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

Temperature

50 °C

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, 2 H), 7.54-7.66 (m, 3 H), 7.72 (s, 1 H), 7.96 (d, J=8.5 Hz, 1 H), 8.12 (dd, J=1.7 and 8.1 Hz, 1 H), 8.4 (br s, 1 H), 10.94 (s, 1 H).

1. customThe reaction was then quenched by the addition of ethyl acetate (50 mL) and water (50 mL)
2. customThe layers were separated
3. washthe organic was Washed with water (3×50 mL) and brine (1×50 mL)
4. dry with materialThe organic was dried with anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by reverse-phase

ORD record

ord-066f1e9aef794aeea38d7aac270a5dfc

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901152B2