SU460627A3 - Method for preparing 5-aryl- (or heteroaryl) -3-hydroxy 1n-1,5-benzodiazepin-2,4- (3n, 5n) -dions - Google Patents

Description

(54) METHOD FOR OBTAINING 5-ARYL- (OR HETEROARIL) -3OXI-1H-1, 5-BENZODIAZEPIN-2,4- (3N, 5H) -DIONES

may be introduced via an exchange decomposition reaction of a compound of the general formula I, where RI is hydrogen, with alkylene oxide in the presence of a strong base, for example, Triton B, in a solvent medium.

Under the proposed method can be obtained the following target products:

3-hydroxy-5-phenyl-7-trifluoromethyl-1H-1, 5-benzodiazepin-2, 4- (3N, 5H) -dione;

7-bromo-3-hydroxy-5-phenyl-1H-1.5 - benzodiazepin-2, 4- (3N, 5H) -dione;

7-chloro-3-hydroxy-5-phenyl-1H-1, 5-benzodiazepin 2, 4- (3N, 5H) -dione;

3-hydroxy-1-methyl-5-phenyl-7-trifluoromethyl-1H1, 5-benzodiazepin-2,4- (3N, 5H) -dione;

7-bromo-3-hydroxy-1-methyl-5 - phenyl-1H-1,5-benzodiazepin-2, 4- (3N, 5H) -diode;

7-chloro-3-hydroxy-1-methyl-5-phenyl-1H-1.5 gbenzodiazepin-2, 4- (3Н, 5Н) -dione;

7-fluoro-3-hydroxy-1-methyl-5-phenyl-1H-1, 5-benzodiazepin-2, 4- (3N, 5H) -dione;

3-hydroxy-1-methyl-7-nitro-5-phenyl-1H-1, 5-benzodiazepin-2, 4- (3N, 5H) -dione;

1-ethyl-7-bromo-3-hydroxy-5-phenyl-1H-1, 5-benzodiazecin-2, 4- (3N, 5H) -dione;

1-ETHYL-3-OXI-5-phenyl-7-trifluoromethyl-Sh1, 5-benzodiazepin-2,4- (3N, 5H) -dione;

3-hydroxy-1-methyl-5- (o-trifluoromethylphenyl) -7-trifluoromethyl-1H-1.5-benzodiazepin-2, 4- (3N, 5H) -dione;

3 - hydroxy - 5 - (o - trifluoromethylphenyl) - 7 chloro-1H -1.5 - benzodiazepine - 2.4 - (3N, 5H) dan;

3-hydroxy - 1 - methyl - 5 - (f - nitrophenyl) -7 trifluoromethyl - 1H - 1.5 - benzodiazepine - 2.4 (3H, 5H) -dione;

5- (ft-chlorophenyl) -3-hydroxy-1-methyl-7trifluoromethyl-III-1.5-benzodiazepin-2.4 (3H, 5H) -dione;

3 - hydroxy - 1 - isopropyl - 5 - phenyl - 7 - trifluoromethyl - 1H - 1.5 - benzodiazepine - 2.4 (3N, 5H) -dione;

3 - hydroxy - 1 - hydroxyethyl - 5 - phenyl - 7 - trifluoromethyl - 1H - 1.5 - benzodiazepine - 2.4 (3H, 5H) -dione;

1 - allyl - 3 - hydroxy - 5 - phenyl - 7 - trifluoromethyl - 1H - 1.5 - benzodiazepine - 2.4 (3H, 5H) -dione;

5 - (o - fluorophenyl) - 3 - hydroxy - 1 - methyl 7-trifluoromethyl - 1H - 1.5 - benzodiazepine - 2.4 (3H, 5H) - dione; 7 - chloro - 3 - hydroxy - 1 - methyl - 5 - (o - trifluoromethylphenyl) - 1H - 1.5benzodiazepin-2, 4- (3N, 5H) -dione;

5 - (m - fluorophenyl) - 3 - hydroxy - 1 - methyl 7-trifluoromethyl - III - 1.5 - benzodiazepine - 2.4 (3H, 5H) -dione;

