反应详情

HATU (1.69 g, 4.45 mmol) was added to a stirring solution of 5-bromo-6-chloro-2-(4-fluorophenyl)furo[2,3-b]pyridine-3-carboxylic acid (1.1 g, 3.0 mmol), methylamine hydrochloride (1.00 g, 14.8 mmol), and DIEA (2.59 mL, 14.8 mmol) in a sealable tube in DMF (20 mL) at rt. The reaction tube was sealed and allowed to stir at rt for 2 hours. LCMS and TLC indicate complete conversion. The solution was then diluted with EtOAc (50 mL) and 1 M HCl (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic extracts were washed with water, brine, dried over Na2SO4, filtered and concentrated to give a tan solid. This solid was adsorbed onto SiO2 and eluted on silica gel with a 0-5% MeOH in DCM gradient over 40 CV (very slow gradient) to give 5-bromo-6-chloro-2-(4-fluorophenyl)-N-methylfuro[2,3-b]pyridine-3-carboxamide (1.1 g, 2.7 mmol, 92% yield) as a white fluffy solid. LCMS: m/e 385 (M+H)+ LCMS retention time: 3.04 min. (Column: Phenomenex-Luna 50×2.0 mm 3u. Solvent A=90% Water: 10% Methanol: 0.1% TFA. Solvent B=10% Water: 90% Methanol: 0.1% TFA. Start % B=0. Final % B=100. Gradient Time=4 min. Flow Rate=0.8 mL/min.). 1H NMR (500 MHz, CDCl3) δ ppm 8.50 (s, 1H), 7.89 (dd, J=9.0 Hz, 2H), 7.23 (dd, J=8.7 Hz, 2H), 5.85 (br s, 1H), 3.00 (d, J=4.8 Hz, 3H).

1. customThe reaction tube was sealed
2. customThe layers were separated
3. extractionthe aqueous layer was extracted with EtOAc (2×20 mL)
4. washThe combined organic extracts were washed with water, brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto give a tan solid
9. washeluted on silica gel with a 0-5% MeOH in DCM gradient over 40 CV (very slow gradient)