反应详情

To 4-methyl-7H-pyrrolo[2,3-d]pyrimidine (42, 0.192 g, 1.44 mmol), propane-1-sulfonic acid (2,4-difluoro-3-formyl-phenyl)-amide (9, 0.456 g, 1.73 mmol), potassium hydroxide (0.263 g, 4.69 mmol) and 1.0 mL of methanol were added to provide a solution. The reaction was allowed to stir at room temperature for 30 hours, then quenched with water and adjusted to pH ˜5 with acetic acid and sodium bicarbonate and extracted with ethyl acetate and saturated sodium chloride. The organic layer was washed with water and brine, dried with magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with ethyl acetate and hexane with 4% acetic acid. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound as an off-white solid (P-0055, 215 mg). 1H-NMR(dmso-d6) showed it contains about >80% of the desired compound, used in the next step without further purification. MS(ESI) [M+H−]+=397.1.

1. customto provide a solution
2. customquenched with water
3. extractionextracted with ethyl acetate and saturated sodium chloride
4. washThe organic layer was washed with water and brine
5. dry with materialdried with magnesium sulfate
6. filtrationfiltered
7. concentrationthe filtrate concentrated under vacuum
8. customThe resulting material was purified by silica gel column chromatography
9. washeluting with ethyl acetate and hexane with 4% acetic acid
10. concentrationconcentrated under vacuum