3 - hydroxy - 1 - methyl - 5 - (m - nitrophenyl) 7 - trifluoromethyl - III - 1.5 - benzodiazepine 2, 4- (3N, 5H) -dione;

5 - (p - chlorophenyl) - 3 - hydroxy - 1 - methyl-7 trifluoromethyl - III - 1.5 - benzodiazepine - 2.4 (3H, 5H) -dione;

7 - chloro - 3 - hydroxy - 1 - methyl - 5 - (a - pyridyl) - III - 1.5 - benzodiazepine - 2.4 - (3N, 5H) -dione;

7 - bromo - 3 - hydroxy - 1 - methyl - 5 - (its - pyridyl) - III - 1.5 - benzodiazepine - 2.4 - (3N, 5H) -dione.

The starting compounds of formula II are obtained by the reaction of exchange decomposition of an appropriately substituted 1H-1,5-benzodiazepine 2, 4- (3N, 5H) -dione with tosyl azide in the presence of sodium hydride.

Example 1. 3-Oxy-1-methyl-5-phenyl-7-trifluoromethyl-1H-1, 5-benzodiazepin-2,4- (3N, 5H) dione.

18 g (0.05 mol) of 3-diazo-1-methyl-5-phenyl-7 trifluoromethyl - 1H - 1.5 - benzodiazepine - 2,4dione is heated in a mixture of 100 ml of acetonitrile and 10 ml of water with 1 g of copper powder. At 50-60 ° C, nitrogen evolution begins, which ends after 15 minutes. The reaction mixture is filtered, the filtrate is evaporated, and the residue is crystallized from acetonitrile or dioxane. Yield 14 g (80%), so pl. 245-248 ° C.

Example 2. 7-Chloro-3-hydroxy-1-methyl-5-a-pyridyl-1H-1, 5 - benzodiazepine - 2,4- (ЗН, 5Н) dione.

55 g (0.25 mol) of 3-diazo-7-chloro-1-methyl-5pyridyl-1, 5-benzodiazepine-2,4-dione is added at 50-60 ° C and stirring for 15 minutes to a mixture of 250 ml of acetonitrile and 25 ml of 5% copper sulfate.

The reaction mixture was incubated for 30 minutes, filtered and cooled.

The precipitated crystals are collected. After evaporation from the mother liquor, an additional amount of product is obtained, which is recrystallized from methanol. The output of 5.9 g (79%), so pl. 204-206 ° C.

Example 3. 3-Oxy-1-methyl-5-phenyl-7-trifluoromethyl-1H-1,5-benzodiazepin-2,4- (3N, 5H) dione.

3.4 g of 3-hydroxy-5-phenyl-7-trifluoromethyl-1H-1.5benzodiazepin-2, 4- (3N, 5H) -dione (t. Pl.

260-264 ° C). in 200 ml of tetrahydrofuran is mixed with 500 mg of 50% sodium hydride. After 30 minutes, 20 ml of methyl iodide are added to the reaction mixture and stirred for 5 hours at room temperature. Further

the reaction mixture is evaporated, taken in methylene chloride, washed, dried, evaporated. The residue is crystallized from methanol. The yield of 2.9 g (78%), so pl. 245-248 ° C. Similarly, the following compounds of general formula I are obtained

EI

ABOUT

i-c

(JH ./

N-i.

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Subject invention

1. Method for preparing 5-aryl- (or heteroaryl) -3-hydroxy-1H-1.5-benzodiazepin-2,4- (3H, 5H) -dions of formula I

(JH-OH

where RI denotes a hydrogen atom, a normal or branched alkyl group with 1-4 carbon atoms, which, if necessary, in the CO-position may be substituted by an oxy group, an allyl or cyclopropylmethyl group; R2 - phenyl radical, which, if necessary, can

be substituted by a halogen atom, trifluoromethyl or nitro, or pyridyl radical; Ks is a fluorine, chlorine or bromine atom or a trifluoromethyl or nitro group, characterized in that the compound of the general formula II

.Tf-C:

. ® ©.

15G

/

ABOUT

at,

where R2 and Kz are as defined above, RI is as defined above, with the exception of hydrogen, boiled with water in an inert solvent in the presence of copper powder or a copper salt, followed by separation of the target product in a known manner.