反应详情

温度

100 °C

A sealed tube was charged with a stir bar, 5-amino-2-(4-chlorophenyl)-1,3-thiazole-4-carboxamide (150 mg, 0.59 mmol), 2-(6-bromopyridin-3-yl)propan-2-ol (for preparation, see WO 2004/050024 A2 Example 120 Step A) (128 mg, 0.59 mmol), Pd2(dba)3 (33 mg, 0.035 mmol), X-PHOS (85 mg, 0.177 mmol), and potassium carbonate (90 mg, 0.65 mmol). The tube was evacuated, and backfilled with argon three times. Fully degassed tert-amyl alcohol (1.2 mL) was added to the reaction vessel, which was sealed and left to stir at 100° C. overnight. The reaction vessel was removed then cooled to room temperature, and the crude 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 combined organic extracts were dried over anhydrous magnesium sulfate, and filtered. To the filtrate was added 1.5 g of silica gel and the solvent was removed in vacuo. The compound on silica was purified via flash chromatography (silica, 0-3% methanol/ethyl acetate) to afford the title compound. 1H NMR (500 MHz, d6-DMSO): δ 11.26 (s, 1H), 8.24 (d, 1H), 7.98 (d, 2H), 7.82 (m, 2H), 7.73 (s, 1H), 7.35 (d, 2H), 7.17 (d, 1H), 5.14 (s, 1H), 1.44 (s, 6H). LRMS (APCI) calc'd for C18H18ClN4O2S [M+H]+: 389.1, found 389.0

1. additionA sealed tube was charged with a stir bar
2. customThe tube was evacuated
3. additionFully degassed tert-amyl alcohol (1.2 mL) was added to the reaction vessel, which
4. customwas sealed
5. waitleft
6. customThe reaction vessel was removed
7. temperaturethen cooled to room temperature
8. customthe crude reaction mixture
9. washwashed with 100 mL water
10. additionThe water layer was treated with concentrated ammonium hydroxide
11. extractionextracted with ethyl acetate
12. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
13. filtrationfiltered
14. additionTo the filtrate was added 1.5 g of silica gel
15. customthe solvent was removed in vacuo
16. customThe compound on silica was purified via flash chromatography (silica, 0-3% methanol/ethyl acetate)