反应详情

温度

130 °C

To a solution of 1-chloro-8-methoxyisoquinoline-3-carbonitrile (230 mg, 1.05 mmol) in NMP (5 mL) was added (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate (294 mg, 1.57 mmol) and Et3N (212 mg, 2.1 mmol). The reaction mixture was heated to 130° C. for 45 minutes in a microwave reactor and was subsequently quenched with H2O (20 mL). The aqueous phase was extracted with EtOAc (3×10 mL). The organic layers were combined and concentrated in vacuo. The crude product was purified by column chromatography eluting with ethyl acetate and petroleum ether (EtOAc/PE=1:20-1:2 gradient) to give the title compound (380 mg, 2 batches, 52%). 1H NMR (400 MHz, CDCl3) δ ppm 7.85 (s, 1H), 7.55 (t, 1H, J=8.0 Hz), 7.25 (s, 1H), 6.97 (d, 1H, J=8.0 Hz), 4.60-4.80 (m, 1H), 4.01 (s, 3H), 3.78-3.79 (m, 1H), 3.27-3.57 (m, 3H), 2.29-2.34 (m, 1H), 1.94-1.99 (m, 1H), 1.48 (s, 9H).

1. customwas subsequently quenched with H2O (20 mL)
2. extractionThe aqueous phase was extracted with EtOAc (3×10 mL)
3. concentrationconcentrated in vacuo
4. customThe crude product was purified by column chromatography
5. washeluting with ethyl acetate and petroleum ether (EtOAc/PE=1:20-1:2 gradient)