Patent GB-1068698-A (GB)
Title: Aminoketones and cyclic compounds derived therefrom
IPC: C07D213/53
Filed: 1965-08-18
Abstract: Novel aminoketones of the general formula <FORM:1068698/C2/1> (wherein Ar represents a heterocyclic aromatic ring which may be substituted by one or more C1- 4 alkyl groups and/or be fused to a further aromatic ring, R1 represents a hydrogen atom or an alkoxycarbonyl, cyano, acyl, alkyl or aryl group, R2 represents a hydrogen atom or an alkyl, hydroxyalkyl, cycloalkyl, aryl, aralkyl, acyl, halo-substituted acyl, alkarylsulphonyl or tetrahydroazepinyl group and R3 represents a hydrogen atom or an alkyl or aralkyl group, or R2 and R3 together represent the residue of a dicarboxylic acid or, together with N, form a saturated heterocyclic ring which may contain a second hetero-atom and/or be substituted by a C1- 4 alkyl group, and M represents a bivalent group including or consisting of a bivalent, saturated, alicyclic or straight or branched acyclic, aliphatic hydrocarbon radical and, if desired, also including a bivalent aromatic radical and/or a hetero-atom, and containing a total of at least 5 and not more than 19 carbon (and, where present, hetero-atoms), or (when R3 is H and R2 is not an acyl group) their anhydro-derivatives of the general formulae <FORM:1068698/C2/2> <FORM:1068698/C2/3> and acid addition salts of such of these compounds as contain a basic group, are prepared by reacting an organometallic compound of the formula Ar-CHR1-Q(IV) (wherein Q represents an alkali metal atom or the radical -MgHal of a Grignard compound, Hal being Cl or Br) with a reactive derivative of an aminocarboxylic acid of the formula HOOC.M.NR2R3 (V) or with a cyclic compound of the formula <FORM:1068698/C2/4> <FORM:1068698/C2/5> (in the latter of which A represents a halogen atom or an alkoxy or alkylthio group), in an anhydrous solvent, with subsequent hydrolysis where necessary, or by reacting a compound of the formula Ar-CHR1-Y (wherein Y represents an acyl, alkoxycarbonyl or cyano group) with one of the aforesaid carboxylic acid derivatives or cyclic compounds, in the presence of a basic condensation agent, or (for compounds in which R1 is an alkyl, aryl, alkoxycarbonyl or acyl group) by reacting an organometallic compound having one of the formulae <FORM:1068698/C2/6> <FORM:1068698/C2/7> <FORM:1068698/C2/8> (wherein Q1 represents an alkali metal atom) with a compound R1Hal (wherein Hal represents a halogen atom) or R1OAlk (wherein Alk represents Me or Et), or (for compounds in which R1 is an acyl group) by reacting a corresponding compound in which R1 is H with a ketene, or (for compounds in which either or each of R2 and R3 is an alkyl, hydroxyalkyl, cycloalkyl, aralkyl or acyl group) by reacting a corresponding compound in which either or each of R2 and R3 is H with the appropriate alkyl, hydroxyalkyl, cycloalkyl or aralkyl halide or arylsulphonate, carboxylic acid halide or anhydride or ketene, or (for aminoketones in which R1 is H) by hydrolysing and decarboxylating a corresponding compound in which R1 is an alkoxycarbonyl or cyano group, or (for aminoketones in which R2 is H) saponifying a corresponding compound in which R2 is an acyl group, and in all cases, if desired and possible, converting the product into an acid addition salt.  Alternative methods are also outlined. The aminoketones are, in appropriate cases, converted into their anhydro-derivatives by the action of alkalis, whilst the reverse charge is brought about by aqueous acids.  Lactim O-alkyl ethers (VII, A = alkoxy) are prepared by treating the corresponding lactams with alkylating agents.  Pharmaceutical compositions, e.g. tablets, coated tablets, capsules, lozenges, ampoules or suppositories, having hypotensive, local anaesthetic and antipyretic activity, comprise compounds (I), (II) or (III), or non-toxic acid addition salts of such of them as contain a basic group, together with a pharmaceutical carrier or excipient.