121898-98-4Relevant articles and documents
Mannich Reactions of Heterocycles with Dimethyl(methylene) Ammonium Chloride: A High Yield, One-step Conversion of Estazolam to Adinazolam
Gall, Martin,Kamdar, Bharat V.,Lipton, Michael F.,Chidester, Connie G.,DuChamp, David J.
, p. 1649 - 1661 (2007/10/02)
The readily prepared ammonium salt, (CH3)2N=CH2(1+)*Cl(1-), 4, functionalized heterocycles differently, but in a predictable fashion, under neutral, basic or acidic conditions.Triazolo- and imidazobenzophenones 1b' and 5, which primarily underwent intramolecular isomerization to indolols 2a' and 6a rather than intermolecular electrophilic substitution under conditions of the normal aqueous Mannich reaction, were converted with 4 to the desired benzophenone derivatives, 1c' and 7, respectively, in moderate yields.The 1-unsubstituted triazolo- or imidazobenzodiazepines, 10a estazolam and 10b, were transformed to the corresponding 1-(dimethylamino)methyl derivatives, 11a (adinazolam) and 11b, in good to moderate yields (61percent and 32percent, respectively.) Under acidic reaction conditions, 1-methyl triazolobenzodiazepine, 10d (alprazolam), afforded 12e, the product of attack at C-4 of the triazolobenzodiazepine ring system.Under strongly basic conditions in which the anion of 10d was generated prior to reaction with 4, both 12e and its isomer, 15, were formed.These results complement the report that 4 may be used to functionalize the 1-methyl position of triazolobenzodiazepines, and further demonstrate the versatility of reagent 4 in heterocyclic synthesis.
