Ethyl Acetate → HCID 178432141, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 126; 85.0 mg, 0.287 mmol), cis-3-aminocyclobutanol hydrochloride (46.2 mg, 0.374 mmol), and DIPEA (0.150 mL, 0.861 mmol) in DMSO (2.0 mL) was stirred under argon at 100° C. for 30 min. The reaction mixture was subsequently cooled to 23° C. and diluted with water (10 mL). The resulting mixture was extracted with 5% MeOH/DCM (2×30 mL), and the combined extracts were sequentially washed with water (2×10 mL) and then concentrated onto silica gel. Chromatographic purification (silica gel, 50-100% EtOAc/Hexanes, then 100% EtOAc, then 0-10% MeOH/DCM) provided 2-(3-((cis-3-hydroxycyclobutyl)amino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (9.3 mg, 0.026 mmol, 11% yield) as a yellow solid. The combined aqueous layers from the aqueous workup were filtered through a fine glass frit, and the collected solid was sequentially washed with water (40 mL) and ether (30 mL), then dried in vacuo to provide additional 2-(3-((cis-3-hydroxycyclobutyl)amino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (92.2 mg, 0.254 mmol, 88% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.35 (1H, br. s.), 7.90 (1H, d, J=8.0 Hz), 7.56 (1H, d, J=7.6 Hz), 7.27-7.40 (2H, m), 7.09 (1H, br. s.), 6.95 (1H, br. s.), 5.18 (1H, d, J=6.3 Hz), 3.92-4.08 (1H, m), 3.41-3.50 (3H, m), 2.86-2.96 (2H, m), 2.74-2.86 (2H, m), 2.55 (3H, br. s.), 1.93-2.07 (2H, m). m/z (ESI, +ve) 364.0 (M+H)+.

Provenance & Evidence