反应详情

The title compound is prepared by essentially following the procedure as described in Example 1 using (3R,4R)-4-(tert-butyl(dimethyl)silyl)oxytetrahydrofuran-3-amine (Preparation 36) and 2-chloro-4-fluoro-3-methyl-benzonitrile. The crude product is purified on silica gel using 40-70% EtOAc/hexanes. The isolated product is dissolved in THF to make a 0.5 M solution. TBAF (2.0 mL, 2 mmol, 1 M solution in THF) is added and stirred at room temperature for 16 h. The solution is concentrated in vacuo, EtOAc is added, and the solution is washed with water (2×). The organic portion is dried over magnesium sulfate, filtered, and concentrated. The residue is purified by reverse phase chromatography on silica-bound C18 using 15-95% acetonitrile/water+0.1% formic acid. Fractions containing the title compound are concentrated in vacuo to remove acetonitrile, then extracted with EtOAc. The organics are dried over magnesium sulfate and concentrated in vacuo to give the title compound as a white solid (134 mg, 19%). 1H-NMR (400 MHz, DMSO-d6) δ 7.53 (d, J=8.7 Hz, 1H), 6.73 (d, J=8.8 Hz, 1H), 5.60-5.56 (m, 1H), 5.53 (d, J=4.9 Hz, 1H), 4.33-4.29 (m, 1H), 4.05-3.99 (m, 2H), 3.92 (dd, J=4.6, 9.6 Hz, 1H), 3.63 (dd, J=2.4, 9.5 Hz, 1H), 3.53-3.50 (m, 1H), 2.19 (s, 3H). LC-ES/MS m/z 253 (M+1).

1. customThe title compound is prepared
2. customThe crude product is purified on silica gel using 40-70% EtOAc/hexanes
3. dissolutionThe isolated product is dissolved in THF
4. concentrationThe solution is concentrated in vacuo, EtOAc
5. additionis added
6. washthe solution is washed with water (2×)
7. dry with materialThe organic portion is dried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue is purified by reverse phase chromatography on silica-bound
11. additionFractions containing the title compound
12. concentrationare concentrated in vacuo
13. customto remove acetonitrile
14. extractionextracted with EtOAc
15. dry with materialThe organics are dried over magnesium sulfate
16. concentrationconcentrated in vacuo