5-Aryl-1,3-dihydro-2H-1,3,4-benzotriazepin-2-ones

Synthesis and CNS Activity of 3-Substituted 7-Chloro-5-Phenyl-1,3,4-Benzotriazepin-2-ones

“…IVa-3.4 (s, 2H, -NH2) and 9.02 ( s , lH, -NNHCO); IR and NMR spectra were identical with those of the compound prepared as described previously (7).…”

Chemoselective Alkylation for Diversity-Oriented Synthesis of 1,3,4-Benzotriazepin-2-ones and Pyrrolo[1,2][1,3,4]benzotriazepin-6-ones, Potential Turn Surrogates

“…1,4-Benzodiazepin-2-ones 1 are common targets because of their biological properties and medicinal applications, which may be due in part to their potential to mimic peptide γ-turn secondary structures (Figure ). − Although their aza counterparts have received relatively less attention, 1,3,4-benzotriazepin-2-ones 2 possess intriguing biological activity. For example, 5-cyclohexyl triazepinones 3 and 4 have, respectively, exhibited activity as a parathyroid hormone-1 receptor antagonist and an orally active cholecystokinin-2 (CCK 2 ) antagonist (Figure ).…”

“…Since original syntheses from 2-aminobenzophenone, 1,3,4-benzotriazepin-2-ones have been commonly prepared by cyclization of the corresponding hydrazone with a phosgene equivalent and by a one-pot annulation with a carbazate often at high temperature (e.g., 190 °C). Ring closure has also been achieved by palladium-catalyzed cyclization of aryl isocyanates and 2-haloaryl hydrazones under microwave irradiation as well as condensation of anthranilic acid hydrazide with isatins, which provided the corresponding spiro­[1,3,4-benzotriazepine-2,3′-indole]-2′,5­(1 H ,1′ H )-diones .…”

“…8 Although relatively little is known about 1,3,4-triazepin-2-one conformation, similar to the amino acid component in 1,4-diazepin-2-ones, 9 the aza-phenylglycine residue of 7-chloro-3,5-diphenyl-1,2-dihydro-3H-1,3,4-benzotriazepin-2-one 5 was observed by X-ray crystallography to adopt ϕand ψ-dihedral angle values close to those of the central residue of an ideal γ-turn. 10 Since original syntheses from 2-aminobenzophenone, 4 1,3,4benzotriazepin-2-ones have been commonly prepared by cyclization of the corresponding hydrazone with a phosgene equivalent and by a one-pot annulation with a carbazate often at high temperature (e.g., 190 °C). Ring closure has also been achieved by palladium-catalyzed cyclization of aryl isocyanates and 2-haloaryl hydrazones under microwave irradiation 11 as well as condensation of anthranilic acid hydrazide with isatins, which provided the corresponding spiro[1,3,4-benzotriazepine-2,3′indole]-2′,5(1H,1′H)-diones.…”

“…To demonstrate the potential to further diversify pyrrolo-[1,2][1, 3,4]benzotriazepin-6-one 7, analogous conditions were employed as described above for the alkylation of triazepinone 6. The aniline nitrogen of pyrrolobenzotriazepinone 7b was thus alkylated with potassium tert-butoxide and 1-bromo-4-chlorobutane in 84% yield (Scheme 3).…”