GB760039A - Isoindole derivatives - Google Patents

Abstract

The invention comprises compounds of the formula: <FORM:0760039/IV(b)/1> in which R is the parent nucleus of an anhydride of a vicinal cis-cyclic dicarboxylic acid selected from the group consisting of phthalic, tetrahydrophthalic, endomethylene - tetrahydrophthalic, 3 - methyleneoxyhexahydrophthalic, 5 - methyl - tetrahydrophthalic, 3,5 - dimethyltetrahydrophthalic, endoxyhexahydrophthalic, hexahydrophthalic, and tetrachlorophthalic anhydride and cantharidin, R1 is an alkyl radical having from 1 to 6 carbon atoms or is part of a heterocyclic ring system such as morpholino, pyrrolidino and piperidino rings, n is a whole number from 2 to 6 and X is an anion selected from the group consisting of chlorine, bromine, iodine and methyl sulphate. Such compounds are obtained by reacting a dialkylaminoalkylamine with a molecular equivalent of the appropriate vicinal cis-cyclic dicarboxylic acid anhydride to give the corresponding N - dialkylamino - imide which is reduced with lithium aluminium hydride or sodium in alcohol or catalytically or electrolytically to the corresponding isoindole derivative, and the latter is then quaternated. In Example (1) N-diethylaminoethyl hexahydrophthalimide (obtained by reacting hexahydrophthalic anhydride with diethylaminoethylamine) is reduced with lithium aluminium hydride to N - diethylaminoethyl - octahydroisoindole, reaction of which with methyl iodide gives the corresponding di-methiodide. By a generally similar series of reactions there are prepared (2) N-diethylaminoethyl 4,7,8,9-tetrahydroisoindoline dimethyl quaternary iodide; (3) N - diethylaminoethyl - 1,3 - dihydroisoindole dimethiodide; (4) diethylaminoethyl 4,7,8,9 - tetrahydro - 4,7 - endomethanoisoindoline dimethiodide; (5) diethylaminoethyl hexahydro - 4,7 - endoxy - isoindoline dimethiodide; (6) N-dimethylaminoethyl tetrachloroisoindoline dimethiodide; (7) dimethylaminoethyl - 4 - methylpentahydro - 4,7 - endoxyisoindoline dimethiodide; (8) N-dimethylaminoethyl - 6 - methyl - 4,7,8,9 - tetrahydroisoindoline dimethiodide; (9) N-dimethylaminoethyl - 4,6 - dimethyl 4,7,8,9 - tetrahydroisoindoline dimethiodide; (10) N-dimethylaminoethyl - 8,9 - dimethyl 4,7 - endoxytetrahydroisoindoline dimethiodide. Table I lists N - dialkylaminoalkyl - D 4 - tetrahydrophthalimides, 3,6 - endomethylene - D 4 - tetrahydrophthalimides, 3,6 - endoxyphthalimides, phthalimides and hexahydrophthalimides in which the dialkylamino group is selected from dimethylaminoethyl, diethylaminoethyl, dimethylaminopropyl, diethylaminopropyl, morpholinoethyl and morpholinopropyl groups. Table II lists N-dialkylaminoalkyl-4,7,8,9-tetrahydroisoindolines, 4,7,8,9 - tetrahydro - 4,7-endomethanoisoindolines, isoindolines, 4,7,7-endoxyoctahydroisoindoles and octahydroisoindoles having similar dialkylaminoalkyl groups to those present in the compounds of Table I, and also includes the corresponding dimethiodides.