SU507224A3 - Method for preparing substituted amino ketones or corresponding amino alcohols - Google Patents

Description

the residue is substituted by an alkyl group of CY-C and / or an alkoxy group of C and / or a hydroxyl group and / or a halogen atom. The proposed method for the preparation of compounds of formula 1 is that the compound of general formula 1 (in which R is OXY-, alkoxy, amino or monoalkylamino. Ac, X, Aei, R have the above values, is acylated in the usual way, after which the compounds are isolated in free form or in salt form, or restore free keto groups or acylate over the remaining free hydroxy or amino groups, the acylation of hydroxy and / or amino groups is carried out in a known manner, for example, by treatment with acids or functional Acid derivatives such as acid halide, acid anhydride, acid amide, ester. The treatment can be carried out both in the presence and in the absence of solvents, at O - 300 ° C. When using free acids, the temperature is usually level up Alcohols, aromatic hydrocarbons, dioxane, tetrahydrofuran, aliphatic ethers dimethyl sulfoxide, aliphatic ketones, N-methyl pyrrolidone, sulfolane can be used as a solvent. It is advisable to add basic substances, such as hydrates of oxides of alkali and alkaline earth metals, their alcohols, carbonates or acetates, tertiary amines, pyridine. When using ketoic esters and free acids, the presence of basic substances is not necessary. Depending on the position in the molecule, the hydroxy or amino groups have different reactivity. Due to this, it is possible to selectively acylate. Aromatic amino groups are most easily acylated. Selectively acylation of these amino groups can be accomplished, for example, by treatment with an equimolar amount of an acid chloride or acid anhydride in an inert solvent medium in the presence or in the absence of an equimolar amount of an acid binding agent, for example, pyridine and triethylamine, PRE | low temperature, for example. Aromatic alino and aromatic hydroxy groups are acylated, for example, with a calculated amount of acid chloride in the presence of aqueous hydrate of 1H metal oxide at O-ZO or an equimolar amount of acid chloride or acid anhydride in a solvent such as diethyl ether, dioxane, dimethylforma, dioxane, and dimethylformamide in an environment of a solvent such as diethyl ether, dioxane, or dimethylformamide in an environment of a solvent such as diethyl ether, dioxane, or dimethylformamide in an environment of a solvent such as diethyl ether, dioxane, dimethylformamide, dimethylformacid, etc. in the presence of an excess of an acid binding agent, for example pyridine, triethylamine, at low temperatures, for example, 0-30 ° C. Under more stringent conditions, it is also possible to produce acylation of such hydroxy groups that do not belong to aromatic ones. For this purpose, for example, an excess of acid chloride or acid anhydride is used in a solvent medium, for example, dioxane and chloroform, in the presence of an excess acid-binding agent, for example pyridine, triethylamine or using pyridine as a solvent, and the reaction is carried out at elevated temperatures, for example 40-14O with. The reduction of keto groups can be carried out, for example, with hydrogen in the presence of a catalyst, such as palladium, platinum oxide, and Nickel Rene, under SO-YUO C under a pressure of 1-50 atm. Suitable chemical reduction agents are hydrides, in particular complex alkali metal hydrides, such as sodium borohydride, lithium hydride, aluminum or alcohols, for example aluminum isopropylate. As solvents, you can use, for example, water) (alcohols or ethers at O-ISO C. The resulting compounds containing optically active carbon atoms, and usually found in the form of racemates, can be split to obtain optically active isomers by known methods, For example, when optically active acid is used. It is also possible to use optically active or diastereomeric substances as starting materials and to obtain corresponding pure optical products as final products. Ski forksch or diastereomeric structures. Example 1.37.3 g of d, 6 p-1- (4-hydroxyphenyl) -1-hydroxypropyl- (2) -amino-3-nitropropioPhenone hydrochloride is hydrogenated in 250 ml of methanol in the presence of 5 g of pgishad catalyst on barium sulfate at room temperature and at normal pressure. After absorbing the calculated amount of hydrogen, the reduction process is interrupted, the liquid is filtered off from the catalyst, and the solvent is distilled off. Residual hydrochloride d, e - (4-hydroxyphenyl) -1-hydroxypropyl- (2) -amino -3-aminopropiophenone (m.p. 173-174 ° C) is recrystallized from methanol. 20 g of d, E - b - M hydrochloride (.4-hydroxyphenyl) -1-hydroxypropyl- (2) -amino-3-aminopropiophenone are dissolved in 70 ml of dimethylformamide and 70 Nvn of acetone and, after the addition of 1.6 ml of pyridine, are treated with 6 , 7 g of dimethylacrylic acid chloride at room temperature.

