反应详情

A suspension of 2,2,2-trimethylacetamide (0.086 g, 0.850 mmol) in DCE (3.5 mL) was treated drop-wise with oxalyl chloride (0.074 mL, 0.850 mmol), stirred at RT for 0.5 h, then warmed to 85° C. for 1 h. The solution was cooled to RT, added drop-wise to a solution of Example A7 (0.2 g, 0.708 mmol) and pyridine (0.069 mL, 0.850 mmol) in THF (3.5 mL) and stirred at RT for 2.5 days. Satd. NaHCO3 was added, the mixture extracted with EtOAc (4×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The white solid was dissolved in MeOH, treated with water until a precipitate formed and the solid was collected via filtration, dissolved in MeCN/H2O, frozen and lyophilized to afford N-((6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (51 mg, 18%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.16 (s, 1H), 10.41 (s, 1H), 8.55 (d, J=5.7 Hz, 1H), 7.93-7.91 (m, 1H), 7.69 (d, J=8.8 Hz, 1H), 7.34 (d, J=2.5 Hz, 1H), 6.97-6.95 (m, 2H), 2.28 (s, 3H), 2.25 (s, 3H), 1.20 (s, 9H); MS (ESI) m/z: 410.2 (M+H+).

1. temperaturewarmed to 85° C. for 1 h
2. temperatureThe solution was cooled to RT
3. stirringstirred at RT for 2.5 days
4. extractionthe mixture extracted with EtOAc (4×)
5. dry with materialthe combined organics were dried over Na2SO4
6. concentrationconcentrated to dryness
7. custompurified via silica gel chromatography (MeOH/DCM)
8. dissolutionThe white solid was dissolved in MeOH
9. additiontreated with water until a precipitate
10. customformed
11. filtrationthe solid was collected via filtration
12. dissolutiondissolved in MeCN/H2O
13. temperaturefrozen