US 3,947,466 A · Intermediates and process for the production of certain triazolobenzodiazepines

Abstract

A multi-step process for the preparation of 1-[(amino - or substituted amino)methyl]-6-phenyl-4H-s-triazolo-[4,3-a][1,4]benzodiazepines of the formula VI: ##SPC1## wherein R' is hydrogen or alkyl of 1 to 3 carbon atoms, inclusive, and wherein the rings A and B are unsubstituted or substituted by one or two substituents selected from the group consisting of chloro, fluoro, bromo, nitro, and trifluoromethyl, which comprises: treating a compound of the formula I: ##SPC2## wherein rings A and B are defined as above, with acetic anhydride and formic acid to obtain compound II: ##SPC3## wherein A and B rings have the significance as above, treating compound II with sufficient formaldehyde to produce compound III, the 3,5-bis(hydroxymethyl)derivative of II; treating III with phthalimide, triphenylphosphine and diethyl azodicarboxylate to give compound IV, the 3,5-bis(phthalimidomethyl) derivative of II; and treating IV with hydrazine hydrate to obtain a compound of formula V ##SPC4## wherein rings A and B are defined, as herein above. Compound V can then be alkylated in known manner to give those compounds of formula VIa which corresponds to formula VI when R' is desired to be alkyl. The compounds of formula VI have antidepressant and antianxiety effects in mammals and birds.

Claims17

Dependent claims

A process for the production of a compound of the formula V:

##SPC12##
wherein the rings A and B are unsubstituted or substituted by chloro, fluoro, bromo, nitro or trifluoromethyl, which comprises:
1. reacting a compound of formula I ##SPC13##
wherein a and B are defined as above, with an equimolar mixture of formic acid and acetic anhydride at 0.degree. to 25.degree.C and then warming the mixture at 90.degree.-118.degree. to obtain the corresponding compound of formula II:
##SPC14##
wherein rings A and B are defined as above;
2. heating in an inert organic solvent a compound of formula II with paraformaldehyde to between 118.degree. and 150.degree.C., to obtain the corresponding compound III:
##SPC15##
wherein rings A and B are defined as above;
3. treating compound III, dissolved in an inert organic solvent, with phthalimide, triphenylphosphine and diethyl azodicarboxylate at a temperature between 0.degree. and 35.degree.C., to obtain the corresponding compound IV:
##SPC16##
wherein rings A and B are defined as above;
4. treating the compound of formula IV with hydrazine hydrate at 60.degree. to 100.degree.C in an alkanol of 1 to 3 carbon atoms, inclusive, to obtain the compound of formula V as defined above.

10 more elements

Dependencies are inferred from the claim text.

Intermediates and process for the production of certain triazolobenzodiazepines

Life of this patent

Intermediates and process for the production of certain triazolobenzodiazepines

Life of this patent

Abstract

Claims17