合成路线:The regioselective reduction of 8-methyl-5-(4-nitrophenyl)-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepine (I) with borane-THF complex catalyzed by (R)-2-amino-3-methyl-1,1-diphenyl-1-butanol (II) in dichloromethane gives the 8(R)-methyl derivative (III),which is acetylated with acetic anhydride yielding the 7-acetyl-8(R)-methyl derivative (IV).Finally,the nitro group of (IV) is reduced with hydrazine and Ni-Raney in methanol.
参考文献标题:Optically active 1-(4-nitrophenyl)-4-methyl-7,8-methylenedioxy-3,4-dihydro-5H-2,3-benzodiazepine and process for preparing same
文献作者:Ling,I.; H醡ori,T.; Botka,P.; S髄yom,S.; Simay,A.; Moravcsik,I.(Gyogyszerkutato Intezet Kft.)
参考来源:WO 9501357
合成路线:The reaction of 5-bromo-1,3-benzodioxole (I) with (S)-(-)-propylene oxide (II) by means of sec-butyllithium in THF gives the (S)-isopropanol derivative (IV) (also obtained by stereoselective reduction of 1-(1,3-benzodioxol-5-yl)-2-propanone (III) with Z.rouxii ATCC 14462 in a phosphate buffer).The cyclization of (IV) with 4-nitrobenzaldehyde (V) by means of HCl in hot toluene yields the benzopyran (VI),which is oxidized with air in aqueous NaOH affording the carbinol (VII).The reaction of (VII) with acetohydrazide (VIII) and HCl in refluxing ethanol gives the acetyl hydrazone (IX),which is mesylated at the secondary OH group with methanesulfonyl chloride and TEA in dichloromethane yielding the mesylate (X).The cyclization of (X) by means of NaOH in methanol provides the nitro benzodiazepine (XI),which is finally reduced with potassium formate and Pd/C in ethanol/water.
参考文献标题:Stereoselective process for producing dihydro-2,3-benzodiazepine derivs.
文献作者:Varie,D.L.; Hansen,M.M.; Anderson,B.; Vicenzi,J.T.; Zmijewski,M.J.(Eli Lilly and Company)
参考来源:EP 0699677; US 5665878
合成路线:The reaction of 5-bromo-1,3-benzodioxole (I) with (S)-(-)-propylene oxide (II) by means of sec-butyllithium in THF gives the (S)-isopropanol derivative (IV) (also obtained by stereoselective reduction of 1-(1,3-benzodioxol-5-yl)-2-propanone (III) with Z.rouxii ATCC 14462 in a phosphate buffer).The cyclization of (IV) with 4-nitrobenzaldehyde (V) by means of HCl in hot toluene yields the benzopyran (VI),which is oxidized with air in aqueous NaOH affording the carbinol (VII).The reaction of (VII) with acetohydrazide (VIII) and HCl in refluxing ethanol gives the acetyl hydrazone (IX),which is mesylated at the secondary OH group with methanesulfonyl chloride and TEA in dichloromethane yielding the mesylate (X).The cyclization of (X) by means of NaOH in methanol provides the nitro benzodiazepine (XI),which is finally reduced with potassium formate and Pd/C in ethanol/water.
参考文献标题:Physical form of dihidro-2,3-benzodiazepine deriv.
文献作者:Zmijewski,M.J.Jr.; Varie,D.L.; Hansen,M.M.; Vicenzi,J.T.; Anderson,B.A.(Eli Lilly and Company)
参考来源:EP 0699676
合成路线:The reaction of 5-bromo-1,3-benzodioxole (I) with (S)-(-)-propylene oxide (II) by means of sec-butyllithium in THF gives the (S)-isopropanol derivative (IV) (also obtained by stereoselective reduction of 1-(1,3-benzodioxol-5-yl)-2-propanone (III) with Z.rouxii ATCC 14462 in a phosphate buffer).The cyclization of (IV) with 4-nitrobenzaldehyde (V) by means of HCl in hot toluene yields the benzopyran (VI),which is oxidized with air in aqueous NaOH affording the carbinol (VII).The reaction of (VII) with acetohydrazide (VIII) and HCl in refluxing ethanol gives the acetyl hydrazone (IX),which is mesylated at the secondary OH group with methanesulfonyl chloride and TEA in dichloromethane yielding the mesylate (X).The cyclization of (X) by means of NaOH in methanol provides the nitro benzodiazepine (XI),which is finally reduced with potassium formate and Pd/C in ethanol/water.
参考文献标题:Crystalline form of dihydro-2,3-benzodiazepine deriv.
文献作者:Hansen,M.M.; Vicenzi,J.T.; Groleau,E.G.; Varie,D.L.; Zmijewski,M.J.; Anderson,B.A.(Eli Lilly and Company)
参考来源:EP 0699678
合成路线:The regioselective reduction of 8-methyl-5-(4-nitrophenyl)-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepine (I) with borane-THF complex catalyzed by (R)-2-amino-3-methyl-1,1-diphenyl-1-butanol (II) in dichloromethane gives the 8(R)-methyl derivative (III),which is acetylated with acetic anhydride yielding the 7-acetyl-8(R)-methyl derivative (IV).Finally,the nitro group of (IV) is reduced with hydrazine and Ni-Raney in methanol.
参考文献标题:N-Acyl-2,3-benzodiazepine derivs.,pharmaceutical compsns.containing them and process for preparing same
文献作者:Berzsenyi,P.; Goldschmidt,K.; Moravcsik,I.; K髍i,J.; Andr醩i,F.; Farkas,S.; H醡ori,T.; Tarnawa,I.; Botka,P.(Gyogyszerkutato Intezet Kft.)
参考来源:US 5459137
合成路线:The reaction of 5-bromo-1,3-benzodioxole (I) with (S)-(-)-propylene oxide (II) by means of sec-butyllithium in THF gives the (S)-isopropanol derivative (IV) (also obtained by stereoselective reduction of 1-(1,3-benzodioxol-5-yl)-2-propanone (III) with Z.rouxii ATCC 14462 in a phosphate buffer).The cyclization of (IV) with 4-nitrobenzaldehyde (V) by means of HCl in hot toluene yields the benzopyran (VI),which is oxidized with air in aqueous NaOH affording the carbinol (VII).The reaction of (VII) with acetohydrazide (VIII) and HCl in refluxing ethanol gives the acetyl hydrazone (IX),which is mesylated at the secondary OH group with methanesulfonyl chloride and TEA in dichloromethane yielding the mesylate (X).The cyclization of (X) by means of NaOH in methanol provides the nitro benzodiazepine (XI),which is finally reduced with potassium formate and Pd/C in ethanol/water.
参考文献标题:Stereoselective process for producing dihydro-2,3-benzodiazepine derivs.
文献作者:Anderson,B.A.; Varie,D.L.; Vicenzi,J.T.; Zmijewski,M.J.; Hansen,M.M.(Eli Lilly and Company)
参考来源:US 5919954
产品链接: CAS No. 161832-65-1››