Potassium Carbonate → 2-(4-Chlorophenyl)-5-{[6-(2-hydroxy-1-morpholin-4-ylethyl)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) (247 mg, 0.97 mmol), Pd2(dba)3 (54 mg, 0.058 mmol), X-PHOS (139 mg, 0.29 mmol), and potassium carbonate (148 mg, 1.07 mmol). The tube was evacuated, and backfilled with argon three times. A second vial was charged with racemic 2-(6-bromopyridin-2-yl)-2-morpholin-4-ylethanol (280 mg, 0.97 mmol) and evacuated and backfilled with argon three times. Fully degassed tert-amyl alcohol (2.3 mL) was added to the vial containing 2-(6-bromopyridin-2-yl)-2-morpholin-4-ylethanol and the resulting solution was transferred by syringe to the tube containing the rest of the reagents. This vial was sealed and left to stir at 100° C. overnight. 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 organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Purification via flash chromatography (silica, 0-3% methanol/ethyl acetate) afforded the title compound. 1H NMR (600 MHz, d6-DMSO): δ 11.28 (s, 1H), 7.94 (d, 2H), 7.79 (s, 1H), 7.69 (t, 1H), 7.61 (s, 1H), 7.54 (d, 2H), 7.07 (d, 1H), 6.94 (d, 1H), 4.51 (t, 1H), 4.00 (m, 1H), 3.92 (m, 1H), 3.65 (t, 1H), 3.52 (m, 4H), 2.48 (m, 4H). LRMS (APCI) calcd for C21H22ClN5O3S [M+H]+: 460.1, found 460.0

Provenance & Evidence