Potassium Carbonate → 2-(4-Chlorophenyl)-5-{[5-(1-hydroxy-1-methylethyl)pyridin-2-yl]amino}-1,3-thiazole-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

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

Provenance & Evidence