SU400101A1 - Method of producing derivatives of p-thienyl - Google Patents

Description

The invention relates to the method of i-ray 11 1 derivatives of p-tnene of the general formula (1)

R.

S

, R,

R

  ..,

C-CH2-N-C-CH-CG

I J, RII

RI KV R4 R

K 4

where the thienyl residue may be a seme1, en one or more lower alkyl radicals;

RI-R is a hydrogen atom or an alkylene radical;

Rs is a hydrogen or hydroxy atom;

Kb and R7 are the same or different, denote a hydrogen atom, halogen, oxy-group, lower alkyl, NIP3H1 halide alkyl or n-alkoxyl group;

RS and Rg are the same or different, denote a hydrogen atom, an oxy group, lower alkyl or lower alkoxry, or their salts with chemically pharmacological properties.

The proposed compounds are new and may find use in medicine as pharmaceuticals.

A known method of producing compounds 1Il: th form. || S (11)

X

: li ll

Nh, I

А.1К

ri 5a:.

where alki is not1) pzr, etg, .1nnap or) azweg) flax nal a saturated al, and a chenic group with the number l in | leropic aunior, (/ g 1 to

alk is a straightforward member, razepzlennl iasysh, enna alkylepopei, solerzh1, but AieHbHieii least, 2 glide atoms in uenii. nrnchem pz carbon atoms: - .cgl; em blessed; OKcnrpynHoii;

HI is aiOM of hydrogen or a lower alkyl group;

R-2 to Kz-od-1 or different, denote a hydrogen atom, halogen, oxngrunum or a., Cox- group,

o6pa6oii (oii comp. HeI 111 and 1 total (III)

2 u

where, Ri, R2 and Hz have the indicated meanings,

dehydrating1: by means of it, which are co6oii pharmacologically active compounds that are nitrile into medications.

However, in the literature there are no reports on the way in which the orders of soybean dinadine of the general formula 1 are obtained, that they have 1, their pharmacological properties are the same.

A method is described for the preparation of obi compounds not described in the literature, of formula I, in that the compounds of the general formula I

HE

i

H

I f3Kb

sn-sn-c-sn b

I I

ill

R,

K2 Ets RS

where the thioyl residue may be substituted with lower alkyl radicals, and the remaining radicals have the indicated meanings, are treated with a dehydrating agent, such as hydrohalic acid, followed by isolation of the target product in a known manner as a base or salt.

The cleavage of water is preferably carried out at elevated temperatures, eg, in the range of temperatures between 20 and 150 ° C.

Glacial acetic acid, benzene, dioxane, etc. are used as solvents.

As a dehydrating agent, inorganic acids can be used, such as sulfuric or hydrohalic acids; organic acids, such as claim 1, maximus and formic acid, zinc chloride, tin chloride, boron trifluoride, acid potassium sulphate, aluminum chloride, phosphorus pentoxide, aluminum oxide, acid chlorides, red phosphorus and iodine in the presence of water.

Those compounds that contain an asymmetric carbon atom and, like. as a rule, they occur in the form of racemates; when water is dehydrated, they can be converted by known methods, by naimer, with the help of an optically active acid, into otic active isomers.

Depending on the conditions of the method, cohesive products are obtained in free form or in

salt form. The resulting free bases can be converted to salts in the usual manner, for example, by acid treatment. Example 1. / - 1-Thienyl- (3) -1-phenylopene (1) -yl- (3) - 1-phenyl-1 -oxynronyl- (2) J-amine. In suspension of 16 g (0.04 mol) of hydrochloride / - 1-thieiyl- (3) -1-phenyl-1-oxynropyl- (3) 1-phenyl-1-hydroxypropyl- (2) -amine IIC1 in 150. Ml glacial acetic acid is passed

gaseous hydrogen chloride, the initial product first goes into solution, and after about 20 mpp, the hydrochloride salt precipitates. The hydrochloride salt and recrystallized from

20% -HoiX) ethanol.

