Patent GB-953606-A (GB)
Title: Benz-cycloalkan-1-ones and process for their manufacture
IPC: C07D213/55
Filed: 1961-12-07
Abstract: The invention comprises compounds of the formula: <FORM:0953606/C2/1> in which Ph is a 1,2-phenylene radical which may bear halogen, alkyl, haloalkyl, hydroxyl, etherified hydroxyl, nitro, amino or N-acylamino substituents, Py is a pyridyl, e.g. a 3- or 4-pyridyl, radical, R is hydrogen or alkyl and (CnH2n), in which n is an integer from 2 to 7, is an alkylene group separating the 1,2-phenylene radical and the carbon atom carrying the pyridyl group by two or three carbon atoms, and oximes, hydrazones, semicarbazones, thiosemicarbazones and salts and quaternary ammonium derivatives of these compounds. The compounds are prepared by reacting a phenylalkyl carboxylic acid containing a pyridyl group in the a -position, or a functional derivative thereof, e.g. a compound of the formula H.Ph.(CnH2n).C(Py)(R).Ro wherein Ro is a carboxyl group or a functionally converted carboxyl group, or a salt thereof, with a strong Lewis acid ring closing agent, followed, if desired, by conversion into a salt or free base, alkylation of any product wherein R is hydrogen, introduction or conversion of substituents in the phenylene ring Ph and/or conversion into an oxime, hydrazone, semicarbazone or thiosemicarbazone or quaternary derivative.  When Ro is a functionally converted carboxylic group, it may suitably be a cyano, carbamyl, carbalkoxy or carbonyl halide group. The compounds of the invention may also be prepared by reacting a salt of a benz [b] cyclo-alkanone of the formula: <FORM:0953606/C2/2> with a pyridyl halide.  The products may be resolved into their optically active isomers by means of optically active acids such as tartaric, malic, mandelic, camphorsulphonic, quinic or di-o-toluyl-tartaric, if desired.  a -Pyridyl-phenylalkanoic acids and functional derivatives thereof, of the formula: H.Ph.(CnH2n) C(Py)(R).Ro, are made by reacting a salt of a functional derivative of pyridylacetic acid of the formula Py.CH(R).Ro1, wherein Ro1 is a functionally converted carboxylic group such as a cyano group, with a compound of the formula H.Ph(CnH2n)X, wherein X is a reactively esterified OH group e.g. a halogen atom, and if necessary converting the functionally converted carboxyl group in the product into a free carboxyl group or into another functionally converted group.  For example, 4-phenyl-2-(3-pyridyl)-butyric acid is made via the corresponding nitrile and amide; 5-phenyl-2-(3-pyridyl)-valeric acid is made via the nitrile and 4-(3-chlorophenyl)-2-(3-pyridyl)-butyric acid is made by reacting m-chlorophenyl magnesium bromide with ethylene oxide, converting the resulting 2-(3-chlorophenyl)-ethanol into the bromide by means of PBr3, reacting with 3-pyridyl-acetonitrile to give 4-(3-chlorophenyl)-2-(3-pyridyl)-butyronitrile and hydrolyzing. Pharmaceutical preparations for treatment of conditions causing adrenal cortical hyperfunction and for diagnosis of pituitary gland conditions, comprise the above compounds of the invention including their salts with inorganic or organic acids and quaternary derivatives in admixture with an organic or inorganic, solid or liquid carrier suitable for enteral or patenteral administration. The preparations may suitably take the form of capsules, tablets, dragees, solutions, suspensions or emulsions and may contain preserving, stabilizing, wetting and emulsifying agents, salts for varying the osmotic pressure and buffers.