Patent GB-1069345-A (GB)
Title: New alkanolamine derivatives
Inventor: CROWTHER ALBERT FREDERICK
IPC: C07D303/22
Filed: 1962-12-11
Abstract: The invention comprises racemic alkanolamine derivatives of formula <FORM:1069345/C2/1> wherein R1, R3 and R4 represent hydrogen, R2 the n-propyl radical and the radical A represents 3-tolyl, 2,5-dichlorophenyl or 3-methoxyphenyl; or R1 represents hydrogen or an alkyl radical (not more than 5 C), R2 a branched chain alkyl or hydroxyalkyl radical (not more than 10 C), or for an alkyl radical (not more than 5 C), or for a cycloalkyl or alkenyl radical (not more than 15 C) and optionally substituted by one or more halogen atoms, hydroxy radicals, or alkoxy radicals (not more than 5 C), R3 and R4 which may be the same or different represent hydrogen or alkyl radicals (not more than 5 C) and the benzene ring A has a single substituent in the 3- or 4-position only which is an halogen atom, an alkyl, alkoxy, alkylthio, alkanoyl, aralkanoyl, aroyl, aryl, aryloxy, alkylaryloxy, arylthio, arylsulphonyl, arylamino, aralkyl, aralkoxy, or alkenyl radicals (each containing not more than 10 C), a halogenoalkyl radical (not more than 5 C) or an hydroxy or nitro radical, or the benzene ring A bears a single substituent in the 2-position only, which is an hydroxy, nitro, iodo, alkanoyl, aralkanoyl, aroyl, aryl, aryloxy, alkylaryloxy, arylthio, arylsulphonyl, arylamino, aralkyl or aralkoxy substituent (each containing not more than 10 carbon atoms, or the benzene ring A bears two, three, four, or five substituents which are selected from the radicals given for the 3- or 4-position only; the carboxylic esters and the salts thereof, which derivatives possess b -adrenergic blocking activity and are useful in the treatment or prophylaxis of coronary artery disease. Certain listed compounds are excluded from compounds of the above formula and examples of suitable radicals are given.  The alkanolamine derivatives are prepared by reacting a halogeno compound <FORM:1069345/C2/2> where Z stands for a Cl, Br or I atom with an amine NHR1R2; by reacting an epoxide <FORM:1069345/C2/3> with an amine NHR1R2; by reacting a compound <FORM:1069345/C2/4> with ZCH.R3.CHOH.CHR4.NR1R2 or <FORM:1069345/C2/5> by the hydrogenolysis of <FORM:1069345/C2/6> where R stands for an hydrogenolysable radical e.g. benzyl and R6 a carbonyl, hydroxymethylene or CHOR1, where R7 represents an hydrogenolysable radical; by reacting an amino derivative <FORM:1069345/C2/7> with a carbonyl compound R8.CO.R9, where R8 represents hydrogen, or alkyl (not more than 4 C) and R9 a branched chain alkyl or hydroxyalkyl or substituted alkyl or aralkyl radical; by the hydrogenolysis of a compound <FORM:1069345/C2/8> where the benzene ring A bears a substituent -OR7 to form compounds in which A bears an hydroxy substituent; by the oxidation of <FORM:1069345/C2/9> wherein A bears an arylthio substituent to produce a derivative wherein the ring A bears an arylsulphonyl substituent.  The carboxylic esters may be prepared by reacting the alkanolamine derivative or salt thereof with an acylating agent.  Examples describe the preparation of 1 - (2,3 - dimethylphenoxy) - 3 - isopropylamino-2 - propanol and many listed bases and salts, 1-(3 - ethoxyphenoxy) - 3 - isopropylamino - 2-propanol oxalate, 1 - isopropylamino - 3 - (3-tolyloxy) - 2 - propanol, 1 - (4 - benzyloxyphenoxy) - 3 - isopropylamino - 2 - propanol, 1-isopropyl - amino - 3 - pentafluorophenoxy - 2-propanol and many other compounds. Suitable esters mentioned are derived from saturated or unsaturated aliphatic carboxylic acids (not more than 20 C) e.g. acetic, palmitic, stearic or oleic acids, or aromatic e.g. benzoic acid and salts may be hydrochlorides, hydrobromides, phosphates or sulphates or oxalates, lactates, tartrates, acetates, salicylates, citrates, benzoates, b  - naphthoates, adipates or 1,11-methylene - bis (2 - hydroxy - 3 - naphthoates) or derived from acidic synthetic resins e.g. sulphonated polystyrene resins.ALSO:Acid-addition salts of acidic synthetic resins' e.g sulphonated polystyrene with racemic alkanolamine derivatives of formula <FORM:1069345/C3/1> wherein R1, R3 and R4 represent hydrogen, R2 represents an n-propyl radical and the benzene radical (A) stands for the 3-tolyl, 2,5-dichlorophenyl or 3-methoxy phenyl radical; or wherein R1 represents hydrogen or an alkyl radical (not more than 5 C), R2 a branched chain alkyl or hydroxyalkyl (not more than 10 C), or for an alkyl (not more than 10 C) substituted by alkoxy (not more than 5 C), or for a cycloalkyl or alkenyl radical (not more than 5 C) or for branched chain aralkyl radical (not more than 15 C) which may optionally be substituted by one or more halogen atoms, hydroxy radicals or alkoxy radicals (not more than 5 C), R3 and R4 which may be the same or different, represent hydrogen or for alkyl radicals (not more than 5 C) and the benzene ring (A) bears a single substituent in the 3- or 4-position only which is a halogen atom, an alkyl, alkoxy, alkylthio, alkanoyl, aralkanoyl, aroyl, aryl, aryloxy, alkylaryloxy, arylthio, arylsulphonyl, arylamino, aralkyl, aralkoxy or alkenyl radical (not more than 10 C), a halogenoalkyl radical (not more than 5 C) or a hydroxy or nitro radical, or the benzene ring (A) bears a single substituent in the 2-position only which is a hydroxy, nitro, or iodo substituent or an alkanoyl, aralkanoyl, aroyl, aryl, aryloxy, alkylaryloxy, arylthio, arylsuphonyl, arylamino, aralkyl or aralkoxy substituent (not more than 10 C), or the ring A bears two, three, four or five substituents selected from the values above for the single substituent in the 3- or 4-position (see Division C2), have b -adrenergic blocking activity.  An example describes the addition of a suspension of sulphonated polystyrene resin to a solution of 1 part of 1-isopropylamino-3-(3-tolyloxy)-2-propanol hydrochloride to form a complex salt.