SU618035A3 - Method of obtaining a,a-diaryl-b- (tert-amino)-propanol - Google Patents

Description

one

The invention relates to a process for the preparation of new apcanopamines, namely, aif cL diary-y5 - (tert-amino) propanopa,

with pharmacological activity.

Known derivatives of aminopropanol possessing α-adrenergic blocking activity, used in medicine.

For example, there is a known method for the preparation of phenoxypropipamine derivatives of the general formula

R

-If-C-ffif-Xg

TO

OCttxCHCH NHR

About him

the fact that the phenoxypropane derivative of the formula

R

iJ-c-im-XN / r-

g11s

R

-OCHj-T

X —CH — SNg — Na1,

where Y is -CH-CH2 OH O

subjected to interaction with ammonia or amine ij. A process for the preparation of phenoxypropylamine derivatives of the general formula is also described.

/

HH-CO-lf

-c-in II.,

II-OV OCH-CH-SNg-TSH-K

he

where R is hydrogen or alkyl is hydrogen, alkyl, benzyl, phenyl, or 1 and F together mean a two-valence hydrocarbon radical, and one or two of these carbon atoms can be replaced by an acid, sulfur or nitrogen;

Claims (2)

R is hydrogen, alkyl, phenyl; R is alkyl, cycloplc or cyano kip; I is hydrogen, apkip or arapkip, which consists in the fact that the And-aminophenol derivative of the formula T "H-R where I and R have the above value; C is hydrogen or a group of co-and V-CH-W; And X means the group -CH-CHg-Nae OH is brought into interaction with the compound, by the formation of the formula HgV-T R has the above value. However, in the literature there is no information about the method of obtaining AG, L aryl-p - (tert-ampno) -propanopa about the formula C-CH-CH3 I, p. where and {means lower alkyp, where R and together with the nitrogen atom can form a 5- or 6-n heterocyclic ring, benzyl or halo; - hydrogen, alkyl, alkenyl, ok group, alkoxy. At the same time, these compounds treat your pharmacological valuables. The aim of the invention is to expand the range of biologically active compounds. This goal is achieved by the method consisting in the fact that propiophenone of the formula xCH3 O xj, where G means a hexagonal number R have the above values, is added in ether to a solution of Grignard reagent from magnesium and a compound of the formula Y - NaE; where E is halogen, and X is a radical selected from the group of the corresponding alkyl anisole, dialkylchroman, alkylphenetol, bromobenzene or timolmethyl ether, in 1,2-dibromoethane and ether at the boiling point of the reaction mixture. Example. 26 g of c-piperidinopropiophenone is added to a Grignard solution of 4 g of magnesium and 40 g of 4-bromothymol ester in 200 ml of ether (diethyl). After boiling for 4 hours under reflux, the reaction mixture is poured onto ice, acidified with hydrochloric acid, and crystals that have fallen out of the mixture are suctioned out suction, which are x-hot washings with ether and moist into cKiacij of a concentrated solution of ammonia and petroleum ether. After a brief shaking, the crystals dissolve. The petroleum ether extract is separated, dried with potash, and then petroleum ether is evaporated. Get 23.7 g of 1- (4 methoxy-2-methyl-5-isopropylphenyl) -1-phenyl-2-piperidinopropanol- (1) with so pl. 134-135 C. PRI mpe R 2. 22 g of cx - pyrrolidinopropiophenone is added to a Grignard solution of 7.3 g of magnesium, 38.5 g of 4-bromo-5-methyl-2-tert-butyl-isanisole and 28 , 2 g of 1,2-dibromoethane in 300 ml of ether. After refluxing for 4 hours, the reaction mixture was poured onto ice and acidified with hydrochloric acid. The precipitated crystals of oats: sate on suction, washed with ether and introduced into the mixture of a concentrated solution of ammonia and ether. After a brief shaking, the crystals dissolve. The ether extract is separated, dried with potash, and the ether is evaporated. The remaining viscous brown oil is dissolved in a small amount of isopropanol. After some time, 28.2 g of 1- (4-methoxy-2-methyl-5-.