GB1380765A - Phthalimidine derivatives - Google Patents

Abstract

1380765 Isoindole derivatives; organolithium compounds SANDOZ Ltd 14 March 1972 [19 March 1971] 11831/72 Headings C2C and C2J Novel compounds of formula in which R 1 signifies hydrogen, alkoxy of 1 to 4 carbon atoms, fluorine, chlorine or trifluoromethyl; R 2 signifies hydrogen, alkyl or alkoxy of 1 to 4 carbon atoms, fluorine, chlorine, trifluoromethyl, nitro or amino; R 3 signifies hydrogen, alkyl or alkoxy of 1 to 4 carbon atoms, fluorine, chlorine, trifluoromethyl, nitro, amino, dialkylamino in which each alkyl is independently of 1 to 4 carbon atoms, or phenyl; R 4 signifies hydrogen, alkyl or alkoxy of 1 to 4 carbon atoms, or trifluoromethyl; or R 1 and R 2 , R 2 and R 3 , or R 3 and R 4 together signify methylenedioxy; R 5 signifies hydrogen, alkyl of 1 to 4 carbon atoms, phenyl, allyl, benzyl, 2- hydroxyethyl, N-methylcarbamoyloxyethyl or carbethoxymethyl; Q signifies in which R 6 and R 7 each independently signifies methyl or ethyl or together form a -CH 2 - chain of 4 to 6 carbon atoms and R 8 signifies methyl, vinyl or allyl, or Q is -C(CH 3 )=R 9 , in which R 9 signifies alkylidene of 1 to 4 carbon atoms; and Z signifies hydroxy, amino, alkoxy of 1 to 4 carbon atoms, or dialkylaminoethylamino in which each alkyl is independently of 1 to 4 carbon atoms; with the provisos that (i) no more than two of R 1 to R 4 are other than hydrogen, (ii) when one of R 1 and R 3 is halogen, the other is not halogen, (iii) only one of R 1 and R 3 , or R 2 and R 4 may be alkoxy, (iv) no two trifluoromethyl groups are on adjacent carbon atoms, (v) only one of R 2 and R 3 may be nitro or amino, (vi) when R 1 to R 5 are H and Z is OH then Q is not tert.-butyl, are prepared by one of the following methods: (a) a compound of Formula II: is treated with an inorganic acid halide and then a compound of formula R 5 NH 2 ; (b) a compound of Formula III: wherein R<SP>1</SP> 5 is C 1-4 alkyl or phenyl is reacted with a compound of formula QCOX where X is Cl or Br followed by hydrolysis; (c) a compound of Formula IV: wherein R<SP>1</SP> 1 and R<SP>1</SP> 4 are H, C 1-4 alkoxy or CF 3 , and R<SP>1</SP> 2 and R<SP>1</SP> 3 are H, C 1-4 alkyl, C 1-4 alkoxy, F or Cl, is reacted with tert.-butyl magnesium halide; (d) nitration to introduce a nitro group in the benzene ring; (e) treating a compound of Formula I wherein Z is OH with a compound of formula HZ<SP>1</SP> where Z<SP>1</SP> is amino, alkoxy or dialkylaminoethylamino; or (f) a compound of Formula III above is reacted with a compound of formula QCN and then hydrolysed to give the compounds of Formula I wherein Z is NH 2 . Intermediates of Formula II above are prepared by treating a compound of Formula Ia1 wherein R<SP>1</SP> 5 is methyl or phenyl, with a strong base. Intermediates of Formula III (shown above) are prepared by action of Li butyl on the benzamide. Pharmaceutical compositions in conventional forms and having tranquillizing sedative or hypnotic activity comprise an above novel compound and a carrier or diluent.