反应详情

温度

140 °C

Tripotassium phosphate (910 mg, 4.29 mmol), chloro[2′-(dimethylamino)-2-biphenylyl]palladium-(1R,4S)-bicyclo[2.2.1]hept-2-yl[(1S,4R)-bicyclo[2.2.1]hept-2-yl]phosphane (1:1) (105 mg, 0.143 mmol) and 2-(methyloxy)-5-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-3-pyridinamine (453 mg, 1.715 mmol) were weighed to a 20 ml microwave vial. N-[6-Bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-thiazole-4-carboxamide (764 mg, 1.429 mmol) was dissolved in 1,4-dioxane (10 mL) and added, followed by water (2.000 mL). The reaction was heated at 140° C. for 20 min. The reaction mixture was passed through a 10 g silica cartridge, eluting with methanol. The solvent was evaporated to dryness and the residue was partitioned between DCM 200 ml and water 200 ml. The DCM was collected and eluted through a hydrophobic frit, then evaporated to dryness. The residue was purified by chromatography on silica gel (100 g cartridge), eluting with 0-25% methanol in DCM over 40 mins, then on a further silica gel 100 g cartridge, eluting with 0-100% ethyl acetate in cyclohexane over 40 mins and then 0-25% methanol in DCM over 20 mins to afford the title compound (512 mg).

1. additionadded
2. washeluting with methanol
3. customThe solvent was evaporated to dryness
4. customthe residue was partitioned between DCM 200 ml and water 200 ml
5. customThe DCM was collected
6. washeluted through a hydrophobic frit
7. customevaporated to dryness
8. customThe residue was purified by chromatography on silica gel (100 g cartridge)
9. washeluting with 0-25% methanol in DCM over 40 mins
10. washon a further silica gel 100 g cartridge, eluting with 0-100% ethyl acetate in cyclohexane over 40 mins