N-bromobutanimide → HCID 89783867, compound

Participants

Reaction Conditions

Reaction Steps

Argon was bubbled through a slurry of tributyl(1-ethoxyvinyl)stannane (0.335 ml, 0.992 mmol), Pd(PPh3)4 (0.076 g, 0.066 mmol), and 5-bromo-3-phenoxyquinoxalin-2-amine (0.209 g, 0.661 mmol) in 6 mL toluene for 2 min. The reaction was fitted with a water-cooled reflux condenser, flushed with argon, and heated to reflux. After 3 h, CuI (0.025 g, 0.132 mmol) was added. After 3 h, the reaction was cooled, concentrated in vacuo, and the material was treated with DCM and purified by silica gel chromatography using 0-100% EtOAc/hexane. The resulting yellow oil (0.134 g), containing a mixture of desired product and starting material was used without further purification. This material was dissolved in 5 mL THF and treated with water (0.126 ml, 6.98 mmol). The reaction was cooled to 0° C. and NBS (0.037 ml, 0.436 mmol) was added in one portion. After 20 min the reaction was checked and judged complete. The reaction was partitioned between saturated aq. NaHCO3 and DCM. The organic layer was separated, and the aq. layer was extracted 3×DCM. The combined organic layers were then dried over Na2SO4, filtered, and concentrated in vacuo. The resulting brown foam was treated with piperidine-2,4-dione (0.123 g, 1.090 mmol), NH4OAc (0.269 g, 3.49 mmol), and 3 mL EtOH, sealed, and placed in a 50° C. oil bath. After 4 h, the reaction was cooled and partitioned between saturated aq. NaHCO3 and DCM. The aq. layer was extracted with DCM (3×), and the combined organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. This material was dissolved in 2.5 mL DMSO, filtered, and purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 10-60% ACN/H2O with 0.1% TFA); product-containing fractions were treated with saturated aq. NaHCO3 and DCM. The organic layer was separated, and the aq. layer was extracted 3×DCM. The combined organic layers were then dried over Na2SO4, filtered, and concentrated in vacuo to give 2-(2-amino-3-phenoxyquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.019 g, 0.051 mmol, 11.73% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 10.72 (1H, br. s), 7.57-7.72 (3H, m), 7.26-7.51 (7H, m), 6.87-6.94 (1H, m), 6.83 (1H, dd, J=1.9, 0.5 Hz), 3.30-3.34 (2H, m), 2.37-2.46 (2H, m). m/z (ESI, +ve) 372.0 (M+H)+.

Provenance & Evidence