,4]diazepine-2-thione | C19H18ClN3S3 | 详情 | 详情 | |
(VII) | 14056 | 1-[6-(2-Chlorophenyl)-1,4-dimethyl-7,10-dihydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-9(8H)-yl]-1-ethanethione | C21H20ClN5S2 | 详情 | 详情 | |
(VIII) | 14057 | 6-(2-Chlorophenyl)-1,4-dimethyl-7,8,9,10-tetrahydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine | C19H18ClN5S | 详情 | 详情 | |
(IX) | 14058 | (4S)-6-(2-Chlorophenyl)-1,4-dimethyl-7,8,9,10-tetrahydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine | C19H18ClN5S | 详情 | 详情 |