反应详情

Ethyl 2-[3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]-4-methylsulfonyloxy-butanoate (Intermediate 27) (27 mg, 0.04 mmol), sodium iodide (7 mg, 0.04 mmol) and ethylamine (2M in THF; 45 μL, 0.09 mmol) in acetonitrile (2 mL) were heated in a microwave at 120° C. for 90 minutes. Solvent evaporated under reduced pressure and the residue diluted with ethyl acetate (20 mL) and brine (20 mL). The organics were separated and the aqueous layer re-extracted with ethyl acetate (20 mL). The combined organics were dried (MgSO4) and concentrated and the residue purified by preparative HPLC, eluting with a gradient of 5 to 95% acetonitrile in water containing 0.2% trifluoroacetic acid on a Phenomenex Luna 10u C18(2) 100A column, to afford product (24 mg, 87%). 1H NMR δ (300 MHz, CDCl3) 1.19 (3H, t), 2.17-2.26 (1H, m), 2.34-2.44 (2H, m), 2.62-2.74 (4H, m), 3.39-3.59 (4H, m), 4.30 (2H, s), 4.76 (2H, s), 5.11 (1H, t), 6.95 (1H, t), 7.29 (1H, t), 7.39-7.42 (1H, m), 7.52 (1H, d), 8.10 (1H, d), 8.19 (1H, s), 8.36 (1H, d), 9.65 (1H, d); m/z 517 (M+H)+.

1. customSolvent evaporated under reduced pressure
2. additionthe residue diluted with ethyl acetate (20 mL) and brine (20 mL)
3. customThe organics were separated
4. extractionthe aqueous layer re-extracted with ethyl acetate (20 mL)
5. dry with materialThe combined organics were dried (MgSO4)
6. concentrationconcentrated
7. customthe residue purified by preparative HPLC
8. washeluting with a gradient of 5 to 95% acetonitrile in water containing 0.2% trifluoroacetic acid on a Phenomenex Luna 10u C18(2) 100A column