-Tert-butylphenyl) -1-pheny-E-2-pyrrolidone-propanol- (1) with a m.p. crystallized out. 112-113 C. A frost of 15g of her-piperidinopropiofenone is added to the solution of Grignard reagent from. 7.3 g of magnesium, 38.5 g of 6-bromo-2-megip-4-tert-butylanisole and 28.2 g of 1,2-dibromoethane in AOO ml ether. After boiling for 4 hours under reflux, the reaction mixture is drunk per ped and acidified with hydrochloric acid. The aqueous solution in the same way as the oily intermediate layer is separated, alkalized all together with a concentrated aqueous solution of ammonia and the liberated base is dissolved in ether. The ether is evaporated, 26.5 g of a viscous, brown oil remain, from which 21.5 g of 1- (2-to-3-methyl-5-tert-butyphenyl 11) -1-phenyl are crystallized out of isopropanol while rubbing 2-piperidinopropanol- (1) with t. Pl. 86-87 C. PRI me R 4. 12 g of 1 (3 dimethoxyphenyl) -2-piperidinopropanol- (1 is added to a solution of Grignard from 7.3 mg, 4O, 6 g of 4-bromo-2,6- diisopropyl anisole and 28.2 g of 1.2 dibromoethane in 300 ml of ether, boil for 4 hours under reflux, the reaction mixture is poured on ice and acidified with hydrochloric acid. The acidic aqueous solution is separated with an oily intermediate layer, all alkalinized together with concentrated aqueous ammonia and the precipitated base is dissolved in ether. After drying the ether extract over potash and evaporation of the ether 24.7 g of a yellow-brown oil remain, from which 14.8 g of 1- (4-methoxy-3-diisopropylphenyl) -l- (4-dimetho-scientifenyl) -2-piperidinopropanol (1) 4-d-1-4-dimethoxiphenyl (1-4-methoxy-3-diisopropylphenyl) is obtained from trituration with isopropane. in crude form 118-119 C — Example 5: 7.5 g L- (pyrrolidinopropiophenoy) are added to the Grignard solution from 3.6 g magnesium, 21.5 g 2-methyl-4 tert-hexyl-6-bromoanisole, 14.1 g of 1,2-dibromoethane and 200 ml of ether. After refluxing for 4 hours, the reaction mixture is poured onto ice and acidified with hydrochloric acid. The acidic aqueous solution, together with the oily intermediate layer, is separated from the ether, collectively alkalinized with an aqueous concentrated solution of ammonia, and the liberated base is dissolved in ether. After evaporation of the ester, 14.8 g of oil remains, from which 8.3 g of 1- (2-megoxy-3-metip-5g-tert-hexyphenip) -1-phenide-2-pyrrolidinopropanol- (1) receive 8.3 g of oil with iopropa-NOL. ) with t. pl. in crude form 96-97 C. Example 3: 15 th; - Piperidinopropiophenone in 2O ml of ether is added to the Grignard solution of 5.4 g of magnesium, 26.5 g of 6-bromo-7.8 -dimethylchroman and 20.7 g of 1,2-dibromoethane in 80 ml of ether. After refluxing for 4 hours, the reaction mixture was poured onto ice, acidified with hydrochloric acid, and the precipitated crystals were sucked off with suction. The crystals are mixed with an aqueous concentrated ammonia solution and the mixture shaken with ether several times. The ether is evaporated. An oil remains which crystallizes over time. After recrystallization from methanol, 5.2 g of pure 1- (7,8-dimethylchromanilized - (b)} - 1-phenyl-2-piperidinopropanol- is obtained. (Mp 125-128 C.) e p 7. 