| 摘要 |
1308198 4-(2-Thienyl)-2(IH)-quinazolinones SANDOZ Ltd 29 April 1970 [9 May 1969] 20589/70 Addition to 1211731 Heading C2C Novel 4-(2 - thienyl) - 2(IH) - quinazolinones of the general formula wherein R is a hydrogen, chlorine, fluorine or bromine atom or a C 1-5 alkyl or C 1-5 alkoxy group, n is 1 or 2, R 1 is a hydrogen atom or a C 1-5 alkyl, allyl or propargyl group and R 2 is a Y-substituted 2-thienyl group, in which Y is a hydrogen, fluorine, chlorine or bromine atom or a C 1-4 alkyl group, provided that when Y is a hydrogen atom or a C 1-4 alkyl group, then (i) when n is 1, R is other than a hydrogen or halogen atom and (ii) when n is 2, each R is other than a hydrogen atom, are prepared (a) when R 1 is other than a tertiary alkyl group in which the tertiary carbon atom is directly attached to the ring nitrogen atom, by reaction of a 2-(2-amino-benzoyl)-thiophene of the general formula wherein R<SP>1</SP> 1 is as the desired meaning of R 1 , with a C 1-5 alkyl carbamate in the presence of a catalytic amount of a Lewis acid and at a temperature of at least 140‹ C; (b) when R 1 is a hydrogen atom or C 1-5 alkyl group, by oxidation of a 4-(2-thienyl)-3,4-dihydro-2(1H)-quinazolinone of the general formula wherein R<SP>11</SP> 1 is as the desired meaning of R 1 ; and (c) by cyclization of an α-(2-thienyl)-2- amino-benzylideneamine of the general formula with phosgene. Novel 4 - (2 - thienyl) - 3,4 - dihydro - 2(1H)- quinazolinones of the third general formula above are prepared by reaction of a phenylurea of the general formula with a thiophene-2-carboxaldehyde of the general formula R 2 CHO at an elevated temperature and under substantially anhydrous conditions. 2 - (2 - Isopropylamino - 4 - methyl - benzoyl)- thiophene is prepared by reaction of 2-tosylamino-4-methyl-benzoyl chloride with thiophene in the presence of aluminium chloride, treatment of the resulting 2-[2-(N-tosylamino)-4-methylbenzoyl]-thiophene with concentrated sulphuric acid and reaction of the resulting 2-(2-amino- 4-methyl - benzoyl) - thiophene with 2- iodopropane in the presence of sodium carbonate. α - (2 - Thienyl) - 2 - isopropylamino - 4 - methylbenzylideneamine is prepared by reaction of 2 - (2 - isopropylamino - 4 - methylbenzoyl)- thiophene with ammonia in the presence of zinc chloride. Pharmaceutical compositions comprise, as active ingredient either (i) a 4-(2-thienyl)-2(1H)- quinazolinone of the first general formula above or (ii) a 4-(2-thienyl)-3,4-dihydro-2(1H)-quinazolinone of the third general formula above, in association with a pharmaceutically acceptable carrier. The active ingredients have antiinflammatory activity and active ingredients (i) also have antipyretic and analgesic activity. |
