反应详情

A solution of chiral (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-2-(1-hydroxycarbonyl-1-methyl-ethoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl) spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (45 mg, 0.079 mmol) prepared in Example 7 and CDI (26 mg, 0.16 mmol) in DMF (0.5 mL) was heated at 60° C. for 2 h. Then to this solution was added a mixture of cyclopropanesulfonamide (48 mg, 0.4 mmol) and NaH (13 mg, 60%, 0.3 mmol) in DMF (1 mL), which had been stirred at room temperature for 1 h. After the resulting mixture was stirred at room temperature for 1 h, it was poured into water (5 mL) and the aqueous solution was acidified to “pH” 2-3 by addition of concentrated aqueous hydrochloride acid. After the aqueous phase was extracted with EtOAc twice, the combined organic phases were dried over anhydrous Na2SO4, concentrated and the residue was purified by flash column to give the title compound as a white solid (38 mg).

1. additionThen to this solution was added
2. stirringAfter the resulting mixture was stirred at room temperature for 1 h
3. extractionAfter the aqueous phase was extracted with EtOAc twice
4. dry with materialthe combined organic phases were dried over anhydrous Na2SO4
5. concentrationconcentrated
6. customthe residue was purified by flash column