Patent GB-1369736-A (GB)
Title: Azaindene derivatives
IPC: C07D221/04
Filed: 1972-09-14
Abstract: 1369736 4-, 5-, 6- or 7-Azaindenes and -azaindanes MERCK & CO Inc 14 Sept 1972 [20 Sept 1971] 42738/72 Heading C2C Novel compounds (I): and 2,3-dihydro derivatives thereof, in which (a), (b), (c), and (d) are each selected from C and N, only one of said (a), (b), (c), and (d) being N at any one time; (Ar) is aryl; R 1  is alkylsulphinyl or alkylsulphonyl; R<SP>1</SP> 1  is hydrogen, halogen, hydroxy, alkoxy, haloalkyl, alkylthio, alkylsulphinyl, alkylsulphonyl, haloalkyleneoxy, haloalkylenethio, haloalkylenesulphinyl, cyano, mercapto, or sulphonamido; R 2  is hydrogen, alkyl, aralkyl, aryl, heteroaryl, halogen, hydroxy, alkoxy, haloalkyl, alkylthio, NO 2 , NH 2 , dialkylamino or arylthio; R 3  is hydrogen, C 1-6  alkyl, halogeno C 1-6  alkyl, fluorine, amino, acylamino, dialkylamino, N-morpholino, alkenyl, aralkylthio, hydroxy or alkoxy; R<SP>1</SP> 3  is hydrogen or, together with R 3 , forms methylene or ethylene; R 4 , R 5  and R 6  each are hydrogen, alkyl, alkoxy, nitro, amino, acylamino, alkylamino, dialkylamino, dialkylaminoalkyl, sulphamyl, alkylthio, mercapto, alkylsulphinyl, alkylsulphonyl, halogen, cyano, carboxyl, carbalkoxy, carbamido, aryl, halogenoalkyl, alkenyloxy, aralkyloxy, alkenyl, aryloxy, cycloalkyl and cycloalkyloxy; and M is hydroxy, C 1-6  alkoxy, substituted C 1-6  alkoxy, phenoxy, #-acetamidoethoxy, trityloxy, #-N-piperidinylethoxy, # - N - pyrrolidinylethoxy, N - pyrrolidinylmethoxy, 1-methyl- or -ethyl-pyrrolidin-2-yl methoxy, # - (4 - methyl - piperazin - 1 - yl) ethoxy, #-morpholinoethoxy, amino, alkylamino, dialkylamino, N - morpholino, hydroxyalkylamino, aminoalkylamino, benzylamino and the group OMe in which Me is a cation, are made by standard methods, especially using an aromatic aldehyde in order to introduce the arylidene group. The following compounds are also prepared: the thioethers corresponding to (I) (i.e. R 1  is alkylthio-), 2 - carbethoxy - 5 - chloro - 2 - methyl- 4 - aza - 1 - indanone, 5 - hydroxy - and - chloro- 2 - methyl - 4 - aza - 1 - indanones, methyl 5- chloro - 4 - aza - 1 - hydroxy - 2 - methyl - indanyl- 1-acetate, methyl 6-chloro-2-methyl-7-aza-3-(indene- and -indanylidene)-acetates, ethyl 2-(2<SP>1</SP>,2<SP>1</SP>- dicarbethoxy)-ethyl-nicotinate and -6-methylthio nicotinate, 2 - carbethoxy - 5 - methylthio - 4 - aza- 1 - indanone, 2 - methyl - 2 - carbethoxy - 5- methylthio - 4 - aza - 1 - indanone, 7 - aza - 1- indanone, 2 - methyl - 7 - aza - 1 - indanone, 2- methyl - 5 - methylthio - 4 - aza - 1 - indanone, 1- p - methylsulphinylbenzylidene - 2 - methyl - 6- chloro - 7 - azaindene - 3 - acetyl chloride, 1 - pmethylsulphinylbenzylidene - 2 - methyl - 6 - chloro- 7 - azaindene - 3 - acetonitrile and - 3 - α - allylacetonitrile, methyl 2 - methyl - 7 - aza - 1 - hydroxyindane - 3 - acetate, methyl 2 - methyl - 7- aza - 3 - (indene - and - indanylidene) - acetates, ethyl 5-bromo- and -fluoro-6-chloro-2-methylnicotinates, ethyl 5-bromo- and -fluoro-2-methylnicotinates, ethyl 5-bromo- and -fluoro-2-(2<SP>1</SP>,2<SP>1</SP>- dicarbethoxy) - ethyl - nicotinates, 6 - bromo - and -fluoro - 2 - carbethoxy - 4 - aza - 1 - indanones, 6- bromo- and -fluoro-2-carbethoxy-2-methyl-4-aza- 1-indanones, 6-bromo- and -fluoro-2-methyl-4- aza-1-indanones, methyl 6-bromo- and -fluoro-1- hydroxy - 2 - methyl - 4 - azaindanyl - 3 - acetates, methyl 5-bromo- and -fluoro-2-methyl-7-azaindenyl - 1 - acetates, ethyl 5 -fluoro - 6 - chloro- 2 - methylnicotinate, ethyl 5 -fluoro - 2 - bromomethylnicotinate and ethyl 5-bromo-6-hydroxy-2- methylnicotinate. Pharmaceutical preparations showing antiinflammatory, analgesic and anti-pyretic actions contain (I) as active ingredient. Administration may be orally, topically, rectally or parenterally.