反应详情

温度

160 °C

To a suspension of 1-chloro-8-fluoroisoquinoline-3-carbonitrile (0.8 g, 3.88 mmol) and Et3N (0.78 g, 7.76 mmol) in NMP (5 mL) was added (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate (0.87 g, 4.66 mmol) at RT. The resulting mixture was heated at 160° C. for 30 minutes in a microwave reactor. The reaction was quenched with water and the mixture was extracted with EtOAc (3×30 mL). The organic phase was dried over Na2SO4 and concentrated in vacuo. The crude product was purified by column chromatography eluting with ethyl acetate and petroleum ether (EtOAc/PE=1:50-1:9 gradient) on silica gel to give the title compound (1.12 g, 81%). 1H NMR (400 MHz, CDCl3) δ ppm 7.56-7.52 (m, 1H), 7.44-7.42 (d, 1H, J=8.0 Hz), 7.29 (s, 1H), 7.21-7.18 (m, 1H), 6.47-6.43 (m, 1H), 4.73 (br s, 1H), 3.77-3.72 (dd, J1=6.4 Hz, J2=11.6 Hz, 1H), 3.48-3.19 (m, 3H), 2.26 (br s, 1H), 1.90 (br s, 1H), 1.41 (s, 9H); ESI-MS m/z [M+H-tert-butyl]+ 301.2.

1. customThe reaction was quenched with water
2. extractionthe mixture was extracted with EtOAc (3×30 mL)
3. dry with materialThe organic phase was dried over Na2SO4
4. concentrationconcentrated in vacuo
5. customThe crude product was purified by column chromatography
6. washeluting with ethyl acetate and petroleum ether (EtOAc/PE=1:50-1:9 gradient) on silica gel