KR830007505A - Process for preparing phenylalkylamine - Google Patents

Abstract

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Description

Process for preparing phenylalkylamine

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

Claims (26)

a) reducing the compound of formula (II), or b) reacting a carbonyl compound of formula (III) or an aldehyde hydrate thereof optionally prepared in the reaction mixture with an amine and a reducing agent of formula (IV), or c) removing one or more protective residues of formula (V), or d) degenerated the compound of formula (VI) to prepare a compound of formula (I) wherein one of the R ₂ or R ₃ residues represents a hydrogen atom, or e) alkylating a compound of formula (VII), or f) R ₁ represents an amino group substituted with an alkanoyl group having 1 to 3 carbon atoms or an alkoxycarbonyl group having 2 to 4 carbon atoms, and R ₅ is a compound of formula (I) which does not represent a hydrogen atom. In order to do this, the compound of the formula (VIII) is alkylated with a compound of the formula (VIII), g) in order to prepare a compound of formula (I) wherein D represents a sulfinyl or sulfonyl group, h) To prepare a compound of formula (I) wherein D represents an oxygen or sulfur atom and R ₅ does not represent a hydrogen atom, the compound of formula (XI) may be a compound of formula (XII) or an alkali salt thereof or The compound of general formula (I) containing 1,2 or 3 optically active carbon atoms thus obtained is reacted with an alkaline earth metal salt, and subsequently separated into its optically active colon, its diastereomeric racemate and its optical colon. And / or thus converting the obtained compound of formula (I) into a salt with its physiologically acceptable inorganic or organic acid. In the above meal R ₁ is an amino group, alkylamino or dialkylamino group optionally substituted with a hydroxy group, an alkanoyl group having 1 to 3 carbon atoms or an alkoxycarbonyl group having 2 to 4 carbon atoms, where each alkyl moiety is a carbon atom 1 To 3, each of which may be substituted with a phenyl group). R ₂ and R ₃ are the same or different and represent a halogen atom, trifluoromethyl, cyano or nitro group or one of R ₂ and R ₃ represents a hydrogen atom, R ₄ represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, R ₅ represents a hydrogen atom, a linear or branched alkyl group of 1 to 4 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, an alkenyl group of 2 to 5 carbon atoms, or an aralkyl group of 7 to 10 carbon atoms, A represents methylene, ethylene or hydroxy methylene group, B is the following general formula or Represents a group of, R ₆ represents hydrogen or a halogen atom, a hydroxy group, an alkoxy group having 1 to 3 carbon atoms optionally substituted with a phenyl group, an alkylsulphenyl or alkylsulfinyl group having 1 to 3 carbon atoms each, R ₇ represents a hydrogen atom, a hydroxy group or an alkoxy group having 1 to 3 carbon atoms, or R ₆ and R ₇ together represent a methylenedioxy group, R ₈ represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, D represents an oxygen or sulfur atom, sulfinyl or sulfonyl group, n represents 1 or 2 E represents a straight chain alkylene group of 3 to 5 carbon atoms optionally substituted with 1 or 2 alkyl groups of 1 to 3 carbon atoms each, provided that A represents a methylene or ethylene group and / or R ₁ represents a carbon atom Amino groups, hydroxy, alkylamino or dialkylamino groups substituted with 1 to 3 alkanoyl groups or 2 to 4 alkoxycapnyl groups, wherein the alkyl moieties may each contain 1 to 3 carbon atoms Each of which may be substituted by a phenyl group) and / or R ₂ represents a trifluoromethyl, cyano or nitro group, and / or R ₃ represents a fluorine atom, and / or R ₄ represents carbon atom 1-3 alkyl denotes a group, and / or R ₅ is alkyl of 1 to 4 carbon atoms group, the carbon atom 3 to 6 cycloalkyl groups, the carbon atoms 2 to 5 alkenyl group, or It wishes chair represents the 7 to 10 aralkyl groups, and or R _6, if represent fluorine or a discount atoms, carbon atoms, each with 1 to 3 alkyl sulfonic phenyl or alkylsulfonyl group represents an ethylene group, or A is a methylene group In the case of Also represents a group of wherein R ₉ represents an alkyl group of from 1 to 3 carbon atoms, X represents a group of the following general formula, or Wherein R ₄ is as described above, acyl represents an organic acyl group, Z represents a group that can be removed by reduction, K represents oxygen with hydrogen adjacent to K located in the alkyl moiety of residue L (ie hydrogen adjacent to K located in alkyl moiety in residue L is replaced by a single bond in a carbon-oxygen double bond) L is as defined in B or excluding hydrogen atoms, or as defined in R ₅ or represents a group of the general formula Wherein R ₁ to R ₄ are as described above and A 'represents a carbonyl, methylene or ethylene group. M and Q are different from each other, as described above in B and R ₅ , or one of the residues M or Q represents a group of the general formula Wherein R ₁ to R ₄ and A are as described above R ₁ ′ represents a hydroxy or amino group as described above for R ₁ or protected with a protecting moiety, A 