反应详情

温度

130 °C

To a solution of 2-[4,6-dichloro-2-(morpholin-4-yl)pyrimidin-5-yl]ethanol (Preparation 1)(3.47 g, 12.5 mmol) and tert-butyl 3-amino-3-methylpyrrolidine-1-carboxylate (racemic from a commercial source or Preparation 3 for a chirally pure enantiomer) (5.00 g, 24.97 mmol) in NMP (40 mL) was added DIPEA (8.07 g, 62.44 mmol) at 10° C. The resulting mixture was stirred at 130° C. for 30 h. The mixture was diluted with EtOAc (30 mL) and washed with brine (20 mL×3). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue, which was purified by silica gel chromatography, eluting with petroleum ether/EtOAc (1:1) to give the title compound (4.40 g, 80%) as a light yellow gum. 1H NMR (400 MHz, 80° C., DMSO-d6) δ 6.48 (s, 1 H), 4.76 (t, J=5.0 Hz, 1 H), 3.76 (d, J=11.1 Hz, 1 H), 3.68-3.53 (m, 10 H), 3.45-3.28 (m, 3 H), 2.69 (t, J=6.24 Hz, 2 H), 2.35-2.26 (m, 1 H), 2.01-1.92 (m, 1 H), 1.49 (s, 3 H), 1.40 (s, 9 H). m/z (APCI+) for C20H32ClN5O4 442.2 (M+H)+.

1. washwashed with brine (20 mL×3)
2. dry with materialThe organic layer was dried over anhydrous Na2SO4
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. customto give a residue, which
6. customwas purified by silica gel chromatography
7. washeluting with petroleum ether/EtOAc (1:1)