Patent GB-1214408-A (GB)
Title: 3,5-diamino-6-halo-pyrazinamide derivatives
Inventor: CRAGOE EDWARD JETHRO JR
IPC: C07D241/26
Filed: 1968-09-03
Abstract: 1,214,408. 3,5 - Diamino - 6 - halo - pyrazinamide derivatives. MERCK & CO. Inc. 3 Sept., 1968 [7 Sept., 1967; 21 March, 1968], No. 41777/68. Heading C2C. [Also in Division A5] 3,5 - Diamino - 6 - halo - pyrazinamide derivatives of the general formula wherein R<SP>1</SP> is a hydrogen atom or a C 1-5  alkyl, C 3-5  alkenyl, C 3-5  alkynyl, C 3-6  cycloalkyl, C 3-6  cycloalkyl-C 1-3  alkyl, di(C 1-3  alkyl)amino-methyl-C 1-3  alkyl, (hydroxy-C 1-5  alkyl)methyl, (polyhydroxy - C 1-5  alkyl) - methyl, #, #, # - trifluoro-C 1-3  alkyl, phenyl-C 1-3  alkyl, halophenyl- C 1-3  alkyl, heterocyclic-C 1-3  alkyl in which the heterocyclic moiety is a 5- or 6-membered ring containing oxygen or nitrogen or both, phenyl, halophenyl, C 1-3  alkyl-phenyl, C 1-3  alkoxy, phenyl-C 1-3  alkoxy or amino group; and R<SP>2</SP> is a hydrogen atom or a C 1-5  alkyl group; or R<SP>1</SP> and R<SP>2</SP> are alkylene groups linked together directly or through a hetero atom to form a heterocyclic structure with the nitrogen atom to which they are attached; Y is a chlorine, bromine or iodine atom; and R<SP>6</SP> is a C 1-5  alkyl, C 1-3  alkoxymethyl-C 1-5  alkyl, cyano.C 1-5  alkyl, (C 1-3  alkoxy)carbonyl-C 1-5  alkyl, phenyl-C 1-5  alkyl, di-(C 1-3  alkyl)aminomethyl-C 1-5  alkyl, 2 - (2 - imidazolinyl) - amino - methyl - C 1-5  alkyl, 1-pyrrolidinyl-C 1-5  alkyl, piperidino-C 1-5  alkyl, hexahydro-1-azepinyl-C 1-5  alkyl, morpholino-C 1-5  alkyl, 4-(C 1-3  alkyl)-1 -piperazinyl-C 1-5  alkyl, pyridyl-C 1-5  alkyl, faryl-C 1-5  alkyl, tetrahydropyranyl-C 1-5  alkyl, C 3-5  alkenyl, C 3-5  alkynyl, phenyl, halophenyl, C 1-3  alkyl-phenyl, C 1-3  alkoxy-phenyl, cyano, amino, di(C 1-3  alkyl)- amino, N-C 1-3  alkyl-N-(phenyl - C 1-3  alkyl)- amino, di[phenyl- (C 1-3  alkyl)]amino, pyridylamino, pyrimidinylamino, quinolinylamino, pyrrolidino, piperidino, hexahydro-1-azepinyl, morpholino or 4-(3,5-diamino- 1,2,4-triazolyl) group; a group of the formula in which R<SP>7</SP> is a C 1-5  alkyl, phenyl, halophenyl, C 1-3  alkyl-phenyl or C 1-3  alkoxy-phenyl group; a group of the formula in which R<SP>8</SP> is a hydrogen atom or a phenyl or C 1-5  alkyl group, R<SP>9</SP> is a hydrogen atom or a C 1-5  alkyl, hydroxy-C 1-5  alkyl, phenyl-C 1-5  alkyl, halophenyl-C 1-5  alkyl, (C 1-3  alkyl)-phenyl- C 1-5  alkyl, (C 1-3  alkoxy)-phenyl-C 1-5  alkyl, naphthyl-C 1-5  alkyl, balonaphthyl-C 1-5  alkyl, (C 1-3  alkyl) - naphthyl - C 1-5  alkyl, (C 1-3  alkoxy) - naphthyl - C 1-5  alkyl, pyridyl - C 1-5  alkyl, morpholino-C 1-5  alkyl, furyl-C 1-5  alkyl, 1 - pyrrolidyl - C 1-5  alkyl, C 1-3  alkoxy-C 1-5  alkyl, C 3-5  alkenyl, C 2-5  alkylideneamino, (phenyl - C 2-5  alkylidene)amino, hydroxy, phenyl, C 1-3  alkyl-phenyl, C 1-3  alkoxy-phenyl, halophenyl, C 1-3  alkoxy or phenyl-C 1-3  alkoxy group and R<SP>10</SP> is a hydrogenation or a C 1-5  alkyl group, or R<SP>9</SP> and R<SP>10</SP> are alkylene groups linked together to form, with the nitrogen atom to which they are attached, a heterocyclic ring containing from 5 to 8 atoms, optionally including a further heteroatom, or R<SP>8</SP> and R<SP>9</SP> are alkylene groups linked together to form, with the nitrogen atom to which they are attached, a heterocyclic ring containing from 5 to 7 ring atoms; a group of the formula in which R<SP>11</SP> is an hydrogen atom or a C 1-5  alkyl group, R<SP>12</SP> is a hydrogen atom or a C 1-5  alkyl, hydroxy-C 1-5  alkyl, phenyl-C 1-5  alkyl, halophenyl-C 1-5  alkyl, (C 1-3  alkyl)-phenyl-C 1-5  alkyl, phenyl, halophenyl, C 1-3  alkyl-phenyl, C 1-3  alkoxy-phenyl or amino group and R<SP>13</SP> is a hydrogen atom, or R<SP>11</SP> and R<SP>13</SP> are alkylene groups linked together to form a diazacyclic ring containing from 5 to 7 ring atoms with the nitrogen atoms to which they are attached; are prepared by reaction of a 3,5-diamino-6-halopyrazinoyloxyacrylamide of the general formula wherein R<SP>3</SP> is a methyl, ethyl, n-propyl, isopropyl, phenyl, (C 1-3  alkyl)-phenyl or sulphophenyl group, in which case an internal salt is formed with an amino group; and R<SP>4</SP> is a hydrogen atom; or R<SP>3</SP> and R<SP>4</SP> are linked to form an o-phenylene group with the carbon atom to which R<SP>3</SP> and R<SP>4</SP> are attached; R<SP>5</SP> is a C 1-5  alkyl group; with an amine of the general formula R<SP>6</SP>NH 2 . Certain of the 3,5-diamino-6- halo-pyrazinamide derivatives of the first general formula above are novel.