反应详情

温度

80 °C

Charge 450 mL (2.58 mol) of N-ethyl-N-isopropylpropan-2-amine into a 15° C. solution of tert-butyl 2-chloro-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxylate (220 g, 860.37 mmol) and 2,3-dihydro-1H-inden-2-amine (137.7 g, 1.03 mol) in 1-methylpyrrolidin-2-one (3.6 L). Heat the resulting mixture to 80° C. for 16 h, then cool to 30° C. and transfer the resulting mixture into 5 L of water at 25° C. Filter the resulting solid and rinse the filter cake with water (2×300 mL). Reslurry the solid in ethyl acetate (350 mL) for 45 min at 15° C. Filter the slurry, rinsing with 15° C. ethyl acetate (2×250 mL), and dry to give the title compound (226 g, 75%) as an off-white solid. 1H NMR (d6-DMSO) 1.45 (s, 9H), 2.87 (dd, J=7.2, 15.8 Hz, 2H), 3.24 (dd, J=7.2, 15.8 Hz, 2H), 4.36 (d, 10.4 Hz, 2H), 4.44 (d, J=12.8 Hz, 2H), 4.60 (m, 1H), 7.14 (m, 2H), 7.20 (m, 2H), 7.55 (d, J=6.8 Hz, 1H), 8.27 (d, J=7.2 Hz, 1H).

1. temperaturecool to 30° C.
2. customat 25° C
3. filtrationFilter the resulting solid
4. washrinse the filter cake with water (2×300 mL)
5. customfor 45 min
6. customat 15° C
7. filtrationFilter the slurry
8. washrinsing with 15° C. ethyl acetate (2×250 mL)
9. customdry