Reaction Steps
A mixture of (±)-(3S,4S)-4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidine-3,4-diol (42.00 mg, 0.0910 mmol), 1-fluoro-2-iodo-ethane (18.99 mg, 0.109 mmol), and sodium bicarbonate (9.174 mg, 0.109 mmol) in acetonitrile (1.000 mL, 19.15 mmol) was heated to reflux for overnight. After evaporation of volatiles under reduced pressure, the product was isolated by preparative reverse phase hplc (Gilson). Free base was obtained by catch/release work-up on acidic resin cartridge (Strata-X-C from Phenomenex) to afford (±)-(3S,4S)-1-(2-fluoro-ethyl)-4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidine-3,4-diol as a yellow foam (19 mg, 41%). 1H-NMR (CDCl3) δ 8.66 (s, 1H), 8.36 (d, J=8.4 Hz, 1H), 7.93 (d, J=7.6 Hz, 1H), 7.45 (m, 2H), 7.11 (m, 3H), 7.01 (d, J=4.6 Hz, 1H), 6.95 (d, J=8.5 Hz, 1H), 6.83 (d, J=4.6 Hz, 1H), 4.67 (m, 1H), 4.56 (m, 1H), 4.19 (dd, J=10.0; 4.8 Hz, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.00 (m, 1H), 2.85 (m, 1H), 2.75 (m, 3H), 2.55 (m, 1H), 2.44 (m, 1H), 2.07 (m, 1H), 1.90 (br s, 1H), 1.87 (m, 1H); LC/MS (ESI+): 508.0 (M+H).
