SU403183A1 - METHOD OF OBTAINING DERIVATIVE TETRAHYDROBENZODIAZEPINONA - Google Patents

Description

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

Based on the known reaction of N-arylation or N-heteroarylation of heterocyclic compounds, and the proposed method allows to obtain new compounds with greater activity than the known compounds of similar effect.

A method for the preparation of tetrahydrobenzodiazepinone derivatives of general formula I is proposed.

halogen, nitro or trifluoromethyl group;

Ks is a hydrogen atom, a halogen, oxn-, trifluoromethyl-, nitro, or cyano group, consisting of the benzodiazeninone derivative of the general formula II

li- (LEi

CH2

/

N - C I II Kz 0

15 where RI and Rs are given as

subjected to arylation or heteroaryl compound of formula III

Rj-x

solvent that does not react with the components of the reaction, like xylene.

Compound II

N-SI

V. J

but

where the radicals Ri and Ra have an immense value, the nüeme of restoring its group with a hydrochloric acid, usually at the same time as the initial closure of the diazenin ring. When using other reducing agents, the closure of a pins may be in the liquidity. Such compounds of formula IV, in which Ra is a nitro hormone, can be selectively reduced.

The compounds (|} of Formula I can form solar-additive sun). Use of hydhisic acids are, for example, hydrohalic acids, sulfuric and methanesulfonic acids.

Example 1. 7-Chloro-5-phenyl-1H-2,3,4,5-tetrahydro-1, 5-beisodiasenin-4-one.

10 g of 7-chloro-1Y-2,3,4,5-tetrahydro-1,5-bepzodiazenin-4-one along with 25 ml of bromobenzene.

50 ml of pyridine, 10 g of copper powder, 1 g of copper (I) chloride and 10 g of potassium acetate are heated in an autoclave to a temperature of 160 ° C for 6 hours. It is then suction filtered through kieselgur, washed with methylene chloride, evaporated in vacuo, 50 ml of concentrated ammonia are added and the mixture is extracted with methylene chloride. The filtrate is dried with magnesium sulfate, evaporated in vacuo, purified with activated carbon, crystallized from a mixture of methylene chloride and isopropyl ether. The yield of 3.5 g (61%), so pl. 166-168 ° C, so pl. hydrochloride 158-161 ° C.

Example 2. 7-bromo-1-hydroxyethyl-5-phenyl-1H2, 3,4,5-tetrahydro-1,5-benzodiazine-4-one.

6 g of 7-bromo-1-hydroxyethyl-1P-2,3,4,5-tetrahydro1, 5-benzodiazepin-4-one, while stirring vigorously, are boiled with 20 ml of bromobenzene, 20 ml of diethylideglycol dimethyl ether, 6 g of acetate Kali,

1 g of copper (I) chloride and 6 g of copper (II) oxide for 3 hours.

After completion of the reaction, coal is added, sucked off in a hot state through kieselguhr, repeatedly washed with methylene chloride,

concentrated in vacuo and recrystallized from methanol. The output of 3.4 g (51%), so pl. 153-154 ° C.

Corresponding to the given examples were obtained the following, and the compounds are listed first in the table.

Subject invention

Claims (5)

1. A method for producing tetrahydrobeisodiazepinop derivatives of general formula I N-CH / 7 g CH, with N- I N4 II Oh s K7 where RI is a hydrogen atom, a saturated or unsaturated, straight or branched chain alkyl radical with 1-6 carbon atoms, an alkyl radical with 2-3 carbon atoms, substituted by an oxy group in the w-position, a cycloalkylmethyl radical with 3 or 6 carbon atoms in cycle; An R2-a-pyridyl or phenyl group, unsubstituted or substituted in the ortho position with a halogen, nitro or trifluoromethyl group; Cs is a hydrogen atom, a halo, oxy, trifluoromethyl, nitro, or cyano group, characterized in that the compound of general formula II N-CH7 SNg N-SS And% where RI and Hz are as defined, subjected to arylation or heteroarylation with a compound of formula III R, -X where R2 is as defined, X is halogen, followed by isolation of the desired product in the free state or as a salt by conventional methods; 2. A method according to claim 1, characterized in that the process is carried out in the presence of copper and an alkali metal acetic acid salt, if necessary with the addition of copper salt (I) or copper oxide. 3. Method according to paragraphs. 1 and 2, characterized in that the process is carried out by heating in an autoclave. 4. Method according to paragraphs. 1-3, characterized in that the process is conducted with the addition of weak an organic base such as pyridine. 5. Method according to paragraphs. 1-4, characterized in that the process is carried out in an inert solvent, for example xylene. Priority of June 11, 1969, for registration number R 1929656.1, on the basis of: RI is a hydrogen atom, saturated or unsaturated, a straight or branched alkyl radical with 1-6 carbon atoms, a cycloalkylmethyl radical with 3 or 6 carbon atoms; Rs-a-pyridyl or phenyl radical, unsubstituted or substituted in the ortho-position by a halogen, nitro or trifluoromethyl group; Rs is a hydrogen atom, halo, hydroxy, trifluoromethyl, nitro, or cyano. The priority of February 13, 1970, application No. P 2006600.6, on the grounds: Ri is an alkyl radical with 2-3 carbon atoms, substituted by an oxy group in the CO-position.