CL-218872
3-甲基-6-(3-[三氟甲基]苯基)-1,2,4-噻唑并-(4,3-b)吡嗪Chemical Name: 3-Methyl-6-[3-(trifluoromethyl)phenyl]-1,2,4-triazolo[4,3-b]pyridazine
CAS No. 66548-69-4
项目整合开发状态: Biological Testing
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线:The reaction of 3-trifluoromethylbenzaldehyde (I) with morpholine (II) and potassium cyanide by means of p-toluenesulfonic acid in refluxing THF gives alpha-(3-trifluoromethylphenyl)-4-morpholineacetonitrile (III),which is condensed with ethyl acrylate (IV) by means of KOH in THF yielding gamma-cyano-gamma-(3-trifluoromethylphenyl)-4-morpholinebutyric acid ethyl ester (V).The cyclization of (V) with hydrazine in refluxing ethanol affords 4,5-dihydro-6-(3-trifluoromethylphenyl)-3(2H)-pyridazinone (VI),which is dehydrogenated by treatment with Br2 in hot acetic acid to give 6-(3-trifluoromethylphenyl)-3(2H)-pyridazinone (VII).The reaction of (VII) with POCl3 at 100 C affords 3-chloro-6-(3-trifluoromethylphenyl)pyridazine (VIII),which is finally cyclized with acetylhydrazine (IX) in refluxing n-butanol.
📌 参考资料/链接：
参考文献标题:CL-218,872
文献作者:Owen,R.T.; Serradell,M.N.; Blancafort,P.; Castar,J.
参考来源:Drugs Fut 1983,8(3),191
📄 详细内容
合成路线:The reaction of 3-trifluoromethylbenzaldehyde (I) with morpholine (II) and potassium cyanide by means of p-toluenesulfonic acid in refluxing THF gives alpha-(3-trifluoromethylphenyl)-4-morpholineacetonitrile (III),which is condensed with ethyl acrylate (IV) by means of KOH in THF yielding gamma-cyano-gamma-(3-trifluoromethylphenyl)-4-morpholinebutyric acid ethyl ester (V).The cyclization of (V) with hydrazine in refluxing ethanol affords 4,5-dihydro-6-(3-trifluoromethylphenyl)-3(2H)-pyridazinone (VI),which is dehydrogenated by treatment with Br2 in hot acetic acid to give 6-(3-trifluoromethylphenyl)-3(2H)-pyridazinone (VII).The reaction of (VII) with POCl3 at 100 C affords 3-chloro-6-(3-trifluoromethylphenyl)pyridazine (VIII),which is finally cyclized with acetylhydrazine (IX) in refluxing n-butanol.
参考文献标题:Synthesis and anxiolytic activity of 6-(substituted-phenyl)-1,2,4-triazolo[4,3-b]pyridazines
文献作者:Albright,J.D.; Moran,D.B.; Wright,W.B.Jr.; Collins,J.B.; Beer,B.; Lippa,A.S.; Greenblatt,E.N.
参考来源:J Med Chem 1981,24(5),592-600
合成路线:The reaction of 3-trifluoromethylbenzaldehyde (I) with morpholine (II) and potassium cyanide by means of p-toluenesulfonic acid in refluxing THF gives alpha-(3-trifluoromethylphenyl)-4-morpholineacetonitrile (III),which is condensed with ethyl acrylate (IV) by means of KOH in THF yielding gamma-cyano-gamma-(3-trifluoromethylphenyl)-4-morpholinebutyric acid ethyl ester (V).The cyclization of (V) with hydrazine in refluxing ethanol affords 4,5-dihydro-6-(3-trifluoromethylphenyl)-3(2H)-pyridazinone (VI),which is dehydrogenated by treatment with Br2 in hot acetic acid to give 6-(3-trifluoromethylphenyl)-3(2H)-pyridazinone (VII).The reaction of (VII) with POCl3 at 100 C affords 3-chloro-6-(3-trifluoromethylphenyl)pyridazine (VIII),which is finally cyclized with acetylhydrazine (IX) in refluxing n-butanol.
参考文献标题:6-Phenyl-1,2,4-triazolo{8 4,3-b{9 pyridazine hypotensive agents
文献作者:Allen,G.R.Jr.; Hanifin,J.W.Jr.; Moran,D.B.; Albright,J.D.
参考来源:US 4112095
产品链接: CAS No. 66548-69-4››