Reaction Steps
To a solution of 1′-(pyrrolidin-3-ylmethyl)-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one (0.24 g, 0.65 mmol) and triethylamine (0.15 mL, 1.1 mmol) in dichloromethane (5 mL) was added isopropyl isocyanate (0.10 mL, 1.0 mmol) and the solution was stirred at ambient temperature for 35 min. The reaction was diluted with saturated sodium bicarbonate (40 mL) and was extracted with dichloromethane (3×20 mL). The combined organic solution was dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by flash column chromatography with dichloromethane/diethyl ether (2/1) afforded N-(1-methylethyl)-3-[(2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)methyl]pyrrolidine-1-carboxamide (0.24 g, 81%) as a colorless solid: mp 107-115° C. (hexanes); 1H NMR (300 MHz, CDCl3) (diastereomers) δ7.31 (dd, J=7.6, 7.6 Hz, 0.5H), 7.30 (dd, J=7.7, 7.7 Hz, 0.5H), 7.18 (d, J=6.8 Hz, 1H), 7.07 (dd, J=7.5, 7.5 Hz, 1H), 6.90 (d, J=7.8 Hz, 1H), 6.45 (s, 1H), 6.42 (s, 1H), 4.912 (d, J=9.0 Hz, 0.5H), 4.906 (d, J=8.9 Hz, 0.5H), 4.67 (d, J=8.9 Hz, 0.5H), 4.66 (d, J=9.0 Hz, 0.5H), 4.53 (t, J=8.6 Hz, 2H), 4.03-3.44 (m, 6H), 3.35-3.17 (m, 2H), 3.00 (t, J=8.5 Hz, 2H), 2.77 (septet, J=6.9 Hz, 1H), 2.09-1.98 (m, 1H), 1.87-1.73 (m, 1H), 1.15 (d, J=5.7 Hz, 3H), 1.14 (d, J=6.0 Hz, 3H); 13C NMR (75 MHz, CDCl3) (diastereomers) δ178.33, 178.26, 162.0, 161.4, 156.3, 142.41, 142.36, 132.80, 132.75, 129.0, 124.25, 124.23, 123.6, 120.16, 120.10, 120.07, 118.9, 118.8, 108.4, 93.39, 93.36, 80.8, 72.5, 57.8, 49.2, 44.7, 44.6, 42.6, 42.5, 42.43, 42.40, 37.7, 37.5, 29.35, 29.32, 29.1, 23.7; MS (ES+) m/z 448.2 (M+1).
