反应详情

温度

100 °C

A sealed tube was charged with a stir bar, 5-amino-2-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-1,3-thiazole-4-carboxamide (52 mg, 0.17 mmol), 2-(6-chloropyridazin-3-yl)propan-2-ol (29 mg, 0.17 mmol), Pd2(dba)3 (15 mg, 0.017 mmol), X-PHOS (40 mg, 0.083 mmol), and potassium carbonate (23 mg, 0.17 mmol). The tube was evacuated and backfilled with argon 3×. Fully degassed tert-amyl alcohol (0.33 ml) was added and the reaction vessel was sealed and left to stir at 100° C. overnight. The reaction vessel was removed from the heat and allowed to cool to room temperature. The reaction mixture was taken up in ethyl acetate and washed with 100 mL water. The water layer was treated with concentrated ammonium hydroxide and extracted with ethyl acetate. The organic fractions were combined, dried over anhydrous magnesium sulfate, and filtered. To the organic layer was added 0.45 g of silica gel and the solvent was removed under reduced pressure. The compound on silica was purified by flash chromatography (500 ml gradient of 0-3% methanol/ethyl acetate) to afford the title compound as a light yellow solid. 1H NMR (500 MHz, d6-DMSO) δ 11.41 (s, 1H), 7.83 (d, 1H), 7.74 (s, 1H), 7.68 (d, 1H), 7.57 (s, 1H), 7.34 (d, 2H), 5.42 (s, 1H), 5.38 (s, 1H), 1.50 (s, 6H), 1.44 (s, 6H). LRMS (APCI) calcd for C20H22F2N5O3S [M+H]+ 450.1, found 450.0.

1. additionA sealed tube was charged with a stir bar
2. customThe tube was evacuated
3. additionFully degassed tert-amyl alcohol (0.33 ml) was added
4. customthe reaction vessel was sealed
5. waitleft
6. customThe reaction vessel was removed from the
7. temperatureheat
8. temperatureto cool to room temperature
9. washwashed with 100 mL water
10. additionThe water layer was treated with concentrated ammonium hydroxide
11. extractionextracted with ethyl acetate
12. dry with materialdried over anhydrous magnesium sulfate
13. filtrationfiltered
14. additionTo the organic layer was added 0.45 g of silica gel
15. customthe solvent was removed under reduced pressure
16. customThe compound on silica was purified by flash chromatography (500 ml gradient of 0-3% methanol/ethyl acetate)