GB988001A - Improvements in or relating to lysergic acid derivatives - Google Patents

Abstract

The invention comprises compounds of the formula <FORM:0988001/C2/1> (wherein R1 is C1- 4 alkyl, C7- 10 monocyclic aralkyl or C2- 4 alkenyl and <FORM:0988001/C2/2> and their acid-addition salts; and their preparation (1) by hydrolysing a corresponding amide (wherein the nitrogen atom may be substituted by C1- 4 alkyl or hydroxyalkyl radicals or wherein the substituted amino portion of the amide radical is the tripeptide radical of a natural water insoluble ergot alkaloid) with an alkali metal hydroxide; or (2) by treating a corresponding N-unsubstituted compound, i.e. a lysergic or dihydrolysergic acid, with an alkali metal amide in liquid ammonia and reacting the resulting alkali metal salt with the appropriate halide R1-Hal. In process (1), when 9,10-dehydro-compounds are saponified the product is a mixture of lysergic and isolysergic acid derivatives and these are separated by dissolving in a suitable acid and precipitating with a base, by dissolving in a base and fractionally precipitating with an acid or by means of a combination of the two operations, or by fractional recrystallization, or by absorption analysis. In process (2), pure 1-methyl-D-lysergic acid may be isolated by bringing an aqueous solution to pH 4.5 to 5 with acetic acid, or by evaporating the solution to dryness, and pouring methanol over the residue to dissolve small quantities of 1-methyl-isolysergic acid and inorganic salts.