KR850003403A - Method for preparing phenoxy propanol amine - Google Patents

Abstract

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Description

Method for preparing phenoxy propanol amine

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Claims (14)

The epoxide of formula (II) or β-ketohalide of formula (III) is reacted with the primary amine of formula (IV) or the secondary amine of formula (V), and X ^1- Reduce the C (O)-or X ² -C (O) -group to the X ¹ -CHOH- or X ² -CHOH- group and, if necessary, X ¹ , X ² , Y or Z of the compound of formula (I) Functionally modify the reactive substituents present in the group, and if necessary, alkynylated or phenalkanoylated the hydroxy group present in the diol of general formula (I), and if necessary, a compound of general formula (I) A process for preparing phenoxypropanolamine of formula (I) and its physiologically suitable salts, characterized by conversion. Wherein n is 1 or 2, R is hydrogen, lower-alkanoyl or phenyl-lower-alkanoyl, X ¹ is phenoxymethyl optionally mono-fluorinated or mono-chloroated in the ortho-position, X ² is lower-alkyl, phenoxymethyl optionally mono-fluorinated or mono-chloro in the ortho-position or phenyl optionally monosubstituted by fluorine, chlorine, trfluoromethyl or lower alkoxy, Y is hydrogen or Methyl, Z is the general formula Wherein R ¹ is optionally N-mono-lower-alkylated or N-di-mono-lower-alkylated aminomethyl, or residues -C (O) R ² , -C (R ³ ) = CH- (CH ₂ ) _m -C (O) R ² , -C (H, R ³ )-(CH ₂ ) _{m + 1} C (O) R ² , -O (H, R ³ )-(CH ₂ ) _p -OH or -C (R ³ ) = CH- (CH ₃ ) = CH-COOH ₃ , R ¹¹ is hydroxy, lower-alkoxy, lower-alkanoyloxy, sulfoyl or fluorine, chlorine, trfluoro Benzyloxy or phenoxy optionally ring-substituted by methyl, lower alkyl or lower-alkoxy, or groups R ¹ , -O- (CH ₂ ) _q -OH.-O- (CH ₂ ) _q -COOR ⁴ .- O- (CH ₂ ) _q -O (CH ₂ ) _t -R ⁵ or -O- (CH ₂ ) _v R ² is hydroxy, lower-alkyl, lower-alkoxy, dimethylaminoethoxy, lower-alkoxycarbonylethyl or optionally mono-loweralkylated or di-loweralkylated amino, R ³ is hydrogen or methyl and R ⁴ is lower-alkyl, R ⁵ is phenyl optionally para-substituted by hydrogen, lower alkyl or chlorine, fluorine, trifluoromethyl, lower-alkyl or lower-alkoxy, R ⁶ is phenyl optionally para-substituted by lower alkyl or fluorine, chlorine, lower-alkyl or lower-alkoxy, m and f are integers from 0 to 6, v is an integer from 2 to 4, q and t are An integer from 1 to 6, Hal is halogen, one of the X ³ and X ⁴ groups is the X ¹ group and the other is the X ² group, wherein the compound of formula (III) or (III) is When reacted with a compound of X ³ is a X ¹ group. An epoxide of formula (II-1) or β-ketohalide of formula (III-1) is reacted with an amine of formula (IV), and the X ¹ -C (O)-group present in the obtained compound Reduced to an X ¹ -CHOH- group, or a compound of one of Formulas (VI), (VII), (VIII), (IX) and (X), if necessary, of Formula (V-1) Functionally modify the reactive substituents present on the X ¹ , Y or Z groups of the compound, and if necessary, alkanoylated or penalkanoylated hydroxy groups present in the alcohols of formula (V-1), A process for preparing phenoxypropanolamine of the general formula (V-1) and its physiologically