GB817688A - Improvements in dialkylxanthine compounds - Google Patents

Abstract

Salt-like products of the general formula <FORM:0817688/IV (b)/1> (wherein R, R1 and R2 are alkyl groups of 1 to 4 carbon atoms, R3, R4, R5 and R6 are hydrogen atoms, alkyl groups of 1 to 3 carbon atoms or phenyl radicals and X is a dialkylxanthine or an 8-substituted dialkylxanthine radical in which the alkyl groups contain 1 or 2 carbon atoms are prepared by reacting the appropriate dialkylxanthine with a mixture of a tertiary amine NRR1R2 and an epoxy compound of formula <FORM:0817688/IV (b)/2> The reaction, which may be conducted at room temperature or at a raised temperature, is preferably carried out in an inert organic solvent, e.g. a lower aliphatic alcohol, dioxan or a glycol, both the amine and the epoxy compound advantageously being used in slight stoichiometric excess. Water may be present or, preferably, absent during the reaction and slight traces of water may be removed azeotropically by distilling off the organic solvents, when the product separates on cooling. In examples: (1) and (2) choline theophyllinate is prepared by heating theophylline with aqueous trimethylamine and ethylene oxide; (3), (7) and (9) the process of (1) is conducted anhydrously in isopropanol; (4) chloline 8-bromotheophyllinate is prepared as in (1); (5) choline 8-chlorotheophyllinate is similarly prepared; (6) choline 8-nitrotheophyllinate is prepared by the method of (3); (8) trimethylamine, 1 : 2-propyleneoxide and theophylline give theophylline (2 - hydroxypropyl) - trimethylamine by the method of (3). The use of triethylamine, tripropylamine, tributylamine, methyl - diethylamine, ethyl - dimethylamine, propyl - dimethylamine, butyl - dimethylamine, 1 : 2 - butylene oxide, 2 : 3 - butylene oxide, styrene oxide and diethylxanthines in the process of the invention is also referred to.