Potassium Carbonate → 2-[4-(1-Hydroxy-1-methylethyl)phenyl]-5-{[6-(morpholin-4-ylmethyl)pyridin-2-yl]amino}-1,3-thiazole-4-carboxamide

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Reaction Steps

A sealed tube was charged with a stir bar, 5-amino-2-[4-(1-hydroxy-1-methylethyl)phenyl]-1,3-thiazole-4-carboxamide (150 mg, 0.54 mmol), Pd2(dba)3 (30 mg, 0.023 mmol), X-PHOS (77 mg, 0.16 mmol), and potassium carbonate (82 mg, 0.60 mmol). The tube was evacuated, and backfilled with argon three times. A second vial was charged with 4-[(6-bromopyridin-2-yl)methyl]morpholine (Example 2, Step 1) (139 mg, 0.54 mmol) and evacuated and backfilled with argon three times. Fully degassed tert-amyl alcohol (1.2 mL) was added to the vial containing 4-[(6-bromopyridin-2-yl)methyl]morpholine and the resulting solution was transferred by syringe to the tube containing the rest of the reagents. The reaction vessel was 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 (400 MHz CDCl3): δ 11.26 (s, 1H), 7.86 (d, 2H), 7.70 (s, 1H), 7.68 (d, 1H), 7.58 (s, 1H), 7.54 (d, 2H), 7.05 (d, 1H), 7.00 (d, 1H), 5.08 (s, 1H), 3.65 (s, 2H), 3.59 (m, 4H), 2.47 (m, 4H), 1.42 (s, 6H). LRMS (APCI) calc'd for C23H28N5O3S [M+H]+: 454.2, found 454.0.

Provenance & Evidence