suitable salts, characterized by converting a compound of formula (V-1) to a salt thereof. Wherein X ¹ , R, Y, Z and n are as defined in claim 1. The substituent R ¹¹ in the phenyl group Z is hydroxy, lower-alkanoyloxy, sulfamoyl or group R ¹ , -O- (CH ₂ ) _q -OH or -O- (CH ₂ ) _q -O (CH ₂ ) _t -R ⁵ , R ⁵ is hydrogen, lower-alkyl or phenyl and the remaining symbols are as defined in claim 1 or 2. The method of claim 1, wherein R is hydrogen. The compound according to any one of claims 1 to 4, wherein X ¹ is phenoxymethyl, X ² is phenoxymethyl or phenyl, in particular the C-atom bonded to the phenoxymethyl residue X ¹ or X ² has an X-configuration A C-atom having a phenyl residue R ² . Process according to any of the preceding claims, wherein the C-atom wherein Y is bonded to methyl, in particular methyl residue Y, has an R-configuration. The process according to claim 1, wherein Z is thienyl substituted by phenyl or carbamoyl, methoxycarbonyl or 2- (ethoxy or methoxy) -carbonyl-1-methylvinyl. The process according to any one of claims 1 to 6, wherein Z is phenyl substituted by 6-hydroxyhexoxy, 2-phenethoxy-2-ethoxy or (ethoxy or methoxy) -carbonylethoxy. The method according to any one of claims 2 to 6, wherein Z is p-hydroxyphenyl. The compound of any one of claims 1 to 8, wherein R is hydrogen, X ¹ is phenoxymethyl, X ² is phenoxymethyl or phenyl, Y is methyl, Z is phenyl or carbamoyl, methoxycarbonyl or Thienyl or 6-hydroxyhexoxy, 2-phenethoxy-2-ethoxy or (ethoxy or methoxy)-substituted by 2- (ethoxy or methoxy) -carbonyl-1-methylvinyl And phenyl substituted by carbonylmethoxy. The method according to any one of claims 2 to 6 and 9, wherein R is hydrogen, X ¹ is phenoxymethyl, Y is methyl and Z is p-hydroxyphenyl. The C-atom of any one of claims 1 to 11, wherein the C-atom bonded to the methyl residue Y has an R-configuration, the C-atom bonded to the phenoxymethyl residue X ¹ or X ² has an S-configuration, and the phenyl residue X ² To a C-atom having an R-array. The process according to claim 1 or 2, characterized in that 1,1 '-[[(R) -α-methyl-p- [2- (phenethoxy) ethoxy] is characterized by using a correspondingly substituted starting material. Phenethyl] imino] bis [(S) -3-phenoxy-2propane] or (S) -1-[[(R)]-α-methyl-p- (2- (ethoxy) ethoxy ] Phenethyl] amino] -3-phenoxypropanol. 3. Methyl (E) -p-[[(R) -2- [bis- (RS) -2-hydroxy-3, according to claim 1 or 2, characterized in that a correspondingly substituted starting material is used. -Phenoxypropyl] amino] propyl] -β-methyl-cinnamate, to methyl p-[(R) -2- [bis- (RS) -2-hydroxy-3-phenoxypropyl] amino] propyl complex , 6- [p- (R)-[bis (S) -2-hydroxy-3-phenoxypropyl] amino] propyl] phenoxy-1-hexanol, methyl 2- [p-[(2- [[(RS) -2-hydroxy-3-phenoxypropyl] amino] propyl] acetate, methyl (E) -p-[(R) -2-[[(RS) -2-hydroxy-3- Phenoxypropyl] amino] propyl-β-methyl-cinnamate, p-[(R) -3-[[(RS) -2-hydroxy-3-phenoxypropyl] amino] butyl] benzamide, methyl p -[(R) -2-[[(RS) -2-hydroxy-3-phenoxypropyl] amino] propyl] benzoate, p-[(R) -2-[[(S) -2-hydroxy Oxy-3-phenoxypropyl] amino] propyl] phenol or 6- [p- (R) -2-[[(RS) -hydroxy-3-phenoxypropyl] amino] propyl] phenoxy To prepare hexanol. ※ Note: The disclosure is based on the initial application.