GB1211731A - Quinazoline derivatives - Google Patents

Abstract

1,211,731. Quinazolones. SANDOZ Ltd. 23 Oct., 1967 [21 Nov., 1966; 11 May, 1967], No. 48090/67. Addition to 1,195,066. Heading C2C. The invention comprises compounds of the formula in which R signifies a hydrogen or halogen atom other than an iodine atom, R 1 signifies a hydrogen atom, an alkyl radical of 1 to 5 carbon atoms, an allyl or a propargyl radical and R 2 signifies the radical in which Y signifies a hydrogen atom or an alkyl radical of 1 to 4 carbon atoms, they are prepared by reacting a compound of Formula II in which R and R 2 are as defined above, with urea, to yield a compound of Formula I wherein R 1 = H. Compounds wherein R 1 is not hydrogen are prepared by reacting the alkali metal derivative of the compound of Formula I, with R<SP>1</SP> 1 X where R<SP>1</SP> signifies an alkyl radical of 1 to 5 carbon atoms, or an allyl or propargyl radical and X signifies a bromine, chlorine or iodine atom. Compounds of Formula I, wherein R 1 = methyl are prepared by oxidizing a compound cf Formula V or its halide VI. Compounds of the general Formula I may be prepared by reacting a compound of Formula VII wherein R, R 1 and R 2 are as defined above with the proviso that R 1 must not signify a tertiary alkyl radical of which the tertiary carbon atom is directly attached to the nitrogen atom, with a lower alkyl (C 1 -C 8 ) carbamate in the presence of a catalytic amount of a Lewis acid at a temperature of at least 140‹ C. Compounds of Formula V are prepared by the reduction of compounds of Formula VI, which are prepared by the methylation of the corresponding quinazolines, which are prepared by the oxidation of the corresponding 3,4-dihydroquinazolines, which are obtained from quinazoline and thiophene. Compounds of Formula VII are prepared from the corresponding 2-[o-(N-methyl-N-tosylamino) benzoyl] thiophene, which is obtained from the corresponding o-(N-methyl-N-tosylamino) benzoyl chloride and thiophene. Pharmaceutical compositions containing as active ingredients compounds of the general Formula I in admixture with a pharmaceutically acceptable carrier are administered orally or parenterally and have anti - inflammatory activity.