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【结 构 式】 
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【分子编号】31904 【品名】4,4-dimethyl-2-[3-(2-nitrobenzyl)-2-thienyl]-4,5-dihydro-1,3-oxazole 【CA登记号】 |
【 分 子 式 】C16H16N2O3S 【 分 子 量 】316.38072 【元素组成】C 60.74% H 5.1% N 8.85% O 15.17% S 10.14% |
合成路线1
该中间体在本合成路线中的序号：(III)The condensation of 4,4-dimethyl-2-(2-thienyl)-4,5-dihydrooxazole (I) with 2-nitrobenzyl bromide (II) by means of first with BuLi and then with tributylstannyl chloride and Pd(PPh)3)4 in ethyl ether gives 4,4-dimethyl-2-[3-(2-nitrobenzyl)-2-thienyl]-4,5-dihydrooxazole (III), which is cyclized by means of HCl in refluxing acetone/water yielding 9,10-dihydro-4H-thieno[2,3-c][1]benzazepin-10-one (IV). The reduction of (IV) by means of LiAlH4 in refluxing THF affords 9,10-dihydro-4H-thieno[2,3-c][1]benzazepine (V), which is finally condensed with 2-chloro-4-(5-fluoro-2-methylbenzamido)benzoyl chloride (VI) by means of triethylamine in dichloromethane.
| 【1】 Aranapakam, V.; Grosu, G.T.; Chan, P.S.; Ru, X.; Saunders, T.; Albreight, J.D.; Coupet, J.; Mazandarani, H.; 4,10-Dihydro-5H-thieno[3,2-c][1]benzazepine derivatives and 9,10-dihydro-4H-thieno[2,3-c][1]benzazepine derivatives as orally active arginine vasopressin receptor antagonists. Bioorg Med Chem Lett 1999, 9, 13, 1733. |
| 【2】 Albright, J.D.; Reich, M.F.; Sum, F.-W. (American Cyanamid Co.); N-Acylated tricyclic azaheterorings useful as vasopressin antagonists. CA 2128955; EP 0640592; JP 1995179430; US 5512563; WO 9747624 . |
| 【3】 Du, X.; Albright, J.D. (American Cyanamid Co.); Tricyclic benzazepine vasopressin antagonists. US 5736538 . |
| 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) | 31903 | 4,4-dimethyl-2-(2-thienyl)-4,5-dihydro-1,3-oxazole | C9H11NOS | 详情 | 详情 | |
| (II) | 21082 | 1-(bromomethyl)-2-nitrobenzene；2-Nitrobenzyl bromide;alpha-Bromo-2-nitrotoluene | 3958-60-9 | C7H6BrNO2 | 详情 | 详情 |
| (III) | 31904 | 4,4-dimethyl-2-[3-(2-nitrobenzyl)-2-thienyl]-4,5-dihydro-1,3-oxazole | C16H16N2O3S | 详情 | 详情 | |
| (IV) | 31905 | 4,9-dihydro-10H-thieno[2,3-c][1]benzazepin-10-one | C12H9NOS | 详情 | 详情 | |
| (V) | 31906 | 9,10-dihydro-4H-thieno[2,3-c][1]benzazepine | C12H11NS | 详情 | 详情 | |
| (VI) | 26681 | 2-chloro-4-[(5-fluoro-2-methylbenzoyl)amino]benzoyl chloride | C15H10Cl2FNO2 | 详情 | 详情 |