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【结 构 式】 
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【分子编号】12927 【品名】2-Chloro-N-[3-(2-chlorobenzoyl)-5-(4-isobutylphenethyl)-2-thienyl]propanamide 【CA登记号】 |
【 分 子 式 】C26H27Cl2NO2S 【 分 子 量 】488.47732 【元素组成】C 63.93% H 5.57% Cl 14.52% N 2.87% O 6.55% S 6.56% |
合成路线1
该中间体在本合成路线中的序号：(V)Reaction of 2-(2-chlorobenzoyl)acetonitrile (I) with 4-(4-isobutylphenyl)butyraldehyde (II) and sulfur in DMF/NEt3 gives 2-amino-3-(2-chlorobenzoyl)-5-[2-(4-isobutylphenyl)ethyl]thiophene (III), which is acylated with 2-chloropropionyl chloride (IV) in chloroform to give 2-(2-chloropropionamido)-3-(2-chlorobenzoyl)-5-[2-(4-isobutylphenyl) ethyl]thiophene (V). Compound (V) is treated with sodium iodide in THF followed by liquid ammonia to give 2-(2-aminopropionamido)-3-(2-chlorobenzoyl)-5-[2-(4-isobutylphenyl) ethyl]thiophene (VI), which is cyclized in isopropanol and acetic acid to give 5-(2-chlorophenyl)-5-[2-(4-isobutylphenyl)ethyl]-3-methyl-2,3-dihydro-1H-thieno[2,3-e]-1,4-diazepin-2-one (VII). Compound (VII) gives 5-(2-chlorophenyl)-7-[2-(4-isobutylphenyl)ethyl]-3-methyl-2,3-dihydro-1H-thieno[2,3-e]-1,4-diazepin-2-thione (VIII) upon treatment with Lawesson's reagent. Finally, (VIII) is cyclized with hydrazine hydrate and ethyl orthoformiate.
| 【1】 Tahara, T.; Moriwaki, M.; Abe, M.; Yuasa, S. (Welfide Corporation); PAF-antagonistic thienotriazolodiazepine compounds and pharmaceutical uses thereof. EP 0268242; JP 1989156982; US 4820703 . |
| 【2】 Castaner, J.; Prous, J.; Mealy, N.; Y-24180. Drugs Fut 1993, 18, 11, 1016. |
| 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) | 12923 | 3-(2-Chlorophenyl)-3-oxopropanenitrile | 40018-25-5 | C9H6ClNO | 详情 | 详情 |
| (II) | 12924 | 4-(4-Isobutylphenyl)butanal | C14H20O | 详情 | 详情 | |
| (III) | 12925 | [2-Amino-5-(4-isobutylphenethyl)-3-thienyl](2-chlorophenyl)methanone | C23H24ClNOS | 详情 | 详情 | |
| (IV) | 12926 | 2-Chloropropanoyl chloride; 2-Chloropropionyl chloride | 7623-09-8 | C3H4Cl2O | 详情 | 详情 |
| (V) | 12927 | 2-Chloro-N-[3-(2-chlorobenzoyl)-5-(4-isobutylphenethyl)-2-thienyl]propanamide | C26H27Cl2NO2S | 详情 | 详情 | |
| (VI) | 12928 | 2-Amino-N-[3-(2-chlorobenzoyl)-5-(4-isobutylphenethyl)-2-thienyl]propanamide | C26H29ClN2O2S | 详情 | 详情 | |
| (VII) | 12929 | 5-(2-Chlorophenyl)-7-(4-isobutylphenethyl)-3-methyl-1,3-dihydro-2H-thieno[2,3-e][1,4]diazepin-2-one | C26H27ClN2OS | 详情 | 详情 | |
| (VIII) | 12930 | 5-(2-Chlorophenyl)-7-(4-isobutylphenethyl)-3-methyl-1,3-dihydro-2H-thieno[2,3-e][1,4]diazepine-2-thione | C26H27ClN2S2 | 详情 | 详情 |