反应详情

To a MeOH solution (5 ml) was added (S)-6-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)ethylamino)nicotinonitrile (Example 1; 0.15 g, 0.4 mmol), conc. HCl (0.1 ml), and Pd (10 wt. %, dry basis, on activated carbon, 0.12 g). The mixture was then flushed with N2, evacuated, and then placed under 40 psi of H2 for 6 hrs. The reaction was then evacuated, flushed with N2, filtered, washed with MeOH (3×30 ml), and concentrated. The resulting solid was dissolved in the mixture of DCM-MeOH (50:1, 100 ml), and a saturated aqueous solution of Na2CO3 (100 ml) was added, and the mixture was shaken vigorously for 30 min. The layers were then allowed to separate, and the aqueous layer was extracted with DCM (3×100 ml). The combined organic layers were dried, filtered and concentrated. The resulting solid was purified by column chromatography (DCM-MeOH=9:1) to give the title compound (0.09 g, 58%). 1H NMR (400 MHz, CD3OD) δ 7.42-7.38 (m, 2H), 7.15 (d, J=11. Hz, 1H), 7.02-6.97 (m, 2H), 5.15-5.08 (m, 1H), 3.74 (s, 2H), 1.88-1.81 (m, 1H), 1.54 (d, J=7.0 Hz, 3H), 0.93-0.92 (m, 2H), 0.67-0.63 (m, 2H). MS: Calcd.: 384. Found: [M+H]+ 385.

1. customThe mixture was then flushed with N2
2. customevacuated
3. customThe reaction was then evacuated
4. customflushed with N2
5. filtrationfiltered
6. washwashed with MeOH (3×30 ml)
7. concentrationconcentrated
8. dissolutionThe resulting solid was dissolved in the mixture of DCM-MeOH (50:1, 100 ml)
9. additiona saturated aqueous solution of Na2CO3 (100 ml) was added
10. customto separate
11. extractionthe aqueous layer was extracted with DCM (3×100 ml)
12. customThe combined organic layers were dried
13. filtrationfiltered
14. concentrationconcentrated
15. customThe resulting solid was purified by column chromatography (DCM-MeOH=9:1)