反应详情

Sodium hydride (0.242 g, 6.06 mmol) was added portionwise to a solution of (6S)-3-iodo-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (described in Intermediate 4) (2.00 g, 5.51 mmol) in DMF (50 mL) at 0° C. After stirring for 10 min, 2-(trimethylsilyl)ethoxymethyl chloride (1.01 g, 6.06 mmol) was added dropwise. The resulting mixture was warmed slowly to ambient temperature and stirred for 48 h. The reaction was partitioned between water (20 mL) and EtOAc (100 mL). The organic layer was removed and the aqueous phase was extracted further with EtOAc (30 mL). The combined organic extracts were washed with brine, then dried over sodium sulfate, filtered, and concentrated to dryness in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexanes:EtOAc—95:5 to 50:50, to give the title compound. MS: m/z=493.9 (M+1).

1. stirringstirred for 48 h
2. customThe reaction was partitioned between water (20 mL) and EtOAc (100 mL)
3. customThe organic layer was removed
4. extractionthe aqueous phase was extracted further with EtOAc (30 mL)
5. washThe combined organic extracts were washed with brine
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated to dryness in vacuo
9. customThe crude product was purified by silica gel chromatography
10. washeluting with a gradient of hexanes