Mannich reactions of heterocycles with dimethyl(methylene) ammonium chloride: A high yield, one‐step conversion of estazolam to adinazolam

摘要: The readily prepared ammonium salt, (CH3)2N+ = CH2Cl−, 4, functionalized heterocycles differently, but in a predictable fashion, under neutral, basic or acidic conditions. Triazolo- and imidazobenzophenones 1b′ 5, which primarily underwent intramolecular isomerization to indolols 2a′ 6a rather than intermolecular electrophilic substitution conditions of the normal aqueous Mannich reaction, were converted with 4 desired benzophenone derivatives, 1c′ 7, respectively, moderate yields. 1-unsubstituted triazolo- imidazobenzodiazepines, 10a (estazolam) 10b, transformed corresponding 1-(dimethylamino)methyl 11a (adinazolam) 11b, good yields (61% 32%, respectively.) Under reaction conditions, 1-methyl triazolobenzodiazepine, 10d (alprazolam), afforded 12e, product attack at C-4 triazolo[4,3-a][1,4]benzodiazepine ring system. strongly anion was generated prior both 12e its isomer, 15, formed. These results complement report that may be used functionalize position triazolobenzodiazepines, further demonstrate versatility reagent heterocyclic synthesis.