After 15 minutes, the hydrochloride d, 6-R) - l- (4-oxyphenyl) -l-oxycipropyl- (2) -amino - b, p -dimethylacrylylaminopropiophenone after the addition of 200 ml of gasoline is discharged in the form of an oil, which is treated with 200 ml of water and left to crystallize, and then recrystallized from methanol. Melting point of the obtained compound is 200 ° C.

The starting material is prepared as follows: 90.7 g of 3-nitroacetophenone, 101.5 g of d-hydrochloride, C-4-oxino-ephedrine and 19.5 paraform are heated in 400 ml of isopropanol for 4 hours at reflux temperature. The hydrochloride of -1- (4-hydroxyphenyl) -1-hydroxypropyl-2) -amino3-3-nitropropiophenone (a precipitate is recrystallized from methanonol).

Example 2-N-ji-l-phenyl-1-hydroxypropyl- (2) -aMHHo-3-uHHHaNM "aminopropiophenone.

19.3 g of C p - -1-phenyl-1-hydroxypropyl- (2) -amino-3-an-nshnopropiophenone hydrochloride are dissolved in 120 m of dimethylformamide and, after adding 4.1 ml of pyridine, are treated at room temperature with 9.8 g of cinnamic chloride acid dissolved in 25 ml of acetone at room temperature. After 15 minutes, the C-t 1-phenyl-1-hydroxypropyl- (2) -amino-3-cinnamylaminopropiophenone hydrochloride is treated for crystallization with 300 ml of 3% hydrochloric acid and recrystallized from methanol. Boiling point: 122-127 s.

Example 3. 1-phenyl-1-hydroxypropyl-: (2) -amino-3- (4-methylcinnamylamino) propiophenone.

16.7 g of C f - t 1-phenyl-1-hydroxypropyl- (2) -amino1-3-aminopropiophenone hydrochloride are dissolved in 120 ml of dimethylformamide, and after adding 4 ml of pyridine, 9 g of methyl brownish chloride dissolved in 25 ml of acetone. After 15 minutes, the hydrochloride of P - 1-phenyloxypropyl) - (2) -amino1-3- (4methylcyanamylamino) -propiophenone is made up by adding 300 ml

3% hydrochloric acid before crystallization and recrystallized from ethanol with the addition of a few drops of an isopropanol solution of hydrochloric acid. Melting point 144 ° C.

Example 4. d, (4-Hydroxyphenyl) -1-hydroxypropyl- (2) -amino-3-methylcinnamylamino-propiophenone.

17.5 E (l- (4-hydroxyphenyl) -1-hydroxypropyl- (2) -amino-3-aminopropiophenone hydrochloride is dissolved in 120 ml of dimethylformamide and, after added 4 ml of pyridine, 9 g of methylcinnamic acid chloride dissolved in 25 ml is added acetone at room temperature. After 15 minutes, d, (4-hydroxyphenyl-1-hydroxypropyl) - (2) -amino-3- (4-methylcinnamylamino) -propyfonone hydrochloride is treated with 300 ml of l / 3% hydrochloric acid for in order to cause its crystallization and recrystallized from isopropanol with the addition of several chaples of isopropanol: solution ol hydrochloric acid. Melting point 186-187 C.

Example 5. d, (4-Hydroxyphenyl) -1-hydroxypropyl- (2) -amino-3-cinnnamylaminopropiophenone.

