Patent GB-893088-A (GB)
Title: Improvements in or relating to substituted amines
IPC: C07D211/22
Filed: 1958-04-14
Abstract: <FORM:0893088/IV (b)/1> <FORM:0893088/IV (b)/2> <FORM:0893088/IV (b)/3> <FORM:0893088/IV (b)/4> <FORM:0893088/IV (b)/5> <FORM:0893088/IV (b)/6> <FORM:0893088/IV (b)/7> <FORM:0893088/IV (b)/8> <FORM:0893088/IV (b)/9> <FORM:0893088/IV (b)/100> <FORM:0893088/IV <FORM:0893088/IV (b)/123> <FORM:0893088/IV (b)/134> <FORM:0893088/IV (b)/145> <FORM:0893088/IV (b)/156> <FORM:0893088/IV (b)/167> <FORM:0893088/IV (b)/178> <FORM:0893088/IV (b)/189> wherein R1, R2 and R3 which are the same or different designate hydrogen, a hydroxy group ethanol or other aliphatic alcohol containing 1 to 6 carbon atoms, R4 is hydrogen or a hydroxy group, R5 is hydrogen or an alkyl group, R6 is hydrogen or an alkyl, or aralkyl group and Y is an alkyl-cycloalkylene or alkylene group or R6, Y1 and the nitrogen atom together form a piperidine ring with or without an alkyl group or a hydroxy group etherified with methanol, as substituent therein, or an acid-addition salt thereof and processes for the preparation thereof (a) by reacting a compound of the formula I with one of the compounds of the formula II, i.e. by esterification; (b) by coupling a compound of formula XII with a compound of formula XIII wherein Me is an alkali metal atom; (c) reacting a compound of the formula XV with a compound of the formula XVI wherein X is a chlorine bromine or iodine atom or a keto- or aldehyde-oxygen atom, in the presence of an acid binder when X is halogen; when X is a keto or aldehyde oxygen atom reduction may be effected with hydrogen and a metal catalyst; (d) introducing the group R5 into compounds of the formula XIX by reaction with a dialkyl sulphate or with a compound of the formula R5 Hlg wherein Hlg is bromine or chlorine (e) hydrogenating compounds of the formula XX, e.g. in the presence of platinum or palladium.  The amino-alcohols of the formula I may be obtained by reacting a substituted aralkyl compound of the formula III with an amino alcohol of the formula IV or, alternatively, by reacting a substituted aralkylamine of the formula V with a half-ester-half-acid halide of the formula VI in which Y1 is a branched or unbranched alkylene radical to produce compounds of the formula VII which may be reduced with LiAlH4 to obtain the desired amino alcohol I.  Further methods of making compound I comprise (a) reacting a compound of the formula V with a halogen alcohol of the formula VIII, or a halogen aldehyde or halogen ketone, or ethylene oxide, (b) catalytically reducing a keto or aldehyde-alcohol with amines of the formula V, (c) catalytically hydrogenating the aralkyl ketones or aldehydes of the formula IX in the presence of amino-alcohols of the formula X, (d) converting tetrahydrofurfurylamines of the formula IX with HBr and adding alkali to effect cyclization- Compounds of the formula XII may be obtained by reacting the corresponding alcohols with PCl5, SO2Cl2, POCl3, PBr3 or SO2Br2 or by reacting compounds of the formula V with a compound of the formula XIV.  Compounds of the formula XVI may be obtained (a) by esterifying a compound of the formula II with a divalent alcohol of the formula XVII followed by treatment with a halogenating agent (b) by esterifying a compound of the formula II with a halogen alcohol of the formula VIII, (c) esterifying a compound of the formula XIII with an aliphatic dihalogen compound of the formula XIV, by the esterification of an acid or acid halide of formula II with an aldehyde or keto-alcohol.  Alternatively, the esterification may be effected with a di-alcohol after which the non-esterified alcohol group is oxidised to an aldehyde or keto group.  In another method the keto or aldehyde esters are obtained by esterifying a compound of the formula XIII with a halogen ketone or halogen aldehyde.  The products of the invention may be produced in the form of their salts, e.g. hydrochlorides, hydrobromides, acetates, oxalates, citrates, sulphates and phosphates.  Detailed examples are given.ALSO:Pharmaceutical preparations for reducing the blood pressure comprise a compound having the formula <FORM:0893088/VI/1> or an acid addition salt thereof, in which formula R1, R2 and R3, which are the same or different designate hydrogen, a hydroxy group, or a hydroxy group etherified with methanol, ethanol or other aliphatic alcohol containing 1-6 carbon atoms, R4 designates hydrogen or a hydroxy group, R5 designates hydrogen or an alkyl group, R6 designates hydrogen or an alkyl or aralkyl group and Y designates an alkylcycloalkylene or alkylene group or R6, Y and the nitrogen atom together form a piperidine ring with or without an alkyl group as substituent therein, R7, R8 and R9 designate a hydroxy group or a hydroxy group etherified with methanol, ethanol or other aliphatic alcohol containing 1-6 carbon atoms mixed with an inert pharmaceutical carrier.  They may be administered orally in the form of a tablet when mixed with conventional fillers or parenterally in the form of a solution of the non-toxic addition salts.