合成路线:The reduction of 2-chloroacetylamino-3-(o-chlorobenzoyl)thiophene (I) with NaBH4 in DMF gives 2-chloroacetylamino-3-[(o-chlorophenyl)hydroxymethyl]thiophene (II),which is cyclized by means of sodium isopropoxide in refluxing isopropanol to afford 5-(o-chlorophenyl)thieno[2,3-e]-4,1-oxazepin-2-one (III).The bromination of (III) with Br2 in CHCl3 - pyridine yields 7-bromo-5-(o-chlorophenyl)thieno[2,3-e]-4,1-oxazepin-2-one (IV),which by reaction with P2S5 and NaHCO3 in hot diglyme is converted into 7-bromo-5-(o-chlorophenyl)thieno[2,3-e]-4,1-oxazepin-2-thione (V) (1).The cyclization of (V) with cyclohexanecarboxyl hydrazide (A) in THF gives 7-bromo-5-(o-chlorophenyl)-1-cyclohexylthieno[2,3-e]triazolo[3,4-c]-4,1-oxazepin-2-one (VI).The ring opening of (VI) by treatment with concentrated HBr yields 3-cyclohexyl-4-[3-(o-chlorophenylbromomethyl)-5-bromo-2-thienyl]-5-hydroxymethyl-1,2,4-triazole (VII),which by reaction with SOCl2 is converted into 3-cyclohexyl-4-[3-(o-chlorophenyl-bromomethyl)-5-bromo-2-thienyl]-5-chloromethyl-1,2,4-triazole (VIII).The cyclization of (VIII) with NH3 in methanol a 100 C in a pressure vessel yields 8-bromo-6-(o-chlorophenyl)-1-cyclohexyl-4H-s-triazolo[3,4-c]thieno[2,3-e]-5,6-dihydro-1,4-diazepine (IX),which is finally dehydrogenated by treatment with KMnO4 in refluxing acetone
参考文献标题:Process for the preparation of substd.6-aryl-4H-s-triazolo-[3,4-c]-thieno-[2,3-e]-1,4-diazepines
文献作者:Weber,K.-H.; Langbein,A.; Bauer,A.(Boehringer Ingelheim Pharma GmbH & Co.KG)
参考来源:DE 2533924
合成路线:The reduction of 2-chloroacetylamino-3-(o-chlorobenzoyl)thiophene (I) with NaBH4 in DMF gives 2-chloroacetylamino-3-[(o-chlorophenyl)hydroxymethyl]thiophene (II),which is cyclized by means of sodium isopropoxide in refluxing isopropanol to afford 5-(o-chlorophenyl)thieno[2,3-e]-4,1-oxazepin-2-one (III).The bromination of (III) with Br2 in CHCl3 - pyridine yields 7-bromo-5-(o-chlorophenyl)thieno[2,3-e]-4,1-oxazepin-2-one (IV),which by reaction with P2S5 and NaHCO3 in hot diglyme is converted into 7-bromo-5-(o-chlorophenyl)thieno[2,3-e]-4,1-oxazepin-2-thione (V) (1).The cyclization of (V) with cyclohexanecarboxyl hydrazide (A) in THF gives 7-bromo-5-(o-chlorophenyl)-1-cyclohexylthieno[2,3-e]triazolo[3,4-c]-4,1-oxazepin-2-one (VI).The ring opening of (VI) by treatment with concentrated HBr yields 3-cyclohexyl-4-[3-(o-chlorophenylbromomethyl)-5-bromo-2-thienyl]-5-hydroxymethyl-1,2,4-triazole (VII),which by reaction with SOCl2 is converted into 3-cyclohexyl-4-[3-(o-chlorophenyl-bromomethyl)-5-bromo-2-thienyl]-5-chloromethyl-1,2,4-triazole (VIII).The cyclization of (VIII) with NH3 in methanol a 100 C in a pressure vessel yields 8-bromo-6-(o-chlorophenyl)-1-cyclohexyl-4H-s-triazolo[3,4-c]thieno[2,3-e]-5,6-dihydro-1,4-diazepine (IX),which is finally dehydrogenated by treatment with KMnO4 in refluxing acetone
合成路线:The reaction of 7-bromo-5-(o-chlorophenyl)-3H-[2,3-e]thieno-1,4-diazepine-2-thione (X) with cyclohexanecarboxyl hydrazide (A) in refluxing dioxane gives 7-bromo-5-(o-chlorophenyl)-2-(cyclohexylcarbonylhydrazino)-3H-[2,3-e]thieno-1,4-diazepine (XI),which is cyclized by treatment with SiO2 in refluxing toluene
参考文献标题:Ciclotizolam
文献作者:Blancafort,P.; Serradell,M.N.; Castar,J.; Owen,R.T.
参考来源:Drugs Fut 1981,6(6),342
合成路线:The reduction of 2-chloroacetylamino-3-(o-chlorobenzoyl)thiophene (I) with NaBH4 in DMF gives 2-chloroacetylamino-3-[(o-chlorophenyl)hydroxymethyl]thiophene (II),which is cyclized by means of sodium isopropoxide in refluxing isopropanol to afford 5-(o-chlorophenyl)thieno[2,3-e]-4,1-oxazepin-2-one (III).The bromination of (III) with Br2 in CHCl3 - pyridine yields 7-bromo-5-(o-chlorophenyl)thieno[2,3-e]-4,1-oxazepin-2-one (IV),which by reaction with P2S5 and NaHCO3 in hot diglyme is converted into 7-bromo-5-(o-chlorophenyl)thieno[2,3-e]-4,1-oxazepin-2-thione (V) (1).The cyclization of (V) with cyclohexanecarboxyl hydrazide (A) in THF gives 7-bromo-5-(o-chlorophenyl)-1-cyclohexylthieno[2,3-e]triazolo[3,4-c]-4,1-oxazepin-2-one (VI).The ring opening of (VI) by treatment with concentrated HBr yields 3-cyclohexyl-4-[3-(o-chlorophenylbromomethyl)-5-bromo-2-thienyl]-5-hydroxymethyl-1,2,4-triazole (VII),which by reaction with SOCl2 is converted into 3-cyclohexyl-4-[3-(o-chlorophenyl-bromomethyl)-5-bromo-2-thienyl]-5-chloromethyl-1,2,4-triazole (VIII).The cyclization of (VIII) with NH3 in methanol a 100 C in a pressure vessel yields 8-bromo-6-(o-chlorophenyl)-1-cyclohexyl-4H-s-triazolo[3,4-c]thieno[2,3-e]-5,6-dihydro-1,4-diazepine (IX),which is finally dehydrogenated by treatment with KMnO4 in refluxing acetone
参考文献标题:Imvamune IND receives approval
文献作者:
参考来源:Justus Liebigs Ann Chem.1978,1257
产品链接: CAS No. 58765-21-2››