反应详情

Part C: A solution 3,5-dichloro-1-(1-ethylpropyl)-6-methyl-2(1H)-pyrazinone from Part B (80 mg, 0.321 mmol) and 7-chloro-5-methoxyindoline (61.9 mg, 0.337 mmol) in THF (1.6 mL) was cooled to 0° C. and was treated with sodium hexamethyldisilazide (353 μL, 0.353 mmol, 1 M in THF). The reaction mixture was allowed to warm up to room temperature and was stirred overnight. The mixture was transferred to a separatory funnel containing saturated NaHCO3 and the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (10% EtOAc in hexanes→40% EtOAc in hexanes) to provide the target compound (22 mg, 17% yield) as a brown oil: 1H NMR (CDCl3) δ 6.72 (s, 2 H), 4.27 (t, J=7.88 Hz, 2 H), 4.00-3.95 (m, 1 H), 3.77 (s, 3 H), 3.09 (t, J=7.8 Hz, 2H), 2.48-2.38 (m, 2 H), 2.42 (s, 3 H), 1.95-1.81 (m, 2 H), 0.87 (t, J=7.5 Hz, 6 H); HRMS (ESI) m/z 396.1259 [(M+H)+, calcd for C19H24N3O2Cl2 396.1246].

1. customThe mixture was transferred to a separatory funnel
2. extractionthe aqueous layer was extracted with EtOAc (3×20 mL)
3. washThe combined organic layers were washed with brine
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by column chromatography on silica gel (10% EtOAc in hexanes→40% EtOAc in hexanes)