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0 °C

In a 25 ml, 3-neck RBF equipped with a calcium chloride guard tube, to a solution of tert-butyl (5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)(3-(N-hydroxyacrylamido)phenyl)carbamate (0.250 g) in DCM (10 ml) was added trifluoroacetic acid (5.0 ml) drop wise into the reaction mixture at 0° C. The reaction mixture was stirred at 0° C. for 15 minutes and then at room temperature for 30 minutes. The reaction was monitored by TLC using hexane:ethyl acetate (3:7) as mobile phase. After completion of the reaction, the reaction mixture was quenched in water and neutralized with sodium bicarbonate. Product was extracted into DCM and the organic layer was washed with brine, dried over sodium sulfate and concentrated completely under reduce pressure at 40° C. Crude material was purified by preparative-HPLC to give 8.3 mg of N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-N-hydroxyacrylamide. 1H NMR: DMSO-d6 (400 MHz): 3.236-3.208 (t, 2H, J=8), 3.356 (s, 3H), 3.628-3.250 (t, 2H, J=4.4), 4.018-4.040 (t, 2H, J=4.4), 4.488-4.528 (t, 2H, J=8), 6.798 (d, 2H, J=8.8), 7.35 (d, 2H, J=6.4), 7.72 (d, 2H, J=6), 7.84 (s, 1H), 8.085 (d, 1H, J=3.6), 9.011 (s, 1H), 9.457 (s, 1H).

1. waitat room temperature for 30 minutes
2. customAfter completion of the reaction
3. customthe reaction mixture was quenched in water and neutralized with sodium bicarbonate
4. extractionProduct was extracted into DCM
5. washthe organic layer was washed with brine
6. dry with materialdried over sodium sulfate
7. concentrationconcentrated completely
8. customat 40° C
9. customCrude material was purified by preparative-HPLC