Potassium Carbonate → 2-(4-Chlorophenyl)-5-{[6-(morpholin-4-ylmethyl)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 (Example 1, Step 1) (83 mg, 0.33 mmol), 4-[(6-bromopyridin-2-yl)methyl]morpholine (84 mg, 0.33 mmol), Pd2(dba)3 (9 mg, 0.01 mmol), X-PHOS (23 mg, 0.05 mmol), and potassium carbonate (50 mg, 0.36 mmol). The tube was evacuated, and backfilled with argon three times. Fully degassed tert-amyl alcohol (0.8 mL) was added to the reaction vessel, which was sealed and left to stir at 100° C. overnight. The reaction vessel was cooled to room temperature, taken up in ethyl acetate and washed with 100 mL saturated aqueous sodium bicarbonate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated into a sealed tube. To the tube was charged Pd2(dba)3 (18 mg, 0.02 mmol), X-PHOS (46 mg, 0.1 mmol), and potassium carbonate (100 mg, 0.72 mmol). The tube was evacuated, and backfilled with argon three times. Fully degassed tert-amyl alcohol (0.8 mL) was added to the reaction vessel, which was sealed and left to stir at 100° C. overnight. The reaction vessel was cooled to room temperature, taken up in ethyl acetate and washed with 100 mL saturated aqueous sodium bicarbonate. The organic layer was dried over anhydrous magnesium sulfate and filtered. To the filtrate was added 1.0 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 11.29 (s, 1H), 7.96 (d, 2H), 7.79 (s, 1H), 7.70 (t, 1H), 7.60 (s, 1H), 7.53 (d, 2H), 7.07 (d, 1H), 7.02 (d, 1H), 3.67 (s, 2H), 3.59 (m, 4H), 2.46 (m, 4H). LRMS (APCI) calc'd for C20H21ClN5O2S [M+H]+: 430.1, found 430.0.

Provenance & Evidence