反应详情

5-amino-7-fluoro-1,3-dihydro-2H-indol-2-one from step 2 of this example (33 mg, 0.20 mmol) was slurried in DCE (0.9 ml) and acetic acid (51 uL, 0.89 mmol) and NaBH(OAc)3 (76 mg, 0.36 mmol) added. {(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}acetaldehyde (50 mg, 0.18 mmol) from Example 3 was added and the mixture stirred at RT for 2 hours. The mixture was diluted with EtOAc (30 ml), and partitioned across 4:1 water:saturated sodium bicarbonate (50 ml). The layers were separated, the aqueous phase extracted with EtOAc (2×30 ml), the organic fractions combined, dried over Na2SO4, filtered, and the volatiles removed in vacuum. The product was purified by chromatography on SiO2 eluting with 40% acetone:hexanes. This was followed by a second purification using chromatography on SiO2 eluting with 30% acetone:hexanes to give the titled compound. LRMS calc: 429.17; obs: 430.19 (M+1).

1. custompartitioned across 4:1 water
2. customThe layers were separated
3. extractionthe aqueous phase extracted with EtOAc (2×30 ml)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. customthe volatiles removed in vacuum
7. customThe product was purified by chromatography on SiO2 eluting with 40% acetone
8. customThis was followed by a second purification