Reaction Steps
Trifluoro-methanesulfonic acid 7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester (320.00 mg, 0.857 mmol), N,N-Diisopropylethylamine (0.779 mL, 4.47 mmol), and (S)-3-[4-(4-Amino-3-methoxy-phenyl)-piperidin-1-yl]-propane-1,2-diol (600.65 mg, 2.142 mmol) were dissolved in 1-methoxy-2-propanol (2.3 mL) and the reaction mixture was heated at 100° C. for 8 h. The reaction mixture was partitioned between dichloromethane and saturated aqueous NaHCO3, and the organic layer was separated and dried over MgSO4, then filtered. The solvent was evaporated under reduced pressure and the product was isolated by column chromatography (ISCO, Silicagel, methanol/dichloromethane 0-10%). The product needed to be further purified by preparative reverse phase HPLC (Gilson, 0.1% TFA water/acetonitrile gradient) followed by neutralization of the resulting TFA salt to afford (S)-3-(4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-propane-1,2-diol as a light orange solid (115 mg, 27%). MP: 66-80° C.; 1H-NMR (CDCl3) δ 8.69 (s, 1H), 8.29 (d, J=8.0 Hz, 1H), 8.99 (dd, J=8.0, 1.6 Hz, 1H), 7.44 (m, 2H), 7.13 (m, 1H), 7.07 (d, J=8.0 Hz, 1H), 7.02 (d, J=4.7 Hz, 1H), 6.83 (d, J=4.7 Hz, 1H), 6.72 (s, 1H), 6.71 (d, J=8.0 Hz, 1H), 3.90 (s, 3H), 3.86 (m, 1H), 3.85 (s, 3H), 3.77 (m, 1H), 3.55 (m, 1H), 3.22 (d, J=10.6 Hz, 1H), 3.08 (d, J=10.6 Hz, 1H), 2.77 (br s, 2H), 2.69 (m, 1H), 2.48 (m, 3H), 2.20 (m, 1H), 1.85 (m, 4H); LC/MS (ESI+): 504.19 (M+H).
