反应详情

温度

70 °C

To a suspension of sodium hydride (0.030 g, 0.742 mmol) in THF (Ratio: 1.8, Volume: 2.272 ml) was added dropwise (Z)-(3-fluoro-4-(4-hydroxypyrimidin-5-yl)pyridin-2-yl)(4-fluorophenyl)methanone oxime (0.116 g, 0.353 mmol) in DMF (Ratio: 1.0, Volume: 1.262 ml) slowly. The reaction mixture was heated at 70° C. for 3.5 hr. Additional NaH (12 mg) was added. The reaction mixture was heated at 70° C. for 2.5 hr, and then allowed to cool to room temperature. The solvent was evaporated, and the mixture was further concentrated in vacuo to afford a brown residue. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed (required a few drops of MeOH). Purification of the crude material by silica gel chromatography using an ISCO machine (24 g column, 35 mL/min, 0-30% MeOH in CH2Cl2 over 25 min, tr=9 min) gave the title compound (53.4 mg, 0.173 mmol, 49.0% yield) as a yellow solid. ESI MS (M+H)+=309.1.

1. temperatureThe reaction mixture was heated at 70° C. for 2.5 hr
2. temperatureto cool to room temperature
3. customThe solvent was evaporated
4. concentrationthe mixture was further concentrated in vacuo
5. customto afford a brown residue
6. customto be chromatographed (required a few drops of MeOH)
7. customPurification of the crude material by silica gel chromatography
8. customan ISCO machine (24 g column, 35 mL/min, 0-30% MeOH in CH2Cl2 over 25 min, tr=9 min)