18.0 g of L-piperidinopropiophenone is added to the Green's solution of 7.3 g of magnesium, 36.4 g of 4-bromo--2.3, 5,6-tetramethyl anisole, 28.2 g of 1, 2-dibromoethane and ZOO ml of ether. After boiling for 4 hours under reflux, the reaction mixture is poured on ice and acidified with hydrochloric acid. The acidic aqueous solution together with the intermediate oily layer is separated and basified with an aqueous solution of concentrated BiM ammonia, The base is dissolved in ether. After evaporation of the ether, an oil remains, which by trituration with methanol gives 10.5 g of 1- (4-methoxy II | 3, 5 tetramethylphenyl) -1-phenyl-2-piperidinopropanol- (1) mp 148-150 C. Example 8. 10 g of p-dimethoxy-c-piperidinopropiophenone is added to a Grignard solution of 4.8 g of magnesium, 27.1 g of 4-bromo-2,6- diisopropyl propane, 18.8 g of 1,2-dibromoethane and 200 ml of ether. The mixture is refluxed for 4 hours and the reaction mixture is poured. ice and acidified with hydrochloric acid. The aqueous acidic solution is separated and alkalinized with an aqueous solution of ammonia, the separated base is dissolved in ether. The ether is evaporated, 18.2 g of oil are obtained, from which, by trituration with methanol, 12.9 g of 1- (4-methoxy-3, 5-diisopropylphenyl) -l- (4-methoxypheniphen) -2-piperidinepropanol are obtained with m. . 62-64 0. Example 9. 8rlt-ethoxy-6-piperidinopropiophenone is added to the Grinf solution of 4.8 g of magnesium. 27.1 g of 4-bromo-2,6-diisopropipanisole, 18.8 g of 1,2-d11 bromoethane and 200 mp ether. The booster pump was refluxed for 4 hours and the mixture was poured onto the ped and acidified with hydrochloric acid. The aqueous acidic phase is separated, basified with an aqueous solution of ammonia and shaken repeatedly with ether. Combining the ether extracts is dried over potash, the ether is evaporated and the residue is triturated with isopropanol. Crystalline 1- (4-methoxy-3/5 diisoprophenium p) -1- (4-ethoxyphenyl l) -2-piperidinopropano-1 (1) with m.p. in crude form 81-83 C (8.5 g). Example O. piperidine propiophenone is added to a Grignard solution of 7.3 g of magnesium, 36.4 g of 2-bromo-4-tert-butylanisole; 28.2 g of 1,2-dibromoethane and 300 ml of ether. After boiling for 4 hours with a Hopod / Tnik reverse, the reaction mixture is drunk on a ped and acidified with hydrochloric acid. The precipitated crystals are sucked off on the inside, shaken with ether and mixed with aqueous ammonia until the crystals dissolve. After evaporation of the ether, 33.3 g of the partially crystalline product remain, which is diluted with hot methanol. Upon cooling, 25.8 g of 1- (2-methoxy-5-tert-butylphenyl) -1-phenyl-2-piperidinopropanol- (1) are obtained, with a melting point of mp. 139-140s. Similarly, other diaripaminopropanol derivatives were obtained. The formula of the invention-A method for the preparation of aH a: -daryl- / 2 (tert-amino) -propanopa of the general formula C-W-CH3 I where they mean lower alkyl C, and even p together with the nitrogen atom can form 5- or 6- ring ring; R means hydrogen, alkylC, alkenip C, l hydroxy group, lower apkoxyl Cd, and two adjacent substituents together can form a 5- or 6-membered heterocyclic ring, benzyloxy or halogen, which is also characterized by the fact that propiophenone is general; , ftH Ar-C-CH, where A K means a six-membered ring with I - 1, and I have the values outlined above, is added to the solution of magnesium Grigner reagent and the compound of formula X-Ha2 where H 01 R is halogen, and a radical selected from the group corresponding to alkylanisole, dialkylchroman, alkylphenol, brombe nzola or timolmethyl ether, in 1,2-dibromoethane and ether at boiling of the reaction mixture. Sources of information taken into account in the examination, 1.Patent of the USSR for application No. 1879539 / / 04, cl. C O7 C 93 / O6, issued to a foreign company, Esteraische Schiecktoffwerke AG, Austria, 1972. 2.Patent of England No. 1256735, l. C 2 C, 1971.