Benzylamine → N-benzyl-6-bromobenzo[c][1,2,5]oxadiazol-4-amine

Participants

Reaction Conditions

Reaction Steps

4,6-dibromobenzo[c][1,2,5]oxadiazole 4 (0.9678 g, 3.48 mmol) and benzylamine (1.9 mL, 17.4 mmol) were dissolved in DMSO (10.5 mL) under argon and stirred in a sealed tube for 3 days, after which time, the tube was heated to 60° C. for 12 hours. Upon cooling to room temperature, the reaction was diluted with water and extracted with EtOAc. The combined organic layers were washed with H2O (5×), 1 N HCl (aq), saturated NaHCO3 (aq) and brine before drying with Na2SO4, filtering and concentrating. The dark solid was recrystallized from EtOH and the dark crystals were collected by filtration and dried to afford 0.4516 g (43% yield) of N-benzyl-6-bromobenzo[c][1,2,5]oxadiazol-4-amine. This material (0.1980 g, 0.651 mmol), benzoylpiperazine hydrochloride (0.1771 g, 0.781 mmol) and Cs2CO3 (0.6353 g, 1.95 mmol) were added to a tube. The tube was evacuated and purged with argon (3×). Toluene (2 mL) and NMP (1.2 mL) were then added to the tube and its contents were degassed for 15 minutes, at which point Pd2(dba)3 (0.0119 g, 0.0130 mmol) and BINAP (0.0162 g, 0.026 mmol) were quickly added, the tube was sealed and heated at 100° C. overnight. Upon cooling to room temperature, the reaction was diluted with water and extracted with EtOAc. The combined organic layers were washed with H2O (5×), 1 N HCl(aq), saturated NaHCO3 (aq) and brine before drying with Na2SO4, filtering and concentrating. The crude material was purified via chromatography (40% EtOAc/Hexanes) to give 0.188 g (70% yield) of TRV-1256. 1H NMR (500 MHz, CDCl3) δ=7.46-7.43 (m, 5H), 7.39-7.36 (m, 4H), 7.34-7.31 (m, 1H), 6.13 (d, J=1.0 Hz, 1H), 5.88 (s, 1H), 5.32 (t, J=5.5 Hz, 1H), 4.48 (d, J=5.5 Hz, 2H), 3.90 (br s, 2H), 3.58 (br s, 2H), 3.29 (br s, 2H), 3.15 (br s, 2H).

Provenance & Evidence