反应详情

2-(2-(3-Tert-butyl-4-formyl-1H-pyrazol-1-yl)acetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (1.66 g, 3.84 mmol) was dissolved in DCM (40 mL) and acetic acid (20.98 g, 20 mL, 349 mmol). Ethylamine (2M in THF, 7.68 mL, 15.35 mmol) was added and the mixture was stirred for 90 min. A slurry of palladium on charcoal (10%, 1.51 g, 1.420 mmol) in DCM (30 mL) was added and the mixture hydrogenated at 4 barr for 72 h at 20° C. The catalyst was filtered through dicalite and the dicalite washed with water, DCM and MeOH. All volatiles were removed under reduced pressure and the aqueous residue was basified to pH 8 using sodium bicarbonate. The crude product was extracted with EtOAc. The organics were combined and washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by chromatography (DCM, 0-30% MeOH/DCM and 0-20% 7 N NH3 in MeOH/DCM). Concentration in vacuo yielded a white solid (800 mg, 1.73 mmol, 45%).

1. waitthe mixture hydrogenated at 4 barr for 72 h at 20° C
2. filtrationThe catalyst was filtered through dicalite
3. washthe dicalite washed with water, DCM and MeOH
4. customAll volatiles were removed under reduced pressure
5. extractionThe crude product was extracted with EtOAc
6. washwashed with brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe crude material was purified by chromatography (DCM, 0-30% MeOH/DCM and 0-20% 7 N NH3 in MeOH/DCM)
11. concentrationConcentration in vacuo