反应详情

温度

80 °C

N-{6-Bromo-1-[(4-methylphenyl)sulfonyl]-1H-indazol-4-yl}-2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-thiazole-4-carboxamide (4 g), 2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinamine (1.8 g), sodium carbonate (2.8 g) and Pd(dppf)Cl2 (0.48 g) were weighed to a 500 ml round-bottomed flask and 1,4-dioxane (150 ml) and water (150 ml) were added. The reaction was heated to 80° C. for 2 hours. The reaction was cooled then passed through a 10 g silica cartridge, washing with DCM:methanol. The reaction was concentrated to leave only the aqueous phase. DCM was added and the product extracted. The DCM was passed through a hydrophobic frit, then evaporated to dryness. The residue was purified on silica chromatography eluting with 0-6% methanol in DCM over 30 mins. Product containing fractions were combined and evaporated to dryness. The residue was repurified by silica chromatography using a gradient of 1.5-5% methanol in DCM over 30 mins. Product containing fractions were combined and evaporated to dryness to give title compound (1.9 g).

1. temperatureThe reaction was cooled
2. washwashing with DCM
3. concentrationThe reaction was concentrated
4. customto leave only the aqueous phase
5. extractionthe product extracted
6. customevaporated to dryness
7. customThe residue was purified on silica chromatography
8. washeluting with 0-6% methanol in DCM over 30 mins
9. additionProduct containing fractions
10. customevaporated to dryness
11. customThe residue was repurified by silica chromatography
12. customover 30 mins
13. additionProduct containing fractions
14. customevaporated to dryness