17.5 d, hydrochloride, (4-hydroxyphenyl) -1-hydroxypropyl- (2) -amino-propiophenone is dissolved in 120 ml of dimethylformamide, and after adding 4 ml of pyridine, 8.3 g of cinnamic acid chlorangride dissolved in 25 ml of acetone are treated at room temperature. After 15 minutes the hydrochloride d, E - | - l- (4-hydroxyphenyl) -1-hydroxypropyl- (2) -amino-3-cinnamylaminopropio1) enone is treated with 300 ml of 3% hydrochloric acid in order to cause crystallization, dissolved in ethanol and precipitated with water, and then dried for 3 hours at 70 ° C. Melting point 147-148 ° C. Example 6.d, (4-Hydroxyphenyl) -1-hydroxypropyl- (2) -amino1-3- (4-chlorocinnamylamino) -propiophenone.

17.5 g of 3, (4-hydroxyphenyl) -1-hydroxypropyl- (2) -amino-3-aminopropiophenone hydrochloride are dissolved in 120 ml of dimethylformamide, and after adding 4 ml of pyridine, 10.5 g of 4-chloro-boric acid chloride dissolved in in 25 mp acetone, at room temperature. According to 15 min. N hydrochloride, d, 1- (4-hydroxyphenyl) -1-hydroxypropyl- (2) -amino-3- (4-chlorocinnamidamino) propiophenone is treated with 300 ml of l-3% hydrochloric acid for to cause crystallization, and recrystallized from isopropanol with the addition of a few drops of isopropanol solution of hydrochloric acid. Melting point 160-162 ° C. Example 7 e - | b - 1-Phenyl-hydroxypropyl- (2) -amino-3- (4-chlorocinnamylamino) propiophenone. 16.7 g of E j-l-phenyl-1-hydroxypropyl- (2) -amino-3-aminopropiophenone hydrochloride are dissolved in 120 ml of dimethylformamide and, after adding 4 pyridine, are treated with 4-chlorocinnamic acid chloride, dissolved in 25 ml of acetone at room temperature After 15 minutes, the hydrochloride E - / 5 - 1-Phenyl-1-hydroxypropyl- (2) -amino-3- (4-chlorocyanimylamino) -propiophenone is treated with 300 ml of "3% hydrochloric acid (ACID to cause crystallization, and recrystallized from isopropanol with the addition of a small amount of isopropanol solution of hydrochloric acid. YubS melting point (with decomposition. Example 8. p - 1-Phenyl-1-oxypropyl- (2) -amino-3- (2-chlorocinnamylamino) - propiophenone. 16.7 g of l-phenyl-1-hydroxypropyl- (2) -amino-3-aminopropiophenone hydrochloride are dissolved in 120 ml of dimethylformamide and after p In addition, 4 ml of pyridine is treated with 2-chlorocinnamic acid oranhydride dissolved in 25 ml of acetone at room temperature. After 15 min, hydrochloride E is i-1-phenyl-1-hydroxy- (2) -amino-3- (2-chlorocinnamylamino ) propiophenone is treated with 300 ml of “3% hydrochloric acid in order to cause crystallization and recrystallization from isopropanol with the addition of a small amount of isopropanol hydrochloric acid solution. Melting point 142-14b s (with dilution). Example 9. 3, (4-OKCKphenyl) -1-hydroxypropyl- (2) -aminoJ-3- (2. Chlorocinnamylamino) -propiophenone. 17.5 hydrochloride 5, E - p - 1 (4-ox phenyl) - -propyl- (2) -amino-3-aminopropyfenr solution of yut in 120 ml of dimethyl formamide and after adding 4 ml of pyridine it is treated with 2-chlorocoric acid chloride , dissolved in 25 ml of acetone, at room temperature. After 15 minutes, the hydrochloride d, C - p (4-hydroxyphenyl) -1-hydroxypropyl- (2) -amino - (2-chlorocinnamylamino) propiophenone is treated with 300 ml of 3% hydrochloric acid to cause crystallization, and recrystallized from isopropanol with the addition of a small amount of isopropanol solution of hydrochloric acid. Melting point 1b8-170 ° C. Example 10. T - f -11-Phenyl-1-hydroxypropyl- (2) -amino-3- (3-methoxycinnamylamino) propiophenone. 