Diisopropylethylamine → 8-bromo-7-fluoro-3-methyl-N-(1-methylcyclopropyl)quinoxalin-2-amine

Participants

Reaction Conditions

Reaction Steps

To a 15-mL glass reaction vial was added 5-bromo-3-chloro-6-fluoro-2-methylquinoxaline (600) (2.02 g, 7.33 mmol), 1-methylcyclopropanamine hydrochloride (ChemBridge, San Diego, Calif.) (1.420 g, 13.20 mmol) and DIEA (5.10 mL, 29.3 mmol) in DMSO (6 mL). The reaction mixture was stirred at 100° C. for 5 h. The reaction mixture was cooled to RT and poured over ice water. The precipitated orange solid was filtered, washed with water (2×5 mL), ether (2×5 mL). The orange solid was dried overnight to afford 1.77 g of 8-bromo-7-fluoro-3-methyl-N-(1-methylcyclopropyl)quinoxalin-2-amine (610a). The filtrate was extracted with EtOAc (2×10 mL). The organic extracts were washed with water and dried over Na2SO4, and concentrated in vacuo to give the crude material as an orange solid. The crude material was absorbed onto a plug of silica gel and purified by chromatography (with a gradient of 0-20% EtOAc in hexanes) to provide 8-bromo-7-fluoro-3-methyl-N-(1-methylcyclopropyl)quinoxalin-2-amine (610a) (474 mg) as an orange solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.74 (1H, dd, J=9.1, 5.8 Hz), 7.17 (1H, t, J=8.7 Hz), 5.29 (1H, br. s.), 2.49 (3H, s), 1.61 (3H, s), 0.86 (3H, d, J=4.7 Hz). 19F NMR (376 MHz, CDCl3) δ ppm −103.55 (1F, s). m/z (ESI, +ve ion) 310.0/312.0 (M+H)+.

Provenance & Evidence