反应详情

To a mixture of 5-[1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-5-methyl-1H-pyrazol-4-yl]-3-[1-(2,6-dichloro-3-fluorophenyl)-2-fluoro-2,2-bis(phenylsulfonyl)ethyl]-1H-pyrrolo[2,3-b]pyridine (30.00 mg, 0.03333 mmol) and Disodium hydrogen phosphate (94.64 mg, 0.6667 mmol) in methanol (5.00 mL, 123 mmol) and THF (0.300 mL, 3.70 mmol) at −20° C. was added Sodium Mercury Amalgam (5% sodium; 0.28 g, 0.67 mmol). The resulting mixture was stirred between −15° C. and −5° C. for 1.5 h. The mixture was transferred into another flask by filtration to remove the inorganic insolubles. Sat. aq. solution of NH4Cl (2 ml) was added to the MeOH mixture, then the solvent was removed under reduced pressure to give a residue, which was diluted by DCM and extracted by DCM (20 mL×3). The organic phase were combined, dried and concentrated to give a desulfonylated intermediate [MS (ES+): m/z 619.23, 621.23 [MH+]. HPLC: tR=2.02 min (polar—3 min, TOF)]. This intermediate was dissolved in THF (0.3 mL) at 0° C., 2.0 M aq. HCl (0.50 mL, 1.0 mmol) was added, and the resulting mixture was stirred at rt for 30 min. NaHCO3 (112.0 mg, 1.333 mmol) was added to the mixture slowly to adjust pH=≈9. Then the solvent was removed under reduced pressure to give a residue, which was diluted by DCM and extracted by DCM (20 mL×3). The organic phase were combined, dried and concentrated to give a crude residue which was purified by silica gel chromatography (eluent: 5% MeOH in DCM) to give the title compound. 1H NMR (400 MHz, CD3OD): δ=1.48-1.60 (m, 2H), 1.94-2.16 (m, 6H), 2.26 (s, 3H), 3.63-3.77 (m, 1H), 4.15-4.28 (m, 1H), 5.20-5.54 (m, 2H), 5.62-5.75 (m, 1H), 7.28 (t, J=8.6 Hz, 1H), 7.35-7.64 (m, 4H), 8.20 (d, J=2.0 Hz, 1H). MS (ES+): m/z 505.06, 507.07 [MH+]. HPLC: tR=1.33 min (polar—3 min, TOF).

1. filtrationThe mixture was transferred into another flask by filtration
2. customto remove the inorganic insolubles
3. additionSat. aq. solution of NH4Cl (2 ml) was added to the MeOH mixture
4. customthe solvent was removed under reduced pressure
5. customto give a residue, which
6. extractionextracted by DCM (20 mL×3)
7. customdried
8. concentrationconcentrated
9. customto give a desulfonylated intermediate [MS (ES+): m/z 619.23, 621.23 [MH+]. HPLC: tR=2.02 min (polar—3 min, TOF)]
10. stirringthe resulting mixture was stirred at rt for 30 min
11. customThen the solvent was removed under reduced pressure
12. customto give a residue, which
13. extractionextracted by DCM (20 mL×3)
14. customdried
15. concentrationconcentrated
16. customto give a crude residue which
17. customwas purified by silica gel chromatography (eluent: 5% MeOH in DCM)