16.7 g of hydrochloride - | L - l-phenyl -1-hydroxypropyl- (2) -amino7-3-aminopropiophenone is dissolved in 120 ml of dimethyl formamide and after adding 4 ml of pyridine, 9.8 g of 3-methoxycoric chlorohydrin is treated acid, dissolved p 25 ml of acetone, at room temperature. After 15 minutes, the t-f-l-phenyl-1-hydroxypropyl- (2) -amino-3- (3-methoxy-cinnamylamino) -propiophenone hydrochloride is treated with 300 ml of% 3% acid to cause crystallization and recrystallized from isopropanol with the addition of a small amount of isopropanol solution of hydrochloric acid. The solution is stored under diethyl ether, m.p. 172-175 sec. Example 11. 4, f-f-l-hydroxyphenyl) -1-hydroxypropyl- (2) -amino-3- (3methoxycinnamylamino) propiophenone. 17.5 g of d, (4-oxyphenyl) -1-hydroxypropyl- (2) -amino-3-aminopropyphenone hydrochloride are dissolved in 120 ml of dimethylformamide and, after adding 4 ml of pyridine, are treated with .3-methoxycinnamic acid chloride, dissolved in 25 ml of acetone, at room temperature. After 15 minutes, hydrochloride d, B - fi-l - (4-oxyphenyl-1-oxypropyl- (2) -mino-3-methoxycinnamylamino) -propiophenone is treated with 300 ml of v 3% hydrochloric acid to cause crystallization, and recrystallization from isopropanol with the addition of an isopropanol solution of hydrochloric acid. The solution is stored under diethyl ether, m.p. 193-195С. Example 12. d, (4-Oxiphenyl) - -oxipropyl- (2) -amino-3- (ot-methylcinnamylamino) -propiophenone. 17.5 g of hydrochloride b, f - (4-oxyphenyl-1-hydroxypropyl- (2) -aminH-3-aminopropioPhenone is dissolved in 120 ml of dimethylformamide, and after adding 4 ml of pyridine, 9 g of chloroanhydride A-methylcinnamic acid dissolved in 25 ml of acetone at room temperature. After 15 minutes, d, C-Ji-f i- (4-hydroxyphenyl- (2) -amino-3-ii-methylcinnamine aminopropiophenone) hydrochloride is treated with 300 ml of "3% hydrochloric acid for crystallization, and recrystallized from isopropanol with the addition of an isopropanol solution of the acid. melting point 178-180 ° C. Example 13. 1-Phenyl-1-hydroxypropyl- (2) -amino-3- (4-methoxy-aminamylamino) -propiophenone 16.7 g of hydrochloride t, f -fl-phenyl-1-hydroxypropyl - (2) -amino-3-aminoropiophenone was dissolved in 120 ml of diethylformamide and after adding 4 ml of pyridine, 9.3 g of lorane anhydride of 4-methoxycinnamic acid, dissolved in 25 ml of acetone, were heated at room temperature. After 15 min, the hydrochloride was added. p-l-phenyl-hydroxypropyl- (2) -amino-3- (4-methoxy-cinnamylamino) -propiophenone is treated with 300 ml of 3% hydrochloric acid to cause crystallization, and Recrystallized from isopropanol with the addition of a small amount of isopropanol hydrochloric acid solution. Melting point 178-180 ° C. Example 14.3, B-p-11- (4-hydroxyphenyl) -1-hydroxypropyl- (2) -amio 1-3- (4toxicynnamilyio) propiophenone. 17.5 g of hydrochloride L, PU- (4-oxoxyphenyl) -1-hydroxypropyl- (2) -amino-3-aminopropiophenone dissolve in 120 dimethylformamide and then, with the addition of 4 ml of pyridine, 9.8 g of methoxychloric acid anhydride are treated, dissolved in 25 ml of acetoia, at room temperature. After 15 minutes, d, 6-fb-- (4-hydroxyphenyl) -1-hydroxypropyl- (2) -amino-3- (4-methoxyethylamino) amino-propiophenone orhydrochloride hydrochloride 300 ml of 3% hydrochloric acid for to cause crystallization and recrystallize from isopropanol with the addition of a small amount of isopropanol solution of hydrochloric acid. The solution is stored under diethyl ether and incubated for many days. Melting point 183-184 ° C. Example 15 - / b -tl-phenyl-1-oxypropyl -. (2) - yumii-3-fioxycar bonylaminopropiophenone. 