反应详情

温度

90 °C

To a solution of racemic ethyl 3-amino-3-(1-methylcyclopentyl)propanoate, 33a, (0.40 g, 2.01 mmol) and 2,6-dichloro-5-fluoro-pyridine-3-carbonitrile (0.46 g, 2.41 mmol) in THF (20 mL) was added triethylamine (0.67 mL, 4.82 mmol). The reaction mixture was stirred at 90° C. in a pressure tube for 18 hours. The reaction mixture was filtered and the resulting filtrate was concentrated in vacuo. The product was purified by silica gel chromatography (25% EtOAc/Hexanes) to afford 380 mg of the desired product as a racemic mixture: 1H NMR (400 MHz, CDCl3) δ 7.31 (d, J=9.7 Hz, 1H), 5.56 (d, J=8.9 Hz, 1H), 4.68 (td, J=9.6, 3.6 Hz, 1H), 4.07 (q, J=7.1 Hz, 2H), 2.68 (dd, J=14.8, 3.7 Hz, 1H), 2.46 (dd, J=14.8, 9.3 Hz, 1H), 1.77-1.62 (m, 4H), 1.61-1.49 (m, 2H), 1.47-1.37 (m, 1H), 1.35-1.26 (m, 1H), 1.19 (t, J=7.1 Hz, 3H), 1.01 (s, 3H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=3.81 minutes (M+H) 354.98. The racemic mixture was submitted to SFC chiral separation to give the individual enantiomers, 143a and 143b. The (R)-enantiomer, 143a, was taken forward into the next synthetic step.

1. filtrationThe reaction mixture was filtered
2. concentrationthe resulting filtrate was concentrated in vacuo
3. customThe product was purified by silica gel chromatography (25% EtOAc/Hexanes)