Hydrochloric Acid → HCID 178458646, 화합물

The mixture of (S)-5-fluoro-2-(1-(4-fluorophenyl)ethylamino)-6-(5-isopropoxy-1H-pyrazol -3-ylamino)nicotinonitrile (Example 16; 0.90 g, 2.26 mmol), conc. HCl (0.3 ml), and Pd (10 wt. %, dry basis, on activated carbon, 0.55 g) in MeOH (20 ml) was flushed with N2, evacuated, and then placed under H2 (40 psi) 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 treated with a saturated aqueous Na2CO3 solution (100 ml). The mixture was shaken vigorously for 30 min and allowed to separate. 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 reverse-phase column chromatography (5-50% CH3CN in H2O over 400 ml) to give the title compound (0.7 g, 77%). 1H NMR (400 MHz, CD3OD) δ 7.45-7.41 (m, 2H), 7.35 (d, J=10.9 Hz, 1H), 7.03-6.99 (m, 2H), 5.35 (s, 1H), 5.09-5.04 (m, 1H), 4.55-4.49 (m, 1H), 4.18 (d, J=14.2 Hz, 1H), 4.08 (d, J=14.2 Hz, 1H), 1.59 (d, J=6.8 Hz, 3H), 1.31 (d, J=8.3 Hz, 6H). MS: Calcd.: 402. Found: [M+H]+ 403.

1. customwas 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. additiontreated with a saturated aqueous Na2CO3 solution (100 ml)
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 reverse-phase column chromatography (5-50% CH3CN in H2O over 400 ml)

ORD 기록

ord-bf48137e2112409fb23ee4a5783e1443

출처 데이터셋

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08324252B2