反应详情

温度

100 °C

The product of Step 5 (174 mg, 0.61 mmol), N-[3-nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (INTERMEDIATE 12, 250 mg, 0.61 mmol), and PdCl2(dppf).CH2Cl2 (44.6 mg, 0.061 mmol) were combined in a flask, sealed, and purged with nitrogen (2×). Dioxane (3.6 mL) and 2 M Na2CO3 (0.91 mL, 1.83 mmol) were added, and the reaction was purged again with nitrogen (2×). The mixture was stirred in an oil bath at 100° C. for 4 h. The dark brown reaction was diluted with water and extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated. Flash chromatography (dry load, 20-100% ethyl acetate in hexanes) afforded 220 mg (74%) of 2-[5-(3-nitro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propane-2-sulfonamide as a yellow solid. ESI: [M+H]+ m/z 489.0. 1H NMR (500 MHz, DMSO-d6) δ 10.80 (s, 1H), 8.94 (d, J=4.9, 1H), 8.72 (s, 1H), 8.48 (s, 1H), 8.33 (s, 1H), 8.14 (s, 1H), 7.43 (d, J=4.9, 1H), 7.10 (s, 2H), 1.81 (s, 6H). rhSYK activity=++

1. customsealed
2. custompurged with nitrogen (2×)
3. customthe reaction was purged again with nitrogen (2×)
4. customThe dark brown reaction
5. extractionextracted with ethyl acetate (2×)
6. washThe combined organic layers were washed with brine
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. customevaporated
10. dry with materialFlash chromatography (dry load, 20-100% ethyl acetate in hexanes)