反应详情

Cyclopropyl magnesium bromide (7.40 mL, 3.70 mmol, 0.5 M in diethyl ether) was added dropwise to a stirring solution of Example 85 (200 mg, 0.37 mmol) in THF (10 mL). This was allowed to stir until the reaction was complete by HPLC (1 hour). Additional amounts of the grinard reagent were added as needed. The reaction was quenched with methanol and was worked up by adding 1 volume of saturated NH4Cl solution and 5 volumes of EtOAc. The organic layer was washed 2× with NH4Cl and 1× with sodium carbonate soln. The organic layer was dried over Na2SO4 and concentrated. The crude intermediate was dissolved in DMSO (3 mL) and treated with Dess-Martin periodinane (174.7 mg, 0.412 mmol). The reaction was allowed to stir until the reaction was complete by HPLC (2 hours). The reaction was diluted with EtOAc (200 mL) and washed 2× with both saturated NaHCO3 and 2M sodium thiosulfate solution. The organic layer was dried over Na2SO4 and concentrated to give a crude solid which was purified by HPLC (10-70% ACN/H2O) to give 26.3 mg of the above compound (0.04 mmol, 12.3% yield). 1H-NMR (DMSO-d6). δ 9.98 (s, 1H), 9.82 (s, 1H), 8.60 (d, J=5.4 Hz, 1H), 8.11 (s, 1H), 8.03 (s, 1H), 7.69 (d, J=8.4 Hz, 2H), 0.745-7.41 (m, 3H), 4.08 (s, 2H), 3.55-3.52 (m, 4H), 2.46-2.43 (m, 4H), 2.07-1.97 (m, 1H), 0.95-0.91 (m, 2H), 0.74-0.69 (m, 2H). MS [M+H]+=581; LCMS RT=2.68 min.

1. customwas complete by HPLC (1 hour)
2. additionAdditional amounts of the grinard reagent were added
3. customThe reaction was quenched with methanol
4. additionby adding 1 volume of saturated NH4Cl solution and 5 volumes of EtOAc
5. washThe organic layer was washed 2× with NH4Cl and 1× with sodium carbonate soln
6. dry with materialThe organic layer was dried over Na2SO4
7. concentrationconcentrated
8. dissolutionThe crude intermediate was dissolved in DMSO (3 mL)
9. stirringto stir until the reaction
10. customwas complete by HPLC (2 hours)
11. washwashed 2× with both saturated NaHCO3 and 2M sodium thiosulfate solution
12. dry with materialThe organic layer was dried over Na2SO4
13. concentrationconcentrated
14. customto give a crude solid which
15. customwas purified by HPLC (10-70% ACN/H2O)