反应详情

温度

40 °C

A mixture of 3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-ylboronic acid prepared as above (6.0 g, 18.8 mmol, 90%), (R)-6-chloro-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (3.63 g, 12.5 mmol) (similarly prepared as described in Example 4, Step A), tri-tert-butylphosphonium tetrafluoroborate (0.36 g, 1.2 mmol), Pd2(dba)3 (0.57 g, 0.62 mmol) and potassium fluoride (7.25 g, 125 mmol) in THF (80 mL) was stirred at 40° C. overnight. The solvent was then evaporated and the residue purified on silica gel eluting with a gradient of 0 to 10% ethyl acetate in CH2Cl2 to provide (R)-6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (5.83 g, 94%). Melting point: 191-193° C.; MS m/z 495.0 M+H+; 1H NMR (500 MHz, CDCl3): δ 9.24 (1H, t, J=1.1 Hz), 8.34 (1H, dd, J=8.3 Hz, J=2.4 Hz), 8.05 (1H, dd, J=8.3, 0.7 Hz), 7.43 (1H, d, J=9.2 Hz), 7.37 (1H, d, J=6.0 Hz), 5.26-5.19 (2H, m), 4.20-4.12 (1H, m), 2.46 (3H, d, J=1.9 Hz), 2.31-2.26 (2H, m), 2.20-2.16 (2H, m), 2.07-2.04 (2H, m), 1.80-1.76 (2H, m), 1.45 (3H, d, J=7.0 Hz).

1. customsimilarly prepared
2. customThe solvent was then evaporated
3. customthe residue purified on silica gel eluting with a gradient of 0 to 10% ethyl acetate in CH2Cl2