KR860007219A - Process for preparing sulfonylaminoethyl compound - Google Patents

Abstract

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Description

Process for preparing sulfonylaminoethyl compound

Since this is an open matter, no full text was included.

Claims (24)

(a) acylating a compound of formula (II) with a phenylsulfonic acid derivative of formula (III) and then separating the protecting group used, or (b) removing a protecting group from a compound of formula (IV) Hydrolysis, hydrolysis or pyrolytic separation to prepare a compound of formula (I) wherein E is a hydroxycarbonyl group bonded through an alkylene or alkenylene group, or (c) a compound of formula (V) The compound is acylated with a compound of formula (VI) or an anhydride thereof in the presence of Lewis acid, and then optionally separating the protecting group used so that E adjacent to group B contains a carbonyl group of formula (I). Preparing a compound or (d) reducing the compound of formula (iii) to produce a compound of formula (I) wherein E adjacent to group B contains a hydroxymethylene group, or (e) Hydrogenated to prepare a compound of formula (I) wherein E is a saturated group; (f) decarboxylation of the compound of formula (iii) optionally prepared in the reaction mixture to prepare a compound of formula (I) wherein E is a hydroxycarbonyl group bonded through a saturated alkylene group, or ( g) reacting a compound of formula (X) or a reactive derivative thereof with hydrazine to prepare a compound of formula (I) wherein E is a pyridazinone ring, or (h) a compound of formula (XI) Reaction with a compound of formula (I), optionally followed by isolation of the protecting group used, and if an ester of formula (I) is obtained, conversion to the corresponding carboxylic acid yields a compound of formula (I) Or (i) reacting acetophenone of general formula (XIII) with a dialkyl carbonate in the presence of a base, and then optionally if the compound of general formula (I) obtained contains a carboxy group, Or addition salts with organic bases, More particularly if the sulfonylaminoethyl compound of formula (I) and E contain a hydroxycarbonyl group or are hydroxycarbonyl groups, characterized by conversion to pharmaceutically useful physiologically acceptable addition salts, A process for preparing salts of inorganic or organic bases of the general formula (I) compound. Wherein R ₁ is a phenyl group optionally mono- or di-substituted with a methyl group or a halogen group where the substituents may be the same or different, a biphenylyl group optionally substituted with a halogen atom, or naphthyl, pyri Dill or thienyl group; R ₂ is a hydrogen atom or a methyl group; A is a methylene or methyleneoxy group wherein the oxygen atom is bonded to an adjacent group B; B is phenylene or naphthylene group; E is a hydroxycarbonyl or alkoxycarbonyl group bonded through a straight or branched alkylene group of C ₂ to C ₅ or through an alkenylene group of C ₃ to C ₅ , wherein the foregoing should be bonded to group B The methylene group in one alkylene or alkenylene group is replaced by a hydroxy-methylene or carbonyl group, and an alkoxy moiety which may be substituted by C ₁ to C ₅ alkoxy group in 2- or 3-position is 1 to 3 4,5-dihydro-pyridazin-3-one-6-yl or pyridazine- optionally substituted with 1 to 2 alkyl groups having 1 to 3 carbon atoms in the carbon structure). 3-on-6-yl group; In general formula (II), the hydroxy group of group E may be protected with a protecting group (eg alkoxy or benzyloxy group) which can be removed by hydrolysis or hydrogenolysis; X is a nucleophilic leaving group; E ₁ has the same meaning as E above, but the carboxy group is protected by a protecting group which can be removed by hydrolysis, pyrolysis or hydrolysis, constitutes a functional derivative of the carboxy group, and / or is a group E ₁ Contains a hydroxy group protected with a protecting group; E ₂ has the same meaning as E as defined above, but E adjacent to Y must contain a carbonyl group, while at the same time the hydroxycarbonyl group present is protected that can be removed by hydrolysis or hydrogenolysis. May be protected by a group such as an alkoxy or benzyl group; Y is a nucleophilic leaving group; E ₂ has the same meaning as E defined above, but E must contain a carbonyl group; E ₄ is one of the unsaturated groups mentioned in the definition of E above; E ₅ at the same carbon atom is two hydroxycarbonyl groups bonded through a straight or branched chain alkylene group of C ₁ to C ₅ , wherein the methylene group of group E ₅ which is bound to group B is hydroxy Substituted by oxymethylene or carbonyl group; R ₆ and R ₇ may be the same or different and each independently represent a hydrogen atom or an alkyl group, wherein R ₆ and R ₇ together may contain a total of 1 to 3 carbons; W is a hydrogen atom or they together represent another bond; Z is a nucleophilic leaving group (eg halogen atom or sulfonyloxy group); In formula (XII), the hydroxy group present in group B may be protected by a protecting group which can be removed by hydrolysis (eg, alkoxy or benzyloxy group); R ₈ is a hydrogen atom or a methyl or ethyl group. The compound of claim 1, wherein R ₁ is a methyl group or a phenyl group optionally substituted with fluorine, chlorine or bromine atom, a 4-biphenyl group optionally substituted