合成路线:The alkylation of 2-amino-5-chloro-2'-fluorobenzophenone (II) with 2,2,2-trifluoroethyl trichloromethylsulfonate (A) gives 2-(2,2,2-trifluoroethylamino)-5-chloro-2'-fluorobenzophenone (III),which is bromoacetylated with bromoacetyl chloride (B) in refluxing benzene yielding the bromoacetanilide (IV).This compound is cyclized with NH3 in chloroform affording 7-chloro-1-(2,2,2-trifluoroethyl)-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one (I),which by reaction with P2S5 in refluxing dioxane gives the target compound.
合成路线:The alkylation of p-chloroaniline (V) as before yields N-(2,2,2-trifluoroethyl)aniline (VI),which is then condensed with aziridine (C) affording the substituted aniline (VII).The benzoylation of (VII) with 2-fluorobenzoyl chloride (D) yields the amide (VIII),which is cyclized with P2O5 in refluxing POCl3 giving 7-chloro-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-5-(2-fluorophenyl)-1,4-benzodiazepine (IX).This compound is oxidized with RuO4 in CCl4 to give 7-chloro-1-(2,2,2-trifluoroethyl)-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one (I),which by reaction with P2S5 in refluxing dioxane gives the target compound.
合成路线:1) The alkylation of 2-amino-5-chlorobenzophenone (I) with 2,2,2-trifluoroethyl trichloromethansulfonate (II) in refluxing xylene gives the N-trifluoroethyl derivative (III),which is then cyclized with glycine ethyl ester (A) in refluxing pyridine.2) Compound (III) can also be bromoacetylated with bromoacetyl bromide (B) in refluxing benzene yielding the N-bromoacetyl compound (IV),which is then cyclized with ammonia in CHCl3.3) By alkylation of 7-chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (IX) with NaOMe and 2,2,2-trifluoroethyl iodide in MeOH.
合成路线:The reaction of 4-chloro-N-(2,2,2-trifluoroethyl)aniline (V) with ethyleneimine (C) by means of AlCl3 in benzene affords the N-(2-aminoethyl) compound (VI),which is benzoylated with benzoyl chloride (D) as usual yielding the benzamide (VII).Compound (VII) is cyclized with P2O5 in POCl3 giving 7-chloro-1,2-dihydro-5-phenyl-1-(2,2,2-trifluoroethyl)-3H-1,4-benzodiazepine (VIII),which is finally oxidized with RuO4.
参考文献标题:1-Polyfluoroalkylbenzodiazepines
文献作者:Topliss,J.G.; Steinman,M.; Alekel,R.; Wong,Y.S.; York,E.E.
参考来源:J Med Chem 1973,16(12),1354-60
合成路线:The alkylation of 2-amino-5-chloro-2'-fluorobenzophenone (II) with 2,2,2-trifluoroethyl trichloromethylsulfonate (A) gives 2-(2,2,2-trifluoroethylamino)-5-chloro-2'-fluorobenzophenone (III),which is bromoacetylated with bromoacetyl chloride (B) in refluxing benzene yielding the bromoacetanilide (IV).This compound is cyclized with NH3 in chloroform affording 7-chloro-1-(2,2,2-trifluoroethyl)-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one (I),which by reaction with P2S5 in refluxing dioxane gives the target compound.
合成路线:The alkylation of p-chloroaniline (V) as before yields N-(2,2,2-trifluoroethyl)aniline (VI),which is then condensed with aziridine (C) affording the substituted aniline (VII).The benzoylation of (VII) with 2-fluorobenzoyl chloride (D) yields the amide (VIII),which is cyclized with P2O5 in refluxing POCl3 giving 7-chloro-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-5-(2-fluorophenyl)-1,4-benzodiazepine (IX).This compound is oxidized with RuO4 in CCl4 to give 7-chloro-1-(2,2,2-trifluoroethyl)-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one (I),which by reaction with P2S5 in refluxing dioxane gives the target compound.
参考文献标题:Benzodiazepines and the process for their manufacture
文献作者:Steinman,M.
参考来源:DE 2138773; ES 393953; FR 2102114; GB 1345938
合成路线:The alkylation of 2-amino-5-chloro-2'-fluorobenzophenone (II) with 2,2,2-trifluoroethyl trichloromethylsulfonate (A) gives 2-(2,2,2-trifluoroethylamino)-5-chloro-2'-fluorobenzophenone (III),which is bromoacetylated with bromoacetyl chloride (B) in refluxing benzene yielding the bromoacetanilide (IV).This compound is cyclized with NH3 in chloroform affording 7-chloro-1-(2,2,2-trifluoroethyl)-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one (I),which by reaction with P2S5 in refluxing dioxane gives the target compound.
合成路线:The alkylation of p-chloroaniline (V) as before yields N-(2,2,2-trifluoroethyl)aniline (VI),which is then condensed with aziridine (C) affording the substituted aniline (VII).The benzoylation of (VII) with 2-fluorobenzoyl chloride (D) yields the amide (VIII),which is cyclized with P2O5 in refluxing POCl3 giving 7-chloro-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-5-(2-fluorophenyl)-1,4-benzodiazepine (IX).This compound is oxidized with RuO4 in CCl4 to give 7-chloro-1-(2,2,2-trifluoroethyl)-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one (I),which by reaction with P2S5 in refluxing dioxane gives the target compound.
参考文献标题:1-Polyfluoroalkyl-1,4-benzodiazepin-2-thiones for effecting tranquilization,sedation and treating colvulsions
文献作者:Steinman,M.
参考来源:US 3920818
产品链接: CAS No. 36735-22-5››