反应详情

A suspension of Example B1 (0.074 g, 0.584 mmol) in DCE (6 mL) was treated with oxalyl chloride (0.051 mL, 0.584 mmol), stirred at RT for 30 min, then warmed to 83° C. for 3 h. The mixture was cooled to RT and added drop-wise to a solution of Example A2 (0.13 g, 0.486 mmol) in THF (6.0 mL) and pyridine (0.197 mL, 2.43 mmol). The mixture was stirred at RT for 1 h, treated with satd. NaHCO3, extracted with EtOAc (3×) and the combined organics were dried over MgSO4 and concentrated to dryness. The residue was triturated with MeCN, sonicated for 5 min and the solid was collected via filtration and dried to afford 3,3-dimethyl-N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)cyclobutanecarboxamide (125 mg, 61%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.11 (s, 1H), 10.70 (s, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.27-8.25 (m, 2H), 8.07 (d, J=9.0 Hz, 1H), 7.96 (d, J=0.7 Hz, 1H), 7.72 (dd, J=9.0, 2.9 Hz, 1H), 7.23 (d, J=2.4 Hz, 1H), 6.70 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 3.24 (m, 1H), 2.03-1.87 (m, 4H), 1.13 (s, 3H), 1.05 (s, 3H); MS (ESI) m/z: 421.2 (M+H+).

1. temperaturewarmed to 83° C. for 3 h
2. temperatureThe mixture was cooled to RT
3. stirringThe mixture was stirred at RT for 1 h
4. additiontreated with satd
5. extractionNaHCO3, extracted with EtOAc (3×)
6. dry with materialthe combined organics were dried over MgSO4
7. concentrationconcentrated to dryness
8. customThe residue was triturated with MeCN
9. customsonicated for 5 min
10. filtrationthe solid was collected via filtration
11. customdried