Tetrahydrofuran → HCID 57955165, compound

Participants

Reaction Steps

To a solution of Example 23 (N-{4-[4-amino-7-(hydroxymethyl)-6-(methoxy-methyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoro-methyl)-phenyl]urea (22 mg, 0.04 mmol)) in anhydrous THF (1 mL) and CH2Cl2 (1 mL) was added SOCl2 (0.006 ml, 0.08 mmol). After 20 min, analytical HPLC shoved half of the starting material remained. Additional SOCl2 (0.01 ml) was added and the reaction was stirred at rt for 2.5 h until completion. The mixture was evaporated to dryness and CH2Cl2 (3 ml) was added. The solvent was evaporated to dryness and the crude concentrate was re-suspended in CH2Cl2 and evaporated to remove the excess SOCl2 completely. To the resulting solid was added anhydrous MeOH (1 ml) and Hunig's base (0.008 ml), the reaction was stirred at 70° C. overnight. After 16 h, the reaction was cooled to rt and solvent was evaporated. The crude material was taken up in ethyl acetate, washed with aq. saturated sodium bicarbonate three times and dried over Na2SO4. After concentration, the resulting crude was purified via column chromatography (5:95 v/v MeOH—CH2Cl2) to afford 12 mg of the title compound (yield 53%). 1H-NMR (DMSO-d6) δ 9.32 (s, 1H), 8.96 (d, J=3 Hz, 1H), 8.63 (dd, J=7, 3 Hz, 1H), 7.92 (s, 1H), 7.59 (t, J=3 Hz, 2H), 7.57 to 7.32 (m, 4H), 4.73 (s, 2H), 4.28 (s, 2H), 3.26 (s, 3H), 3.24 (s, 3H) ppm; MS [M+H]+=519.1; LCMS RT=2.84 min

Provenance & Evidence