SU503520A3 - Method for preparing benzodiazepine derivatives - Google Patents

Description

(54) METHOD FOR OBTAINING BENZODIAZEPIN DERIVATIVES

This invention relates to a process for the preparation of new benzodonazepine derivatives having valuable pharmacological properties.

Based on the known esterification reaction, the described method allows to obtain new compounds with better faction properties with the closest structural analogues of a similar effect.

To obtain new benzodiazepia derivatives of the general formula

where RI means a linear or branched alkyl radical with 2-3 carbon atoms, which is substituted by an acyloxy group with 1-4 carbon atoms, and R2 is a hydrogen or chlorine atom,

is that composing a general formula

where R J - means an unbranched or branched alkyl radical with 2-3 carbon atoms, substituted "with a group, and Rj has the specified value,

etherification followed by isolation of the target product by known techniques.

The esterification can be carried out by conventional methods, for example, by reacting a compound of the general formula 11 with acyliro & anhydrides or carboxylic acid chlorides. The reaction with succinic anhydride can occur, for example, with or without solvents and usually at a temperature of about 50-200 ° C. It is preferably operated in the presence of tertiary bases, for example pyridine, which also serves as a solvent.

Example. 14 g8-chlorine - 5 - (2 hydroxyethototes) - 1 - phenyl 2,3,4,5 tetragisch) o - 1H

-1.5-benzodiazepish was dissolved in 50 ml of pyridine, and, with ice-cold water, 6.5 g of anhydrous was added. d acetic acid. After twenty hours at komsha temperature, the reaction mixture is poured into water, acidified with dilute hydrochloric acid and extracted with chloroform. Washed and dried chloroform

the solution is evaporated and crystalline 8 - chlorine 5

- (2 - acetoxyethyl) 1 - phenyl 2,3,4,5 tetrahydro - W 1,5 - benzodiazepine - 2-it

recrystallized from isopropanol. Output 16.5 g (92% of theory), so pl. 118-h9 ° C.

Example 2. 16 g8-chloro-1 (2 chlorophenyl) -5- (2 hydroxyethyl) -2,3,4,5 tetrahydride W-1.5-benzodiazepin-2-one and 12 g of succinic anhydride with 50 ml Pyridine is heated for 2 hours in a boiling water bath. After cooling, pour in 500 ml of water. The clear solution is acidified with 5N. hydrochloric acid, and the reaction product crystallizes out. Otsasshayut, washed with water and recrystallized 8 - chlorine 1 phenyl - 5 (2 - succinyloxyethyl) - 2,3,4,5 heterogroup III - 1,5 benzodiazepine - 2 it is from isopropanol. Output 18.5 g (88% of theory), T.PL. 146.O7 ° C.

Similarly, 8 chlorine 1 (2 chlorophenyl) 5 - (2-succinyloxyethyl) 2,3,4,5 tetrahydro III -1.5 If get benzodiazepine -2-one; 81% yield of theory, tll. 149-150 ° C (from ethyl acetate);

eight . chlorine 1 phenyl 5 (3 - succinyloxypropyl) - 2,3,4,5 - tetrahydro - III - 1,5 - bechodiazepin-2 it; 8% yield of theory, so pl. 141-142 ° C (from isopropanol).

Claims (1)

Claims method for producing benzodiazhesh derivatives of general formula I where RJ is an energy-branched or branched alkyl radix with 2-3 carbon atoms, substituted by an acyloxy group with 1-4 carbon atoms, and RI is a hydrogen or chlorine atom, characterized in that the compound of general formula N. CH, where Rl - means unbranched or branched alkyl radical with 2-3 carbon atoms, substituted by a hydroxy group, Yaz has the specified value, sterilization followed by isolation of the target product by known techniques. Priority featured: 10.28.70 when Rj - hydrogen atom chlorine chlorine; RI is an alkyl radical with 2-3 carbon atoms; water is substituted by an acyloxy group with 1-3 carbon atoms. 07/02/71 at Rj alkshfadshsal with 2-3 carbon atoms amesteny suktsinillohgruppa.