反应详情

2-[(Phenylmethyl)oxy]-N-3-pyridinyl-5-{[(2S)-2-pyrrolidinylmethyl]oxy}benzamide (may be prepared as described in Example 46; 80 mg, 0.20 mmol) was added to formic acid (4 ml) at 5° C., followed by aqueous formaldehyde (40%, 2.0 ml). When the initial evolution of carbon dioxide had subsided, the mixture was refluxed for 2 h. After the solution was cooled, the pH of the solution was adjusted to 7-8 by adding aqueous NaHCO3 solution. The mixture was extracted with dichloromethane. The organic layer was dried over Na2SO4, and concentrated to obtain a crude product. The crude product was purified by prep-HPLC (Gilson GX-281, waters X-Bridge 5 μm, 100*19 mm; A: 0.04% NH3.H2O/water, B: CH3CN; 0-7.2 min, 40%-50%; 7.2-7.5 min, 50%-95%; 7.5-11.5 min, 95%, RT=4.0 min) to yield the title compound as a white solid. 68 mg.

1. temperaturethe mixture was refluxed for 2 h
2. temperatureAfter the solution was cooled
3. extractionThe mixture was extracted with dichloromethane
4. dry with materialThe organic layer was dried over Na2SO4
5. concentrationconcentrated
6. customto obtain a crude product
7. customThe crude product was purified by prep-HPLC (Gilson GX-281, waters X-Bridge 5 μm, 100*19 mm
8. custom0-7.2 min, 40%-50%
9. custom7.2-7.5 min, 50%-95%