with fluorine or chlorine atom, or naphthyl, pyridyl or thienyl group; R ₂ is a hydrogen atom or a methyl group; A is a methylene or methyleneoxy group wherein the oxygen atom is bonded to an adjacent group B; B is 1,4-phenylene or 1,4-naphthylene group; Hydroxycarbonyl or alkoxycarbons having 2 or 3 total carbon atoms, wherein E is bonded through a straight or branched alkylene group of C ₂ to C ₄ or through a straight or branched alkenylene group of C ₃ to C ₄ Nyl group (wherein in the above-described alkylene or alkenylene group to be bonded to group B, one methylene group is replaced by hydroxymethylene or carbonyl group, and the ethoxycarbonyl group is replaced by methoxy group in 2-position). But may not be a hydroxycarbonyl-methylenecarbonyl group optionally substituted with a methyl or ethyl group at the α-position, or E is a 4,5- optionally substituted with a methyl group at the 5-position Sulfonylaminoethyl compounds of formula (I), which may be dihydro-pyridazin-3-one-6-yl or pyridazin-3-one-6-yl groups, and E contains a hydroxycarbonyl group Or a hydroxycarbonyl group, Bansik (I) Method for preparing inorganic or salts with an organic base compound. The compound of claim 1, wherein R ₁ is a phenyl group optionally substituted with a chlorine atom or a methyl group; R ₂ is a hydrogen atom; A is methylene or methyleneoxy group; B is a 1,4-phenylene group; 2 or 3 hydroxycarbonyl or alkoxycarbonyl groups having a total of 2 or 3 carbon atoms bonded through an E-group n-propylene group, in which the methylene group is a hydroxymethylene or carbonyl group. Alternatively, the ethoxycarbonyl group may be substituted with a methoxy group at the 2-position) or 4,5-dihydro-pyridazin-3-one-6- optionally substituted with a methyl group at the 5-position Preparation of salts of inorganic or organic bases of the general formula (I) compound when the sulfonylaminoethyl compound of general formula (I) which is one group and E contains a hydroxycarbonyl group or a hydroxycarbonyl group How to. The process according to claim 1, wherein 3- [4- (2-benzenesulfonylaminoethyl) -benzoyl] -propionic acid and its addition salt with inorganic base are prepared. The process of claim 1, wherein 6- [4- (2-benzoylsulfonylaminoethyl) -phenyl] -4,5-dihydro-pyridazin- (2H) -3-one is prepared. The method according to any one of claims 1 to 4, wherein a physiologically acceptable addition salt of the general formula (I) compound with an inorganic or organic base is prepared. The process of claim 1 wherein the reaction is carried out in a solvent. 8. Process according to claim 1 (a) or 7, wherein the reaction is carried out in the presence of an acid binder. Process according to claim 1, 7 or 8, wherein the reaction is carried out at 0 to 50 ° C., preferably at ambient temperature. The process according to claim 1 (b) or 7, wherein the protecting group is separated by sublimation in the presence of an acid or a base at a temperature of -10 to 120 ° C. The process according to claim 1 or 7, wherein the nitrile or aminocarbonyl group is converted into a carboxyl group using nitrite in the presence of an acid at a temperature of 0 to 50 ° C. Process according to claim 1 or 7, wherein the nitrile or aminocarbonyl group is converted to a carboxyl group using 100% phosphoric acid at 100 to 180 ° C, preferably 120 to 160 ° C. The process according to claim 1 or 7, wherein the benzyloxy group is separated by hydrogenolysis in the presence of a hydrogenation catalyst at a temperature of 0 to 50 ° C. Process according to claim 1 or 7, wherein the tert-butyloxycarbonyl group is separated by pyrolysis in the presence of an acid at the boiling point of the solvent used, preferably at a temperature of 40 to 100 ° C. The process according to claim 1 (c) or 7, wherein the reaction is carried out in the presence of Lewis acids such as aluminum chloride, boron trifluoride and zinc chloride. Process according to claim 1, 7 or 15, wherein the reaction is carried out at 0 to 50 ° C., preferably at ambient temperature. 8. Process according to claim 1 or 7, wherein the reduction is carried out in the presence of hydrogen or metal hydride to be catalytically activated. Process according to claim 1, 7 or 17, wherein the reaction is carried out at a temperature of from 0 to 100 ° C, preferably from 20 to 80 ° C. Process according to claim 1 (e) or 7, wherein the reduction is carried out in the presence of catalytically activated hydrogen or generator hydrogen. Process according to claim (e), 7 or 19, wherein the hydrogenation is carried out at 0 to 50 ° C., preferably at ambient temperature. Process according to claim 1 (f) or 7, wherein the decarboxylation is carried out in the presence of an acid at a boiling point of the reaction mixture, preferably at a temperature of 80 to 100 ° C. Process according to claim 1 (g) or 7, wherein the reaction is carried out at 0 to 200 ° C, preferably at the boiling point of the reaction mixture. Process according to claim 1 or 7, wherein the reaction is carried out in the presence of anhydrous base at a temperature of 25 to 100 ° C, preferably 40 to 80 ° C. Process according to claim 1 or 7, wherein the reaction is carried out in the presence of potassium tert-butoxide at a temperature of 50 to 150 ° C, preferably 75 to 100 ° C. ※ Note: The disclosure is based on the initial application.