SU465791A3 - Method for preparing 5-aryl- (or heteroaryl) -3-hydroxy-1n-1,5-benzodiazepin-2.4 (3n, 5n) -diones - Google Patents

Description

exchange decomposition of a compound of formula I, where Ri is hydrogen, with alkylene oxide in the presence of a strong novel, for example, Triton B. By the proposed method you can obtain, for example, the following products: 3-hydroxy-5-phenyl-7-trI: fluoromethyl-1H-1 , 5-be zodiazepin-2, 4- (3N, 5H) -dione; 7-bromo-3-hydroxy-5-phenyl-1H-1.5 - benzodiaz pin-2,4- (3N, 5H) -dione: 7-chloro-3-hydroxy-5-phenyl-1H-1.5 - benzodiaz psh1-2,4- (3N, 5H) -dione; 3-Oxy-1-methyl-5-phenyl-7-trifluoromethyl-1H -1,5-benzodiazepin-2,4- (3N, 5H) -dione; 7-bromo-3-hydroxy-1-methyl-5-phenyl-1H-1,5-benzodiazepin-2,4- (3N, 5H) -dione; 7-chloro-3-hydroxy-1-methyl-5-fe1Nyl-1H- | 1,5-benzodiazepin-2,4- (3N, 5H) -dione; 7-fluoro-3-oxo; 1-methyl-5-phenyl-1H-1.5 - benzodiazepin-2,4- (3N, 5H) -dione; 3-ca Cu-1-methyl-7-nitro-5-phenyl-1H-1,5-benzodiazeia -2,4- (3N, 5H) -diol; 1-ethyl-7-bromo-3-axi-5-fbNyl-1H-1,5-benzo diazepin-2,4- {3N, 5H) -dione; 1-ethyl-3-hydroxy-5-phenyl-7-trifluoromethyl-III -1,5-benzodiazepin-2,4- (3N, 5H) -dione; 3-hydroxy-1-methyl-5- (o-trifluoromethylphenyl) -7-trifluoromethyl-1H-1, 5-benzodiazepin-2.4 - (3H 5H) -dione; 3-hydroxy-5- (o-trifluoromethylphenyl) -7-chloro-1H-, 5-benzodiazepin-2.4 (3H, 5H) -dione; 3-hydroxy-1-methyl-b- (l-nitrophenyl) -7-trnfluoromethyl-1H-, 5-benzodiazepin-2,4- (3N, 5H) -dione; 5 - ("- chlorophenyl) -3-hydroxy-1-methyl-7-trifluoromethyl-1H-1, 5-benzodiazepine - 2.4 - (3H, 5H) -dione; 3-hydroxy-1-isopropyl-5-phenyl-7-trifluoromethyl-1H-1, 5-benzodiazip-2,4- (3N, 5H) -dione; 3-hydroxy-1-hydro, xethyl-5-phenyl-7-trifluoromethyl-1H-1, 5-benzodiazepin-2,4- (3N, 5H) -dione; 1-allyl-3-hydroxy-5-phenyl-7-trifluoromethyl-1H-1; 5-benzodiazepin-2,4- (3N, 5H) -dione; 5- (o-fluorophenyl) -3-hydroxy-1-methyl-7-trifluoromethyl-Sh-1, 5-benzodiazepin-2,4- (3N, 5H) -dione; 3-hydroxy-1-methyl-5- (o-nitrophenyl) -7-trifluoromethyl-1H-1, 5-benzodiazepin-2.4 - (3N, 5H) -dione; 5- (o-bromophenyl) -7-chloro-3-hydroxy-1-methyl-1H-1, 5-benzodiaze-1CH-2,4- (3H, 5H) -diop; 5- (o-chloro-phenyl) -3-hydroxy-1-methyl-7-trifluoromethyl-1H-1, 5-bvnzodiazepin-2,4- (3N, 5H) -dione; 7-chloro-3-hydroxy-1-methyl-5- (o-trifluoromethylphenyl) -1H-4,5- | benzodiazepin-2,4- (3N, 5H) -dione; 5- (l-fluorophenyl) -3-hydroxy-1-methyl-7-trifluoromethyl-1H-1, 5-benzodiaz (Pi -2.4- (3N, 5H) -dione; 3-hydroxy-1-methyl- 5- (l-nitrophenyl) -7 trifluoromethyl-1 H-1,5-benzod} 1 azepin-2,4- (3N, 5H) -dione; 5- (chlorophenyl) -3-hydroxy-1-methyl-7 -trifluoro5 methyl-1H-, 5-benzodiazepin-2,4- (3N, 5H) -dione; 7-chloro-3-hydroxy-; 1-methyl-5- (a-pyridyl)-1H-1, 5 -benzodiazene (PIN-2,4- (3N, 5H) -dione; 7-bromo-3-hydroxy-1-methyl-5- (a-pyridyl) - Sh10 -1,5-benzodiazepia-2,4- ( ZN, 5H) -dione. Example 1. 7-bromo-3-hydroxy-5-fbNyl-S-1,5-benzodiazepin-2, 4- (3N, 5H) -dione. 