反应详情

To the solution of 3-((S)-3-azido-6-cyclohexyl-2-oxo-piperidin-1-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (40 mg, 0.09 mmol, 1 equiv) in MeOH (0.5 mL) was added SnCl2 (17 mg, 0.09 mmol, 1 equiv) and the resulting solution was stirred at room temperature for 18 hours. The solvent was then removed under vacuum. The residue was dissolved in THF/H2O/MeOH (0.5 mL/0.5 mL/1.0 mL) and to the solution was added LiOH.H2O (21 mg, 0.48 mmol, 5 equiv). The reaction mixture was stirred at 50° C. for 20 minutes. The organic solvents were removed under vacuum and the residue was acidified to pH=5 by addition of 3.0 N HCl aq. solution. The mixture was extracted with EtOAc. The organic layer was dried over Na2SO4, and concentrated under vacuum. The residue was purified by prep-HPLC (XBridge Prep C 18 5 um, 30×50 mm) in basic condition (0.1% NH4OH, 10%˜45% CH3CN/H2O, 10 min run, 40 ml/min) to give product 12 mg. MS: 403 [M+H+]. 1H-NMR (400 MHZ, CD3OD): δ 6.81 (s, 1H), 3.96 (br, 1H), 3.48 (m, 1H), 2.06 (m, 3H), 1.84 (m, 3H), 1.70 (br, 2H), 1.46 (m, 1H), 1.37 (m, 1H), 1.31 (s, 9H), 1.16 (m, 5H).

1. customThe solvent was then removed under vacuum
2. dissolutionThe residue was dissolved in THF/H2O/MeOH (0.5 mL/0.5 mL/1.0 mL) and to the solution
3. stirringThe reaction mixture was stirred at 50° C. for 20 minutes
4. customThe organic solvents were removed under vacuum
5. additionthe residue was acidified to pH=5 by addition of 3.0 N HCl aq. solution
6. extractionThe mixture was extracted with EtOAc
7. dry with materialThe organic layer was dried over Na2SO4
8. concentrationconcentrated under vacuum
9. customThe residue was purified by prep-HPLC (XBridge Prep C 18 5 um, 30×50 mm) in basic condition (0.1% NH4OH, 10%˜45% CH3CN/H2O, 10 min run, 40 ml/min)