Patent GB-1133406-A (GB)
Title: Substituted 1-amino phthalazines
Inventor: PARSONS DAVID GORDON
IPC: C07D237/34
Filed: 1967-06-26
Abstract: 1,133,406. Phthalazine derivatives. VANTOREX Ltd. 26 June, 1967, No. 29383/67. Addition to 1,094,044. Heading C2C. Novel compounds of the general formula and quaternary ammonium and acid addition salts thereof, wherein R is a lower alkoxy-lower alkyl group, a phenoxy group, a hydroxy-lower alkoxy group, a lower alkoxy-lower alkoxy group, a di-lower alkyl amino-lower alkyl group, a cyclic saturated organic base-lower alkyl group, a cyclic saturated organic base-lower alkoxy group, a cyclic saturated organic base group, or a di-lower alkyl amino group; wherein R 1  is hydrogen, a lower alkyl group, a phenyl group or a phenyl-lower alkyl group; wherein R 2  is hydrogen, a lower alkyl group or an alkanoyl group; wherein the benzenoid portion of the phthalazine nucleus and/or the phenyl group(s) of the R and/or R 1  substituents when present may be unsubstituted or substituted with one or more halogen atoms or lower alkyl, lower alkoxy, nitro, amino, di-lower alkyl amino, or carboxy groups; and wherein the cyclic saturated organic base when present may be substituted with one or more lower alkyl groups, are prepared by one of the following methods, (a) a hydroxy amine of the formula R 1 -NH-OR 2  is reacted with the compound of the general formula wherein X is a halogen atom, (b) a suitably substituted 1-aminophthalazine wherein R 2  is hydrogen is reacted with a lower alkyl carboxylic anhydride to produce a compound above wherein R 2  is an alkanoyl group, (c) the compounds falling within the general formula wherein the group-OR 3  is a phenoxy group, a hydroxy-lower alkoxy group, a lower alkoxylower alkoxy group, or a cyclic saturated organic base-lower alkoxy group said group being linked to the phthalazine nucleus by the oxygen atom, O; wherein R 1  is hydrogen, a lower alkyl group, a phenyl group or a phenyllower alkyl group; wherein R 2  is hydrogen, a lower alkyl group or an alkanoyl group; wherein the benzenoid portion of the phthalazine nucleus and/or the phenyl group(s) of the R and/or R 1  substituents when present may be unsubstituted or substituted with one or more halogen atoms or lower alkyl, lower alkoxy, nitro, amino, di-lower alkyl amino, or carboxy groups; and wherein the cyclic saturated organic base group when present may be substituted with one or more lower alkyl groups, which process comprises reacting a compound of the formula R 1 -NH-OR 2  with a compound of the formula which may be prepared by reacting a 1,4-dihalophthalazine with a sodium alcoholate or sodium phenolate of formula Na-OR 3 , (d) those compounds falling within the general formula wherein the group R 4  is a cyclic saturated organic base group linked to the phthalazine nucleus by the nitrogen atom, or a di-lower alkyl amino group; wherein R 1  is hydrogen, a lower alkyl group, a phenyl group or a phenyl-lower alkyl group; wherein R 2  is hydrogen, a lower alkyl group or an alkanyl group; wherein the benzenoid portion of the phthalazine nucleus and/or the phenyl group of the R 1  substituent when present may be unsubstituted or substituted but with one or more halogen atoms or lower alkyl, lower alkoxy, nitro, amino, di-lower alkyl amino, or carboxy groups; and wherein the cyclic saturated organic base group may be substituted with one or more lower alkyl groups, are prepared by reacting a substituted hydroxylamine of the formula R 1 -NH-OR 2  with a compound of the formula which may optionally be prepared by reacting a 1,4-diphenoxy-phthalazine with a di-lower alkyl amine or a saturated organic base. The di-phenoxy compound may be prepared by reacting the corresponding di-halo compound with a sodium alcoholate or sodium phenate. Method (c) above is also used to prepare compounds falling within the scope of Patent No. 1,094,044 and having the formula wherein the group -OR 3  is a lower alkoxy group or a di-lower alkyl amino-lower alkoxy group linked to the phthalazine nucleus by the oxygen atom, O, wherein R 1  is hydrogen, a lower alkyl group, a phenyl group or a phenyllower alkyl group; wherein R 2  is hydrogen, a lower alkyl group or an alkanoyl group; and wherein the benzenoid portion of the phthalazine nucleus and/or the phenyl group(s) of the R and/or R 1  substituents when present may be unsubstituted or substituted with one or more halogen atoms or lower alkyl, lower alkoxy nitro, amino, di-lower alkyl-amino. The term lower used above indicates groups containing up to 6 carbon atoms. Pharmaceutical compositions in conventional forms for oral, rectal or parenteral administration and having use as antipyretic, antiinflammatory, hypotensive, bronchodilator, and respiratory stimulant agents comprise an above novel compound and a diluent or carrier therefor. A method of treatment of animals excluding man which comprises administering the above novel compounds is also claimed.