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

Participants

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 (Example 5, Step 3) (60 mg, 0.22 mmol), Pd2(dba)3 (5.9 mg, 6.5 μmol), X-PHOS (15.5 mg, 0.032 mmol), and potassium carbonate (33 mg, 0.24 mmol). The tube was evacuated and backfilled with argon three times. 2-(6-bromopyridin-2-yl)-2-morpholin-4-ylethanol (Example 3, Step 1) (62 mg, 0.22 mmol) was placed in a separate vial which was also evacuated and backfilled with argon three times. Fully degassed tert-amyl alcohol (500 μl) was added to 2-(6-bromopyridin-2-yl)-2-morpholin-4-ylethanol and the resulting solution was transferred to the sealed tube via syringe. The tube was then sealed and placed in an oil bath at 100° C. and stirred overnight. The reaction was cooled to room temperature, diluted with ethyl acetate, and washed with saturated aqueous sodium bicarbonate (2×) and brine (2×). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification was performed by reverse phase HPLC (10-100% acetonitrile/water+0.05% TFA modifier, monitoring at 230 nM). Desired fractions were poured into a mixture of ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was extracted, dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the title compound as a light yellow powder. 1H NMR (500 MHz, d6-DMSO) δ 11.25 (s, 1H), 7.84 (d, 2H), 7.70 (s, 1H), 7.68 (t, 1H), 7.59 (s, 1H), 7.55 (d, 2H), 7.05 (d, 1H), 6.92 (d, 1H), 5.08 (s, 1H), 4.51 (t, 1H), 3.98 (m, 2H), 3.65 (t, 1H), 3.53 (m, 4H), 3.75 (m, 4H), 3.42 (s, 6H). LRMS (APCI) calc'd for (C24H30N5O4S) [M+H]+, 484.2; found 484.1.

Provenance & Evidence