SU578304A1 - Method of preparing ureidophenoxyalkanolamine derivatives - Google Patents

Description

(54) METHOD FOR OBTAINING DERIVATIVES OF UREIDOPHENOXYALKANOLAMINE

The invention relates to methods for the preparation of ureidophenoxy alkanol amine derivatives not described in the literature, which have biological activities that can be used in pharmacology and medicine.

A known method for producing phenoxyalkanolamine derivatives of the general formula

Z has the indicated meanings; X is an epoxy group with an amine of the general formula NH2-Kz, where R3 has the indicated meanings; or a compound of the general formula Z-SI (OH) CH2-NH2, | Where Z has the indicated meanings, is alkylated by reacting with acetone while being reduced by hydrogen; or hydrolyze the compound of the general formula

ten

Z-CH (OH) -CH2-NH-Cs

where Z is an alkoxy radical, for example alkyl - O- (CH2) p-O-or alkyl -O- (CH2) "- 0- (CH2) t-0-;

pit - 1-3; i

Cs is a linear or branched alkyl containing 1-5 carbon atoms by reacting a compound of the general formula Z1-X

Z-HCCH

from II o

obtaining phenoxyalkanolamine derivatives.

/

K, -}} H-SO-} H

where Ri is an unbranched alkyl with I-6 carbon atoms, branched alkyl with 3-8 atoms) of 1-carbon, for example isopropyl, isobutyl, greg-butyl, isoamyl, 7reg-amyl or crotyl, or dicloalkyl with 3-7 carbon atoms, for example cyclropyl cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl;

Cs - hydrogen, unbranched alkyl with il - 6 carbon atoms, branched alkyl with 3-8 carbon atoms, for example, isopropyl, isobutyl, greg-butyl, isoamyl, gret-amyl or isohexyl, cycloalkyl with 3-7 carbon atoms, for example cyclopropyl, cyclobutyl, shchiklolentil, diklogeksil or cycloheptyl, or alkenyl with 3-6 carbon atoms, such as allyl, metal or crotyl, and the MdryT urea and alkanolamine radicals are related to each other in the ortho, meta or Para position, as well as their salts of physiologically compatible acids, such as chlorine hydrogen, hydrobromic, iodine, sulfuric, nitric, phosphoric, acetic, dichloroacetic, propionic, benzyl, salicylic, oxalic, malonic, adipic, maleic, fumaric, wine, lemon, asorbic, oxalic, malonic, adipic, malic, fumaric, wine, lemon, or asorbic, oxalic, malonic, adipic, malic, fumaric, wine, lemon, or and mixtures thereof.

A preferred method for the preparation of a compound of general formula (I) is that the ureidophenyl derivative of the general formula

N- /

 / 0-SNg-CH-Shg-1 p-A1

B

0-A,

No

where R2 has the indicated meanings;

AI and A2 are hydrolytic kiloxycarbonyl group, for example, benzyloxycarbonyl group, or hydrogenolitically cleavable protective group, such as a-aralkyl group, for example benzyl group, or alkoxycarbonyl group, for example Imer of tertbutoxycarbonylgrull, or cycloalkoxycar0-CH., - CH (OH) -CHj-W-Bj

bonilg group, narylmer cyclodenyloxycarbonyl group, ETI a-aralkyloxycarbonyl group, nalimer benzyloxycarbonyl group; or AI and A2 together - a hydrolytically cleavable protective group, such as carbonyl-,

oxalyl, alkylidene, or cycloalkylidenegroup;

BI and BS are hydrogen or a hydrolytically cleavable protecting group, for example, an aliphatic or aromatic acyl group,

or B and B2 together-hydrolytically cleavable protective group, such as oxaligroup; subjected to interaction with an alkylating agent of the General formula

Ri-X (III),

where RI has the indicated meanings;

X is a halogen, an alkyl sulfate residue or a sulfonic acid residue, for example benzenesulfonyl or toluenesulfonyl, and the protecting groups present are removed in a known manner.

If AI is adyl, then the compounds of general formula (II) can be used in the form of alkali salts.

Acid neutralizers, such as alkali metal carbonates, are used in the product. The reaction is carried out in the presence of an inert diluent or solvent, for example ethanol, is accelerated or completed by supplying

heat from outside or increased pressure.

The hydrogenolysis of the protecting groups is carried out by catalytic hydrogenation, for example, in the presence of latina, palladium or

Rene nickel in an inert diluent or solvent suitable for the selected catalyst, for example in alcohol, in an aqueous solution of alcohol, dioxane or glacial acetic acid. Hydrogenolysis is accelerated or carried out.

more fully by introducing a co-catalyst, for example, hydrochloric or oxalic acid, if hydrogenated catalysts are used based on noble metals. The hydrolysis of the protective groups is carried out in a known manner in an acidic or alkaline medium. Depending on the substituents of the compounds of the reactionone mixture, the temperature and the solvent vary.