The yield of the product is 10 g, m.p. 228-.

Example 2. / - - 1-Thienyl- (3) -1-phenyl-2-methylpropan- (1) -yl- (3) -1-fennl-1-hydroxypropyl- (2) -amin.

4.1 g (0.01 mol) of hydrochloride / - 1-thieyl (3) -1-phenyl-1-oxp-2-methylpropyl - (3) - 1-phenyl-1-hydroxyroyl-2 (-amine) HC1 is suspended in 30 ml of glacial acetic acid and

treated with gaseous hydrogen chloride until the iolite dissolves. The solvent was distilled off, the residue was basified with ammonia and the base was dissolved in ether. By neutralizing the ethereal solution with a solution of hydrogen chloride in isonronanol, the hydrochloride salt is obtained, which is recrystallized from isopropanol. T. pl. is 215-216 ° C. The output is 3 g.

Example 3. 1 - 1-Thienyl- (13) -1- {4-isoylpropylphenyl) -iropro- (1) -yl- (3) -1-phenyl-1-oxypropyl- (2) -amin.

4.4 g (0.01 mol) of hydrochloride / - 1-thienyl (3) -1-p-isopropyl 1 il-1 - hydroxypropyl - (3) J 1-phenyl-1-oxypropyl- (2) -amin HC1 is suspended 30 ml of glacial acetic acid and hydrogen chloride gas are bubbled in for 30 minutes. The solvent is distilled off and the residue is treated with ammonia. The osiovannas are dissolved in ether and converted to the hydrochloride salt using a solution of hydrogen chloride in isopropanol. After that, the resulting salt is recrystallized from ethanol. T. pl. is 236-23 ° C. The output is 2 years.

Example 4. 1-Thienyl- (3) -1-phenylpropene (1) -yl- (3) -1-phenyl-oxypropyl- (2) -methyl ammonium.

1 - 1 -Phenyl-1-phenyl-1-hydroxyprocyl- (2) methylamine is dissolved in ether and treated with a solution of

hydrogen chloride in isopropanol. The crystallized product is recrystallized from ethiol. T. pl. equal to 202 203С,

Example 5. / - 1-Thienyl- (3) -1-phenyl-1- (3,4-dimethylfeiyl) -propene- (1) -yl- (3) -1-phenyl-1-hydroxypropyl- (2) -amir1.

21.6 g (0.05 mol) of hydrochloride / - 1-thienyl (3) -., P-dimethylfe1 il-1 - hydroxypropyl-1 (3) -1 phenyl-1 -oxypropyl- (2) -amia HC1 suspended B 100 ml of glacial acetic acid and treated with gaseous hydrogen chloride until complete dissolution. Solvent

It is distilled off, the residue is treated with ammonia and the base is dissolved in ether and converted with hydrochloric acid in isopropanol to a hydrochloride salt, and then recrystallized with 50% ethanol. T. pl. is 215-217 C. The yield is 7 g.

Subject invention

The method of obtaining derivatives of Z-thienyl of General formula I

where the thienyl residue may be substituted by lower alkyl radicals;

RI-R4 is a hydrogen atom or a lower alkyl radical;

RS is a hydrogen or oxygrune atom;

Re and R are the same or different, denote a hydrogen atom, halogen, oxygrune, low CH-N-C-CH-X

| where the thienyl residue may be substituted with lower alkyl radicals, and the remaining radicals have the indicated meanings.

your alkyl, alkyl haloalkyl or lower alkoxy group;

Rg and Rg are the same or different, represent a hydrogen atom, a hydroxy group, an alkylene or a lower alkoxy group, or their salts, characterized in that the compounds of the general formula II

Re

eleven

R7 RV CZK R;

They are odoated with a dehydrating agent, for example, hydrohalic acid, followed by extraction of the target product with a known method in a free form or in the form of SOLP.