Patent GB-1038725-A (GB)
Title: Substituted indanes and indenes
IPC: C07C63/34
Filed: 1963-06-05
Abstract: The invention comprises compounds of the general formula <FORM:1038725/C2/1> in which R1 is an aryl or heteroaryl (including such radicals having one or more substituents); R2 is a hydrogen or halogen atom or an alkyl, aralkyl, aryl, heteroaryl, hydroxy, alkoxy, haloalkyl, nitro, amino, dialkylamino, alkylthio, or arylthio radical; R3 is a hydrogen or a fluorine atom or a C1- 5 alkyl, C1- 5 haloalkyl, amino, acylamino, N-morpholino, dialkylamino, alkenyl, aralkylthio, hydroxy, or alkoxy radical, or together with R31 forms a methylene or a cyclopropyl radical; R31 is a hydrogen atom or, together with R31, forms a methylene or cyclopropyl group; each of R4, R5 and R6 is a hydrogen or halogen atom or an alkyl, alkoxy, nitro, amino, acylamino, alkylamino, dialkylamino, dialkylaminoalkyl, sulphamoyl, alkylthio, mercapto, alkylsulphonyl, arylsuiphonyl, cyano, carboxyl, carbalkoxy, carbamido, aryl, halogenoalkyl, alkenoxy, aralkoxy, alkenyl, aryloxy, cycloalkyl or cylcoalkoxy; and M is hydroxy, C1- 5 alkoxy, phenoxy, substituted C1- 5-alkoxy, amino, alkylamno, dialkyl-1 amino, N - morpholino, piperidino, piperazino, substituted piperazino, pyrrolidino, hydroxyalkylamino, carboxymethylamino, polyhydroxyalkylamino, dialkylaminoalkylamino, or aminoalkylamino radical or the group OM*, in which M* is a cation; with the proviso that when R2, R4, R5 and R6 are all hydrogen atoms, R1 is a substituted aryl or heteroaryl radical; and the 2,3-dihydro derivatives of the said compounds; and the preparation of compounds wherein M is alkoxy, substituted alkoxy or phenoxy by reacting a compound of the general formula <FORM:1038725/C2/2> wherein R* is C1- 5 alkyl, substituted G5 alkyl or phenyl, with a compound R1CHO in an inert solvent in the presence of a strong base, and optionally saponifying the ester to form a salt or the free acid, and further converting the acid into its acid chloride and forming an amide; or reacting an appropriate inden- or indan-1-one with a triphenyl-R1-phosphinyl compound of the formula R1-CH = P(Ph)3.  The following intermediates and starting materials are prepared: ethyl 5-methoxy-2-methyl - 3 - indenylacetate; ethyl 2 - hydroxy - 2 p - methoxyphenyl) - 1 - methylpropionate; 6-methoxy - 2 - methylindanone; ethyl (1 - hydroxy - 2 - methyl - 6 - methoxy - indanyl) acetate; ethyl - 5 - dimethylamino - 3 - hydroxy - 2-methyl - 3 - indanyl acetate, ethyl 3 - hydroxy-2 - methyl - 5 - nitro - 3 - indanylacetate; ethyl 5-nitro - 2 - methyl - 3 - indenylacetate; 5 - methoxy - 1 - oxo - 3 - indanylacetic acid and its methyl ester; a  - (5 - methoxy - 2 - methyl - 3-indenyl) propionic acid and its ethyl ester; ethyl a  - (5 - methoxy - 2 - methyl - 3 - indenyl) propionate; ethyl 4 - fluoro -, 2 - fluoro -, 3-fluoro - and 4 - trifluoro - a  - methyl cinnamates and their free acids and the corresponding hydro-cinammic acids, 2 - methyl - 6 - fluoro-, - 4-fluoro -, - 5 - fluoro and - 6 - trifluoroindan - 1-ones; ethyl 2 - methyl 5 - fluoro -, 7 - fluoro -, -6-fluoro - and - 5 - trifluoromethyl - 3 - indenyl-acetates; 2 - methoxy - 4 - methyl - indan - 1-one; ethyl (1 - hydroxy - 2 - methoxy - 7 - methylindanyl) acetate; ethyl 2 - methoxy - 7 - methyl-3 - indenyl acetate; ethyl 2,6 - dimethyl - 3-indenylglyoxalate, ethyl 2,6 - dimethyl - 3-indenyl - a  - aminoacetate; ethyl 2,6 - dimethyl-3 - indenyl - a - dimethylaminoacetate; 2-methyl - 5 - methoxy indene; 2 - methyl - 6-methoxy - 1 - indanol; methyl 2 - methyl - 5-methoxy - 3 - indenyl glyoxalate; ethyl 2-methyl - 5 - methoxy - 3 - indenyl - a  - dimethylamino acetate; methyl 5 - methoxy - 2 - methyl-3 - indenyl a - hydroxy acetate; methyl 5-methoxy - 2 - methyl - 3 - indenyl - a  - tosyloxy-acetate; methyl 5 - methoxy - 2 - methyl - 3 - indenyl - a - methoxyacetate; methyl 5 - methoxy-2 - methyl - 3 - indenyl - a  - fluoroacetate methyl 5 - methoxy - 2 - methyl - 3 - indenyl - a  - morpholinoacetate; methyl 5 - methoxy - 2 - methyl 3 - indenyl - a  - fluoromethylacetate; 6 - methoxy - 2 - fluoro - methylindanones; ethyl 2 - fluoro-methyl 5 - methoxy - 3 - indenylacetate; ethyl a -(2,6 - dimethyl - 3 - indenyl) acrylate; ethyl 2,6-dimethyl - 3 - indenyl - a  -acetamido - acetate; a  - methyl - b  - (p - methylthiophenyl) propionic acid; 1 - p - chlorobenzylidene - 2 - methyl - 5-methoxy - 3 - indenyl acetonitrile and its a -allylacetonitrile.  Pharmaceutical compositions comprise the compounds of the invention together with an inert pharmaceutical carrier diluent or coating. The compositions may be in the form of a tablet, powder, capsule, granule, solution, suspension, ointment, lotion, cream or sterile injectable solution.  The compounds are anti-inflammatory and anti-pyretic agents.