The compounds of the general formula (I) obtained by reaction with the indicated acids can be treated in their salts.

The resulting salts of the compound of general formula (I) with inorganic bases

can be converted to loose compounds.

The resulting racemic compounds of general formula (I) can be separated into oltic isomers by known methods.

Optically active compounds of the general formula (I) can also be prepared using optically active starting materials in the reaction.

Example 1. 1.8 g of (3-cyclo-1-hexylureido) phenoxy -2-hydroxy-3-aminopropane hydrochloride, 72 ml of isopropanol, 5.4 g of isopropyl bromide, 3.6 g of potassium carbonate, and 0.4 ir of potassium iodide are stirred for 16 h. at 70 ° C. Then 60 ml of water and 5 ml of 1N are added. sodium alkali, distilled alcohol and excess isolate bromide and filter the target product, so pl. 156-159 ° C (isopropanol).

Analogously to Example 1, the following compounds are prepared.

ConnectionT. pl., ° C

1- (4-ureidophenoxy) -2oxy-3-isopropylaminopropane141, 5-142,5

1- (4-Ureidophenoxy) -2-hydroxy-3-gregbutylaminopropane 207 hydrochloride (decomp.) (3-methylureido) phenoxy -2-hydroxy-3-isopropylaminopropane 154-156 (3-ethylureido) phenoxy -2-hydroxy- H-treg-butylaminopropane 122-124 (3-cyclohexylureido) -phenoxy -2-hydroxy-Zizopropylaminopropan, 157-160

 (3-methylureido) -phenoxy -2-hydroxy-3-greg-butylaminopropane 140-143

 - (3-cyclo: hexylureido) -phenoxy -2-hydroxy-3 greg-butylaminopropane 443-145 (3-lere-1hexylureido) phenoxy -2-hydroxy-3-isopropylaminoprolan 146-149

(3-isoprolylureido) phenoxy -2-hydroxy-3-isolopylaminopropane 154-156

 (3-allylureido) -phenoxy -2-hydroxy-3-isopropylaminolpropane145-147

(3 - sec-butylureido) -phenoxy - 2 - hydroxy - 3isololylaminoprolane 141.5-143 1- 4 - (3 -isoamylureido) phenoxy -2-hydroxy-3-isololylaminopropane124-127

1 - 4 - (3 - crotyureido) phenoxy -2-hydroxy-3-isopropylaminopropane140, 5-143.5

(3-cyclopentylureido) -phenoxy-2-hydroxy-3isolropylaminoprolane 157,5-il60 1 - 4- (3-cycloheptylureido) -phenoxy -2-hydroxy-3isolropylaminoprol145-148

(3-cyclopropyl-reido) -phenoxy-2-hydroxy-3-isopropylaminolrolane

1- | 4- (3-1hexen-2-Elureido) -phenoxy -2-hydroxy-3-isoprolylaminopropane

1-, 2- (3-diclohexylureido) -phenoxy-2-hydroxy-3greg-butylaminopropane (o-cyclo, hexylureido) -phenoxy -2-oxy-3gr-: butylaminopropane 1 (3-cyclohexylureido) -phenoxy-oxy - 3lere-hexylaminopropane 1- | 4 - (3-cyclohexylureido) -phenoxy -2-hydroxy-3-methylamine propane

 (3-cyclohexylureido) -phenoxy-2-hydroxy-3ler-butylaminopropane 1- | 4- (3-diclohexylureido) -phenoxy -2-hydroxy-3-CYCL01hexylamine-propane

 - (3-cyclohexylureido) -phenoxy -2-hydroxy-3-v-butylaminopropane 1-4- (3-cyclo; hexylureido) phenoxy -2-hydroxy-3-isoamylaminoprol

1 - 4- (3-cyclo-1hexyl reido) phenoxy -2 -oxy-3 crotylamine-propane

1 - 4- (3-cyclohexylure 11 to) phenoxy - 2 - oxy - 3cyclopentylaminopropane 1 - 4- (3, cyclohexylureido) phenoxy - 2 - hydroxy-3 cycloheptylaminolrolane 1 - 4- (3-cyclohexylureido) - phenoxy -2 - hydroxy - 3 (1,1,3,3-tetramethyl butyl) aminopropane

1 - 4- (3-cyclohexylureido) -phenoxy -2-hydroxy-Zchhexen-2-ylaminolropane

 - (3-Dikloheksilureido) -phenoxy -2 - hydroxy - 3cyclopropylaminopropane 1 (3-ethylureido) -phenoxy -2-hydroxy-3 - alkylaminopropane

EXAMPLE 2 A mixture of 1 g of ureido) phenoxy) - 2-oxylrolane, 0.4 g of benzoic cananol is heated to a light solution which boils. When given benzoate (Z-cyclooxy -2-hydroxy-3-treg-butyl 194-198 ° C.

In a similar way, tartaric acid. Instead of 0.4 ty, you get a neutral cyclotexylureido) pheno-butylaminoprolane, t. Pl.