新产品编号:358041
Chemical Name: N-[3-Chloro-4-(9,10-dihydro-4H-thieno[2,3-c]benzazepin-9-ylcarbonyl)phenyl]-5-fluoro-2-methylbenzamide
CAS No. 205306-03-2
项目整合开发状态: Preclinical
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线: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.
📌 参考资料/链接：
参考文献标题:N-Acylated tricyclic azaheterorings useful as vasopressin antagonists
文献作者:Albright,J.D.; Reich,M.F.; Sum,F.-W.(American Cyanamid Co.)
参考来源:CA 2128955; EP 0640592; JP 1995179430; US 5512563; WO 9747624
📄 详细内容
合成路线: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.
参考文献标题:Tricyclic benzazepine vasopressin antagonists
文献作者:Du,X.; Albright,J.D.(American Cyanamid Co.)
参考来源:US 5736538
合成路线: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.
参考文献标题: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
文献作者:Aranapakam,V.; Albreight,J.D.; Grosu,G.T.; Chan,P.S.; Coupet,J.; Saunders,T.; Ru,X.; Mazandarani,H.
参考来源:Bioorg Med Chem Lett 1999,9(13),1733