Example 27
To the mixture of (1R,2S)-2-[3-([3-[(tert-butyldiphenylsilyl)oxy]-2,3-dihydro-1-benzofuran-7-yl]amino)-1H-indazol-6-yl]-5′-methoxy-1′H-spiro[cyclopropane-1,3′-indol]-2′-one (50.00 mg, 0.069 mmol, 1.00 equiv) in tetraethylene glycol (1.00 mL) was added KF (5.97 mg, 0.104 mmol, 1.50 equiv). The resulting mixture was stirred at 80° C. for 12 h. The mixture was purified by prep-HPLC with the following conditions: Column: XBridge Prep OBD C18 Column, 30×150 mm 5 μm; Mobile Phase A: Water (10 mmol/L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL/min; Gradient: 20% B to 38% B in 8 min; 254/220 nm; RT1: 7.63 min. The product-containing fractions were concentrated to give the title compound (15 mg, 45.7%) as a white solid. m/z (ESI, +ve ion)=455.10 [M+H]+. 1H NMR (400 MHz, Methanol-d4) δ 7.66-7.64 (m, 2H), 7.34 (s, 1H), 6.99 (d, J=7.2 Hz, 1H), 6.89-6.83 (m, 3H), 6.64-6.61 (m, 1H), 5.61 (s, 1H), 5.39-5.38 (m, 1H), 4.65-4.60 (m, 1H), 4.47-4.44 (m, 1H), 3.38-3.35 (m, 1H), 3.30 (s, 3H), 2.25-2.21 (m, 1H), 2.20-2.16 (m, 1H).