10 g (0.027 mol) 7- bromo-3,3-dioxy-5-phenyl-1H-1, 5-benzodiazepin-2,4- (3N, 5H) -dione 5 in 150 ml of glacial acetic acid The solution is heated with 12 g of zinc powder for 30 minutes while the solution is heated to boiling. The hot solution is separated from zinc, which is additionally washed with acetic acid. Then the solution is diluted with 600 ml of ice water, crystallized for 1 hour, the precipitated the crystals are washed with water. After drying, 9.1 g of the crude product is obtained, which is recrystallized from alcohol. Output 9.0 g (94% of theory); m.p. 264--266 ° C. Example 2. 7-bromo-3-hydroxy-1-methyl-5-phenyl-1H-, 5-benzodiazepin-2,4- (3N, 5H) -dione. To 6.9 g (0.02. Mol) of 7-bromo-3-hydroxy-5-phenyl-1H-1, 5-benzodiazepin-2,4- (3N, 5H) -dione (likewise ) in 350 ml of tetrahydrofuran, 500 mg of a 50% sodium hydride dispersion is added. Stir for 30 minutes, add 40 ml of methyl iodide, stir further for 5 hours at room temperature, evaporate and take up the residue in L. tetrachloride. The washed and dried pacTiBOp methylene chloride is evaporated and the residue is recrystallized from methanol. Yield 5.3 g (74% of theory); m.p. 269-27GS. Example 3. 7-chloro-3-oxn-1-methyl-5- (o-trifluoromethylphenyl) -1H-1,5-benzodiazepine - (3N, 5H) -dione, 9.2 g (0.025 mol) 7-chloro -3,3-dioxy-1-methyl-5- (o-trifluoromethylphenyl) -1 H-1,5-benzodiazepine- (3N, 5H) -dione in 100 ml of ethanol, 15 g of granulated tin, 50 ml of diluted (1 : 1) hydrochloric acid is heated at 50 ° C to complete the reaction. Then the reaction mixture is filtered over kieselgur, the residue on the filter is additionally washed with ethyl acetate, the solution is evaporated, the residue is taken up in. Methylene chloride and an alkaline feed is made using ammonia. The methiechloride is separated, washed, dried over magnesium sulfate, the solvent is evaporated in vacuo and the residue is recrystallized from acezonitrile. Obtain 5.2 g (60% of theory) of solubility with m. Pl. 260-262 ° C. The table shows the data of compounds obtained similarly.

5H) -diones of general formula I

ABOUT

wherein RI is hydrogen, a straight or branched alkyl group with 1-4 carbon atoms, which, if necessary, may contain an oj-hydroxy group, an alkyl or cyclopropylmethyl group;

RS is a phenyl radical which, if necessary, can be substituted by a halogen atom, a trifluoromethyl or a nitro group, or a pyridyl radical and

A 3-atom of fluorine, chlorine or bromine, or a trifluoromethyl, or nitro group, characterized in that the compound of the general formula II

Subject invention

1. The creeping method of 5-aryl- (or heteroaryl) -3-o si-1H-: 1.5 - benzodiazepine -2.4 - (3N,

where Ri, Kr and Kz are as defined above, they are reduced, followed by separation of the target product in a known manner.

2. A method according to claim 1, characterized in that zinc-acid acetic acid or tin-salt 40 acid is used as a reducing agent.