'represents a hydroxy methylene group as described above in A or protected with a protective moiety, R ₅ ′ are the same as described above for R ₅ or represent an amino group protecting moiety, B 'is as described above in B or represents a group of the following general formula. or At this time R ⁸ , D, E and n are as described above, R ₆ ′ and R ₇ ′ are the same or different, Or a hydroxy group as described above for R ₆ and R ₇ or protected with a protecting moiety; At least one of the residues R ₁ ′, _A ′, R ₅ ′ and / or B ′ should contain one of the abovementioned protective residues and Hal represents a chlorine, bromine or iodine atom, R _{5 '} is the same as described above for R ₅ or represents a hydrogen atom, B 'is as described above in B, and when R _5' does not represent a hydrogen atom, at least one of R ₆ or R ₇ residues must represent hydrogen or R ₁ is optionally substituted with an alkyl group having 1 to 3 carbon atoms. To the amino group, wherein the alkyl group may be optionally substituted with phenol residues, R ₁₀ represents a hydrogen atom, a methyl or ethyl group or an alkoxy group having 1 to 3 carbon atoms, Y represents a nucleophilic substitutable group, m represents 0 or 1, V represents a nucleophilic substitutable group, A 'represents a methylene or ethylene group, D 'represents an oxygen or sulfur atom. The process according to claim 1 a) to d), g) or h), wherein the reaction is carried out in a solvent. The process according to claim 1 a) or 2, wherein the reduction reaction is carried out with aluminum isopropylate in the presence of a hydride, primary or secondary alcohol, catalytically activated donor or generator hydrogen. The process according to claim 1 a), 2 or 3, wherein the reaction is carried out at -20 ° C to the boiling temperature of the reaction mixture, for example -20 to 100 ° C. The metal complex hydride, aluminum isopropylate, catalytically activated according to any one of claims 1 to 6, in which A represents a compound of general formula (I) wherein A represents a hydroxy methylene group. To reduced hydrogen or generator hydrogen. Sodium borohydride, sodium cyanoborohydride or lithium aluminum hydride according to any one of claims 1 to 4 for preparing a compound of general formula (I) in which A represents methylene or ethylene group. Reduction with a metal complex hydride or pyridine-borane such as lead. The process according to claim 1 b) or 2, wherein a metal complex hydride or catalytically activated hydrogen is used as the reducing agent. The process according to claim 1 b) or 2, wherein formic acid is used as the reducing agent in methylation. The process according to claim 1 b) or 2 to 7, wherein the reaction is carried out at a temperature of -20 to 100 ° C. The process of claim 1 b) or 8 wherein the reaction is carried out at the boiling temperature of the reaction mixture. The process according to claim 1 c) or 2, wherein the acyl group used as the protecting group is removed by hydrolysis with an acid or a base. The process according to claim 1 c) or 2, wherein the benzyl group used as the protecting group is removed by hydrogenolysis. The process according to claim 1 d) or 2, wherein the dehalogenation is carried out with triphenylphosphine, hydrogen in the presence of a hydrogenation catalyst or metal complex hydride. The method according to any one of claims 1 to 2, wherein the dehalogenation is carried out at a temperature of 0 to 150 ° C. The process according to claim 1, wherein the alkylation of the nitrogen atom is carried out with the corresponding alkyl halogenide or alkyl sulfate, the corresponding carbonyl compound and the metal complex hydride or formaldehyde / formic acid. The process according to claim 1, wherein the alkylation of the phenolic hydroxy group is effected with the corresponding alkyl halogenide, alkylsulfate or diazo alkanes. The process according to any one of claims 1 to 15, wherein the reaction is carried out in the presence of a base and a solvent. The process according to any one of claims 1 to 15, wherein the reaction is carried out at a temperature of -10 to 50 ° C. The process according to claim 1, wherein the reaction is carried out in the presence of a base and a solvent. The process of claim 1 f) or 19, wherein the reaction is carried out at a temperature of from 0 to 100 ° C. The process according to claim 1 g) or 2, wherein the oxidation reaction is carried out with an equimolar amount of oxidizing agent to produce a compound of formula (I) wherein D represents a sulfinyl group. The process according to claim 1 or 2, wherein the oxidation reaction is carried out with an excess of oxidizing agent to produce a compound of formula (I) wherein D represents a sulfonyl group. The method according to claim 1, 2, 20 or 22, wherein the oxidation reaction is carried out at a temperature of -80 to 100 ° C. The method of claim 1, wherein the reaction is carried out in the presence of an alkali base. Process according to claim 1 h) or 24, wherein the reaction is carried out at a temperature of -10 to 100 ° C, preferably 0 to 50 ° C. The process according to claim 1 h), 24 or 25, wherein the reaction is carried out in a solvent. ※ Note: The disclosure is based on the initial application.