Patent GB-1193035-A (GB)
Title: Substituted Imidazo Pyrazinones
Inventor: CRAGOE EDWARD JETHRO JR
IPC: C07D241/28
Filed: 1968-08-05
Abstract: 1,193,035. Imidazo-pyrazinone derivatives. MERCK & CO. 5 Aug., 1968 [8 Aug., 1967; 9 May, 1968], No. 37296/68. Heading C2C. Novel compounds I in which R<SP>1</SP> and R<SP>2</SP> are H, C 2-6  alkanoyl, C 3-7  cycloalkyl, C 3-5  alkenyl, (C 1-3  alkoxy) carbonyl or a C 1-5  alkyl radical unsubstituted or substituted by one or more OH, C 1-3  alkoxy, a heterocyclic group having 5 or 6 ring atoms with 1 or more O and/or N heteroatoms, (C 1-3  alkoxy) carbonyl, hydrazinocarbonyl, phenyl, amino, C 1-5  alkylamino or di(C 1-5 -alkyl) amino; R 3  is H, C 3-5  alkenyl, C 3-5  alkynyl, C 3-7  cycloalkyl, phenyl, halogenated phenyl, (C 1-3  alkyl) phenyl, (C 1-3  alkoxy) phenyl, C 1-4  alkoxy, amidino or a C 1-6  alkyl radical unsubstituted or substituted by one or more OH, C 1-3  alkoxy, C 3-6  cycloalkyl, halo, a heterocyclic group as defined above, phenyl, halophenyl, (C 1-3  alkyl) phenyl, (C 1-3  alkoxy) phenyl, or -NR<SP>6</SP>R<SP>7</SP>; R<SP>4</SP> is H or an aliphatic hydrocarbon radical; or R<SP>3</SP> and R<SP>4</SP> together with the adjacent N form a heterocyclic ring which may also contain an O atom, an N 2  group or a bis[di(C 1-5 -alkyl) amino] methylene group; R<SP>6</SP> is H or C 1-5  alkyl; R<SP>7</SP> is H, or C 1-5  alkyl; or R<SP>6</SP> and R<SP>7</SP> together with the adjacent N form a heterocyclic group optionally containing an O atom; and R<SP>5</SP> is H, halo, C 1-6  alkyl, phenyl, halophenyl, (C 1-3  alkyl) phenyl or (C 1-3  alkoxy) phenyl are prepared (a) by diazotization of a compound II wherein R<SP>10</SP> is H, C 1-5  alkyl, C 3-7  cycloalkyl, C 1-5  hydroxyalkyl, (C 1-3  alkoxy)-C 1-5  alkyl, C 3-5  alkenyl, or di(C 1-5  alkyl) amino-C 1-5  alkyl, with an alkali metal nitrite in acid medium, followed by heating the resultant azide in alcoholic solution to give a compound I in which R<SP>1</SP> is R<SP>10</SP> and R<SP>2</SP> is H; (b) by reaction of a compound I in which R<SP>1</SP> and R<SP>2</SP> are H with a C 1-5  alkyl iodide or bromide, a di (C 1-5  alkyl) sulphate, a C 1-3  alkyl C 2-6 -α-bromoalkanoate, a C 1-3  alkyl chloroformate, a C 2-6  alkanoic acid anhydride, a C 3-7  cycloalkyl iodide or bromide, a di (C 1-5  alkyl) amine and formaldehyde or morpholine or piperidine and formaldehyde to give a compound I in which R<SP>1</SP> and R<SP>2</SP> are both the same and are C 1-5  alkyl, (C 1-3  alkoxy) carbonyl-(C 1-5  alkyl), (C 1-3  alkoxy) carbonyl, C 2-6  alkanoyl; C 3-7  cycloalkyl, di (C 1-5  alkyl) amino methyl, morpholinomethyl or piperidinomethyl; or (c) by reaction of a compound I in which R<SP>1</SP> is R<SP>10</SP> and R<SP>2</SP> is H with a reagent selected from those listed under (b) to give an appropriately substituted compound I. Compounds of Formula III in which R is alkyl are prepared by reaction of R 3 NH(R 4 ) with an appropriate 5,6-dichloro compound. Compounds of Formula IV are prepared by reaction of R<SP>1</SP>NH 2  with the appropriate 2-bromo compound which in turn is prepared from the 2-amino compound by reaction with sodium nitrite, bromine and hydrobromic acid. Compounds of Formula II are prepared by reaction of the appropriate compounds III and IV with hydrazine. Pharmaceutical compositions useful as antihypertensive agents comprise a compound I together with a suitable carrier or diluent and are administered orally, topically or parenterally. Compounds I also exhibit diuretic, saluretic, bronchodilator, gastric-acid-inhibiting and cardiac stimulating activity.