反应详情

温度

120 °C

A mixture of 2-(3-chloro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (254c, 85 mg, 0.272 mmol), 1,1,1-trifluoro-2-methylpropan-2-amine hydrochloride (178 mg, 1.087 mmol, Oakwood Products, West Columbia, S.C.), Pd(tBu3P)2 (Strem, Newburyport, Mass.; 13.89 mg, 0.027 mmol), and K2PO4 (346 mg, 1.631 mmol) in DMA (2718 μl) was stirred at 120° C. for 5 h; the reaction was then heated to 145° C. for 2.5 d. The mixture was diluted with DCM (100 ml), and washed with saturated aq. NaHCO3 (2×75 ml) before the organic layer was separated, dried over Na2SO4, and concentrated. Purification by silica gel (100% DCM to 5% 2 M NH3 in MeOH/DCM) then by rpHPLC (Phenomenex Gemini C18, 10 μm, 150×30 mm; 10-100% ACN/water with 0.1% TFA) provided 2-(2-methyl-3-((1,1,1-trifluoro-2-methylpropan-2-yl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (254, 2% yield) as a yellow solid. MS (ESI, pos. ion) m/z: 404.1 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 1.81 (s, 6H) 2.63 (s, 3H) 2.97 (t, J=6.94 Hz, 2H) 3.66 (td, J=6.85, 2.54 Hz, 2H) 4.77 (s, 1H) 5.29 (br. s., 1H) 7.10 (d, J=2.15 Hz, 1H) 7.46 (t, J=7.92 Hz, 1H) 7.70 (dd, J=8.12, 1.27 Hz, 1H) 7.95 (dd, J=7.63, 1.37 Hz, 1H) 11.79 (br. s., 1H). 19F NMR (376 MHz, DMSO-d6) δ ppm −78.37 (3F, s).

1. temperaturethe reaction was then heated to 145° C. for 2.5 d
2. washwashed with saturated aq. NaHCO3 (2×75 ml) before the organic layer
3. customwas separated
4. dry with materialdried over Na2SO4
5. concentrationconcentrated
6. customPurification by silica gel (100% DCM to 5% 2 M NH3 in MeOH/DCM)