Patent GB-1285711-A (GB)
Title: New benzoxazine derivatives
Inventor: PESSON MARCEL
IPC: C07C205/37
Filed: 1968-11-08
Abstract: 1285711 2 - Carbamoyl - 3 - oxo - 2,3 - dihydro - 1,4 - benzoxazines LABORATOIRE ROGER BELLON 10 Nov 1969 [8 Nov 1968] 53168/68 Heading C2C Novel 2 - carbamoyl - 3 - oxo - 2,3 - dihydro- 1,4-benzoxazines of the general formula wherein R 1  and R 2  are each a hydrogen atom or a C 1-6  alkyl, cycloalkyl or optionally substituted aryl group, or R 1  and R 2 , together with the nitrogen atom to which they are attached form a heterocyclic radical wherein the heterocyclic ring contains 5 or 6 ring members, which ring may include a hetero atom in addition to the nitrogen atom; R 3  is a hydrogen atom or a C 1-6  alkyl or -CH 2 CONR 6 R 7  group, in which R 6  and R 7  are each a hydrogen atom or C 1-6  alkyl group or NR 6 R 7  is a morpholino or piperidino group; and R 4  and R 5  are each a hydrogen or halogen atom or a C 1-6  alkyl or C 1-6  alkoxy group, are prepared (i) when R 3  is a hydrogen atom, by (a) condensing an alkali metal salt of an o-nitrophenol of the general formula wherein M is an alkali metal, with a C 1-6  alkyl halomalonate of the general formula XCH(COOR<SP>11</SP>) 2 , wherein X is a halogen atom and R 2  is a C 1-6  alkyl group, (b) reductively cyclizing the resulting alkyl o-nitrophenoxymalonate of the general formula and (c) reacting the resulting 2-carbalkoxy-3- oxo - 2,3 - dihydro - 1,4 - benzorazine of the general formula with ammonia or an amine of the general formula R 1 R 2 NH; (ii) when R 3  is a hydrogen atom and R 1  and R 2  are not hydrogen atoms, by (a) condensing an alkali metal salt of an o-nitrophenol of the second general formula above with a halomalondiamide of the general formula CXH(CONR 1 R 2 ) 2 , (b) reducing the resulting oitnrophenoxymalondiamide of the general formula and (c) cyclizing the resulting o-aminophenoxymalondiamide of the general formula by heating in an acid medium; (iii) when R 3  is a hydrogen atom and R 1  and R 2  are not hydrogen atoms, by (a) condensing an alkali metal salt of an o-nitrophenol of the second general formula above with a halomalonic ester-amide of the general formula XCH(COOC 2 H 5 ) (CONR 1 R 2  ) and (b) reductively cyclizing the resulting 0-nitrophenoxymalonic ester-amide of the general formula and (iv) when R 3  is other than a hydrogen atom, by reaction of an alkali metal salt of the corresponding 2 - carbamoyl - 3 - oxo - 2,3 - dihydro- 1,4-benzoxazine of the first general formula above wherein R 3  is a hydrogen atom with a compound of the general formula R 3 X, wherein R 3  is other than a hydrogen atom. Bromomalondiamides of the seventh general formula above (X is a bromine atom) are prepared by reaction of a malondiamide of the general formula CH 2 (CONR 1 R 2 ) 2  with bromine in carbon tetrachloride. Bromomalonic esteramides of the tenth general formula above (X is a bromine atom) are prepared analogously. Pharmaceutical compositions having analgesic, anticonvulsant and hypnotic activity comprise, as active ingredient, a 2-carbamoyl-3- oxo-2,3-dihydro- 1 4-benzoxazine of the first general formula above, in association with a pharmaceutical carrier.