反应详情

To a solution of Intermediate AW (N-{4-[4-amino-7-formyl-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoro-methyl)phenyl]urea (25 mg, 0.05 mmol)) in THF (1 ml) at −78 C under N2 was added methyllithium (0.18 ml, 0.25 mmol) and stirred for 10 min. The reaction was quenched by the addition of H2O and after warming to rt, the reaction mixture was extracted with ethyl acetate. The organic layer was dried (Na2SO4), concentrated and purified via column chromatography (5:95 v/v MeOH—CH2Cl2) to afford 13 mg of the title compound (yield 50%). 1H-NMR (DMSO-d6) δ9.32 (s, 1H), 8.97 (d, J=2 Hz, 1H), 8.63 (dd, J=8, 2 Hz, 1H), 7.87 (s, 1H), 7.55 (d, J=8 Hz, 2H), 7.53 to 7.31 (m, 4H), 5.49 to 5.45 (m, 1H), 5.19 (d, J=6 Hz, 1H), 4.52 (d, J=10 Hz, 1H), 4.19 (d, J=10 Hz, 1H), 3.16 (s, 3H), 1.50 (d, J=6 Hz, 3H) ppm; MS [M+H]+=519.1; LCMS RT=2.74 min.

1. customThe reaction was quenched by the addition of H2O
2. extractionthe reaction mixture was extracted with ethyl acetate
3. dry with materialThe organic layer was dried (Na2SO4)
4. concentrationconcentrated
5. custompurified via column chromatography (5:95 v/v MeOH—CH2Cl2)