4-Methylmorpholine → 6-({[3-(Trifluoromethyl)phenyl]acetyl}amino)pyridin-3-ylboronic acid

Participants

Reaction Conditions

Reaction Steps

A 250 mL round-bottomed flask was charged with 2-(3-(trifluoromethyl)phenyl)acetic acid (2.319 g, 11.36 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (2.5 g, 11.36 mmol), 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride (2.178 g, 11.36 mmol), 1-hydroxybenzotriazole hydrate (1.740 g, 11.36 mmol), N-methylmorpholine (5.00 mL, 45.4 mmol) and N,N-dimethylacetamide (50 mL). The reaction was stirred at 50° C. for 16 hours. The reaction was then quenched by the addition of ethyl acetate (50 mL) and water (50 mL). The layers were separated, and the organic was washed with water (3×50 mL) and brine (1×50 mL). The organic was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by reverse-phase HPLC using a 15% water (0.1% trifluoroacetic acid) to 95% acetonitrile (0.1% trifluoroacetic acid) gradient to give the boronic acid as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 3.88 (s, 2H), 7.54-7.66 (m, 3H), 7.72 (s, 1H), 7.96 (d, J=8.5 Hz, 1H), 8.12 (dd, J=1.7 and 8.1 Hz, 1H), 8.4 (br s, 1H), 10.94 (s, 1H).

Provenance & Evidence