Study On The Synthesis Technology Of 7-chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one

7-Chloro-5-phenyl-1 ,3-dihydro-2H-1,4-benzodiazepin-2-one(nordazepam) is an important organic chemical, which is an important intermediate for alprazolam that is one of sedative-hypnotics. In this paper, 2-amino-5-chlorobenzophenone was synthesized by cyclization and catalytic transfer hydrogenation with p-chloronitrobenzene and phenylacetonitrile as starting materials, and the cyclization reaction product was 5-chloro-3-phenyl-2.1 -benzisoxazole;On this basis,2-chloroacetylamino-5-chlorobenzophenone was synthesized on the base of acylation reaction with 2-amino-5-chlorobenzophenone and chloroacetyl chloride as raw materials,2-chloroacetamido-5-chlorobenzophenone was further combined with urotropine in an acidic system to give the final product 7-chloro-5-pheny1-1,3-dihydro-2H-1, 4-benzodiazepin-2-one, the optimum conditions for the synthesis of the intermediates and the target compounds were obtained on a large number of experiments.The optimum process conditions for the preparation of 5-chloro-3-phenyl-2,1-benzisoxazole from p-chloronitrobenzene and phenylacetonitrile were as follows:p-chloronitrobenzene of 3.15g,phenylacetonitrile of 2.65mL, reaction temperature of 30?, reaction time of 4h,sodium hydroxide of 1.93g, solvent ethanol of 25mL. Under this condition, the yield of 5-chloro-3-phenyl-2,1-benzisoxazole was 90.6% and the purity of the product was 99.0%.The optimum process conditions for the preparation of 2-amino-5-chlorobenzophenone from 5-chloro-3-phenyl-2,1 -benzisoxazole and ammonium formate were as follows: 5-chloro-3-phenyl-2,1-benzisoxazole of 3.45g,ammonium chloride of 2.84g, reaction temperature of 50? , reaction time 1.5h,catalyst 5%Pd/C of 0.173g, solvent methanol 50mL. Under this condition, the yield of 2-amino-5-chlorobenzophenone was 92.5% and the purity of the product was 98.7%.The optimum process conditions for the preparation of 2-chloroacetylamino-5-chlorobenzophenone from 2-amino-5-chlorobenzophenone and chloroacetyl chloride were as follows: 2-amino-5-chlorobenzophenone of 3.08g(0.015mol), chloracetyl chloride of 1.36mL, reflux reaction time of 2.5h, solvent cyclohexane of 35mL. Under this condition, the yield of 2-chloroacetamido-5-chlorobenzophenone was 94.5%, the purity of the product was 99.3%.The optimum process conditions for the preparation of 7-Chloro-5-phenyl-1,3-dihydro-2H -1,4-benzoate by microwave irradiation with 2-chloroacetylamino-5-chlorobenzophenone and urotropine were as follows:2-chloroacetylamino-5-chlorobenzophenone of 1.55g, urotropine of 1.40g,microwave temperature of 100?, microwave time of 50min, 36% acetic acid of 2mL,solvent anhydrous ethanol of 25mL. Under this condition, the yield of 7-chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one was 89.6%, the purity of the product was 98.5%.