Patent GB-898322-A (GB)
Title: Indenes substituted by heterocycles and process for their manufacture
Filed: 1960-12-07
Abstract: The invention comprises 2-pyridyl-indenes of the general formula <FORM:0898322/IV (b)/1> their N-oxides and physiologically tolerable acid addition salts, in which R represents a hydrogen or a halogen atom or an unsubstituted alkyl or a halogen-alkyl or alkoxyalkyl group, an alkoxy or alkylmercapto group, or a nitro or a free amino, alkylamino, dialkylamino or acylamino group, R1 represents an alkyl group, R2 represents a hydrogen atom or an alkyl group and Py represents an unsubstituted or alkyl-substituted pyridyl group and the preparation thereof, wherein either a 2-pyridyl-indanol of the formula <FORM:0898322/IV (b)/2> in which one of R3 and R4 represents an hydroxyl group and the other a hydrogen atom, is dehydrated, or a 1-phenyl-2-pyridyl-propane-1 : 2-diol of the formula <FORM:0898322/IV (b)/3> or a salt thereof is reacted with a strong Lewis acid, in either case the resulting indene is isolated, and, if desired, a substituent is introduced into the aromatic ring of the resulting indene and/or any substituent present is converted and/or any resulting salt is converted into a free compound or a resulting free compound is converted into a salt, an N-oxide or a salt of an N-oxide thereof.  The group R may be a trifluoromethyl group and the acyl residue in the acylamino substituent may be derived from an alkane-, alkene-, hydroxyalkane-, alkoxyalkane-, alkanoylalkane-, halogen-alkane carboxylic acid; alkane-, alkene-, hydroxyalkane-, alkoxyalkane-, alkoxyalkene-, halogen-alkane dicarboxylic acids and semi-esters thereof; alkane-, alkene-, hydroxyalkane - tricarboxylic acids; cycloaliphatic carboxylic and dicarboxylic acids; cycloaliphatic-aliphatic carboxylic acids; mono- or bi-cyclic arylcarboxylic acids or aryl-aliphatic carboxylic acids, including benzoic, dihydrocinnamic, cinnamic, mandelic, salicyclic, 4-aminosalicyclic 2-phenoxy benzoic, 2-acetoxy benzoic and trimethoxy benzoic acid; mono- or bicyclic aryldicarboxylic acids; or mono- or bicyclic unsaturated heterocyclic carboxylic acid.  The group R may be introduced into the aromatic ring by, for example, nitration and the resultant nitro group may be produced to the free amino group or in the presence of an alkanal to form an alkylamino group.  Free amino groups may also be alkylated or acylated in manner known per Se or replaced by a halogen atom through the diazonium salt.  N-oxides are prepared by oxidation with a per-acid.  2-Pyridyl-indanols (where R3 is the hydroxyl group) are prepared from the corresponding 2-pyridyl-indanones by a Grignard reaction with an R1-magnesium halide and (where R4 is a hydroxyl group and R2 a hydrogen atom) by reduction of the corresponding 2-pyridyl-indanones. 2-Pyridyl-indanones are prepared by the following sequence of reactions <FORM:0898322/IV (b)/4> 1 - Phenyl - 2 - pyridyl - propane - 1 : 2 - diols (particularly 2-phenyl- and 2-(p-chlorophenyl)3-pyridyl-(3)-butane-2,3-diols) are prepared by reducing a mixture of a ketone of the formula <FORM:0898322/IV (b)/5> and a pyridyl methyl ketone of formula R2CH2COPy by electrolytic reduction (see Group XXXVI) or by U.V. irradiation in the presence of a hydrogen donor, e.g. a secondary alcohol.  Pharmaceutical compositions for oral or parenteral administration comprise the 2-pyridyl indenes and as pharmaceutically acceptable carrier.  The composition have a suprarenal cortex inhibiting effect.