5H-1,4-benzodiazepin-5-ones

A) Preparation of 4-Acetyl-7-Chloro-1,2,3,4-Tetrahydro-1 -Methyl-5H-1,4-Benzodiazepin-5-one A mixture of 68.5 g (0.37 mol) of 5-chloro-N-methylanthranilic acid, 51 g (0.51 mol) of calcium carbonate, 76 g (0.37 mol) of bromoethylamine hydrobromide and 2.5 liters of water was stirred and heated under reflux for 3 hours. A solution of 23.4 g (0.26 mol) of anhydrous oxalic acid in 250 ml of water was slowly added to the refluxing mixture. The precipitated calcium oxalate was filtered off, and the filtrate adjusted to pH 7 with concentrated ammonium hydroxide. The filtrate was then concentrated to dryness in vacuo and the residue heated on the steam bath with 400 ml of 6 N ethanolic hydrogen chloride until the residue was crystalline. Filtration gave 122 g of N-(aminoethyl)-5-chloro-N-methvlanthranilic acid hydrochloride as a solid. 

C) Preparation of 7-Chloro-2 -Dihydro-1-Methyl-5-Phenyl-1H-1,4-Benzodiazepine A mixture of 4.7 g (22.6 mol) of 7-chloro-1,2,3,4-tetrahvdro-1-methyl-5H-1,4-benzodiazepin-5-one and 100 ml of phosphorus oxychloride was heated in an oil bath at 100°C for 15 minutes. The solution was concentrated to dryness in vacuo. The residue was partitioned... 

B Preparation of 7-Ch/oro-1,2,3,4-Tetrahydro-1-Methyl-5H-1,4-Benzodiazepin-5-one A mixture of 25.25 g (0.1 mol) of 4-acetyl-7-chloro-1,2,3,4-tetrahydro-1-methyl-5H-1,4-benzo-diazepin-5-one, 33.3 ml (0.1 mol) of 3N sodium hydroxide and 350 ml of ethanol was heated under reflux for 15 minutes and then concentrated to dryness in vacuo. The residue was treated with 500 ml of water, collected and washed with ethanol to give 20.2 g of 7-chloro-1,2,3,4-tetrahydro-1-methyl-5H-1,4-benzodiazepin-5-one. 

A mixture of 100 g of this solid and 1 liter of acetic anhydride was stirred and heated under reflux for 1.5 hours and then allowed to stand for 18 hours at room temperature. The excess acetic anhydride was removed in vacuo, and the residue was treated with one liter of water and ice and sufficient sodium bicarbonate to make neutral. The solid was collected, sucked dry on the filter, and triturated with hot ethanol. The ethanol solution on cooling gave 30.8 g of 4-acetyl-7-chloro-l,2,3,4-tetrahydro-l-methyl-5H-l,4-benzodiazepin-5-one. 

A suspension of 7-chloro-5-(di-4-morpholinyl)phosphinyloxy-2-methylammo-3H-1,4-benzodiazepine in mesitylene refluxed 2 hrs. at 163-166° 7-chloro-3,4-di-hydro-4-(dimorpholinylphosphinyl)-2-methylamino-5H-l,4-benzodiazepin-5-one.Y 80%. R. Y. Ning et al., J. Org. Chem. 41, 2720 (1976). 

Cyclic secondary amines with pyrrolo[2,l-c][l, 4]-benzodiazepine rings were oxidised with TPAP/NMO/PMS/CH3CN to the corresponding imines. Thns (llaS)-1,2,3,10,ll,lla-hexahydro-5H-pyrrolo[2,l-c][l, 4]-benzodiazepine-5-one gave (llaS)-l,2,3,lla-tetrahydro-5H-pyrrolo[2,l-c][l, 4]benzo-diazepine-5-one [23]. 

The 1,3-dipolar cycloaddition of azidoalkylphosphonates to enamines afforded A2-1,2,3-triazoles which are further converted to the 1,2,3-triazoles [95H(40)543] fused triazoles are similarly obtained when a cyclic enamine was employed. Fused 1,2,3-triazole (88), a xanthine oxidase inhibitor, was prepared by the reaction of an alkyl azide with cyanoacetamide with further elaboration of intermediate (87) by treatment with HMDS in xylene [95FES257]. The fused 4H-l,2,3-triazolo[l,5- ][l,4]benzodiazepin-6(5H)-one (90) was obtained from propargylamide (89) via an intermediate azide [95S647]. 

In another report, 1,5-benzodiazepines have been obtained from reaction of alk-3-yn-l-ones with 1,2-phenylenediamines in ethanol under microwave heating without the need for any catalyst (14GC1120). A palladium-catalyzed domino reaction between 1,2-phenylenediamines and 10,11-dihydro-5H-dibenzo[fc,e][l,4]diazepines starting from 2-bromobenzyl bromides has also been developed (14EJ04773). 

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