反应详情

Methanesulfonyl chloride (13 L, 0.16 mmol) and triethylamine (34 μL, 0.24 mmol) were added to a solution of ethyl 2-[3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]-4-hydroxy-butanoate (Intermediate 28) (65 mg, 0.12 mmol) in DCM (5 mL) at 0° C. under nitrogen. The reaction was allowed to warm to RT and stirred for 2 hours. The solvent was evaporated under reduced pressure and the residue partitioned between ethyl acetate (10 mL) and brine (10 mL). The organic layer was separated and the aqueous layer re-extracted with ethyl acetate (10 mL). The combined organics were dried (MgSO4), concentrated under reduced pressure and the residue purified by column chromatography on silica eluting with 0-10% methanol/DCM to give product (29 mg, 42%). 1H NMR δ (300 MHz, CDCl3) 1.23-1.30 (3H, m), 2.33-2.46 (4H, m), 2.56 (3H, s), 3.03 (3H, s), 4.22-4.29 (4H, m), 4.44-4.49 (2H, m), 4.71 (2H t), 4.87-4.91 (1H, m), 6.81 (1H t), 7.21 (1H t), 7.29 (1H t), 7.38-7.41 (1H, m), 8.13 (2H d), 8.34 (1H d), 8.42 (1H, s), 9.51 (1H, s); m/z 615 (M+H)+.

1. customThe solvent was evaporated under reduced pressure
2. customthe residue partitioned between ethyl acetate (10 mL) and brine (10 mL)
3. customThe organic layer was separated
4. extractionthe aqueous layer re-extracted with ethyl acetate (10 mL)
5. dry with materialThe combined organics were dried (MgSO4)
6. concentrationconcentrated under reduced pressure
7. customthe residue purified by column chromatography on silica eluting with 0-10% methanol/DCM