16.7 g of 1-p -C-phenyl-1-hydroxypropyl- (2) -amio} -3-aminopropiophenoium hydrochloride are dissolved in 120 ml of dimethylformamide, and after adding 4 ml of pyridine, 7.8 g of phenyl chloroformic acid dissolved in 25 ml of acetone, at kokshatny temperature. After 15 kshn shdrohlorid C {- l-phenyl-l-okcippopil- (2) -aminol-3-fenokcikapbonilaminoppopiofenona treated with 300 ml of "in 3% hydrochloric acid in order to induce and Kris tgishizgschiyu perekristgshlizovyvayut from ethanol. Temperature; melting, 178-180 ° C. Example 16. a, C-f phenyl) -1-hydroxypropyl- (2) -amino1-3-phenoxycarbonylaminopropiophenone. 17.5 g of d, E-p-Cl- (4oxyfeiyl) -1-hydroxypropyl- (2) -amino) -3-aminopropiophenone hydrochloride are dissolved in 120 MP of dkmethylformamide and after adding 4 MP of pyridine, 7.8 g of feiyl ether are treated chloroformic acid, dissolved in 25 ml of acetone, at room temperature. After 15 minutes, the d, t-p (4-hydroxyphenyl) -1-hydroxypropyl- (2) -amino1-3-phenoxycarbonylamiopropiophenone hydrochloride hydrochloride is treated with 300 ml of 3% hydrochloric acid to cause crystallization and recrystallized from ethanol. Melting point 196-197 ° C. Formula of the invention. A method for producing substituted amino ketones or corresponding aminopirts of the general formula -a where Ar is phenyl or naphthyl; X is an oxygen atom, a hydroxyl group and water i. LSC is an aliphatic radical with a straight or branched saturated or non-saturated hydrocarbon chain containing from 1 to 6 carbon atoms, which can be replaced by a halogen atom, a hydroxyl group, a lower alkoxy or acyloxy group g T - acyloxy, acyloxyalkoxy, acyloxy or acyl group, or acyl group or acyl group. ; 4 volumes of hydrogen or lower alkyl; Ry is a hydrogen atom, lower alkyl or acyl; R is the same or different - hydrogen, halogen, hydroxy-, lower eshkoxy-, acyloxy-, amino-, alkylNo; 1: 1, dialkylamino-, acylamino-, nitro, lower gshkil-, lower haloalkyl- or lower alkylthio. moreover, acyl residues can be residues of saturated or unsaturated branched or unbranched in some cases substituted by halogen, OXI, acyloxy, keto, lower alkoxy or phenyl, fatty acids containing from 2 to 10 carbon atoms, benzoic acids, which may be substituted once or several times by halogen, oxy-acyloxy, lower alkyl or lower alkoxy, or lower aliphatic carbonic acid half-esters, or phenyl complex hemispheres, or saturated or unsubstituted, linear silt and Cj-C branched fatty acids substituted with at least one fecal residue, the phenyl residue being replaced by an alkyl group C and / or an alkoxy group C and / or a hydroxyl group and / or a halogen atom or salts thereof, characterized in that the compound of the general formula I in which R -OXY-, alkoxy-, amino-, whether the monoalkylamino group, and Ah, X, Afk, R-R have the above values, are acylated in the usual way

. :12

I obtained compounds either isolate 2. Pop.1 method, distinguished by free form or in the form of salt, ui and with the fact that the target product

either "restore free keto-isolate as a racemate, or c. wigroup or acylated on the freede optically active isomer or

hydroxy or amino groups. 5 stereo isomer.

507224