反应详情

温度

100 °C

Prepared similarly to that described in Example 131 using 2-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 126; 44 mg, 0.148 mmol), rac-tetrahydro-2H-pyran-3-amine hydrochloride (40.9 mg, 0.297 mmol, Matrix Scientific, Columbia, S.C.), and DIPEA (129 μl, 0.742 mmol), heating at 100° C. for 1 h. Purification by silica gel (100% DCM to 6% MeOH/DCM) provided rac-2-(2-methyl-3-((tetrahydro-2H-pyran-3-yl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (75% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.72-1.83 (m, 3H) 2.13-2.21 (m, 1H) 2.56 (s, 3H) 2.91 (t, J=6.85 Hz, 2H) 3.35-3.42 (m, 2H) 3.45 (td, J=6.85, 2.35 Hz, 2H) 3.87 (d, J=10.76 Hz, 1H) 4.01-4.08 (m, 1H) 4.12-4.20 (m, 1H) 6.86 (d, J=7.24 Hz, 1H) 6.94 (br. s., 1H) 7.08 (d, J=2.15 Hz, 1H) 7.35 (t, J=7.82 Hz, 1H) 7.59 (dd, J=8.12, 1.27 Hz, 1H) 7.91 (dd, J=7.53, 1.27 Hz, 1H) 12.07 (br. s., 1H). MS (ESI, pos. ion) m/z: 378.2 (M+1). Chiral purification [SFC: Chiralpak OH-J (30×150 mm), A: liquid CO2, B: 20 mM NH3 in MeOH/EtOH/isopropanol (1:1:1), isocratic: 70:30 (A:B), 70 mL/min] separately afforded 2-(2-methyl-3-((tetrahydro-2H-pyran-3-yl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (first eluting enantiomer, 208) and 2-(2-methyl-3-((tetrahydro-2H-pyran-3-yl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (second eluting enantiomer, 209).

1. customPrepared similarly to that
2. customPurification by silica gel (100% DCM to 6% MeOH/DCM)