Reaktion #163046

Reaktionsgleichung

H2O2

(R)-6-(5-Cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)-2-hydroxyethylamino)nicotinonitrile

KOH

→

title compound

Ausbeute 90.0%

(R)-6-(5-Cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)-2-hydroxyethylamino)nicotinamide

Ausbeute 90.0%

Lösungsmittel

MeOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooled to 25° C.
2. 2
   Einengenconcentrated
3. 3
   workup.DISSOLUTIONThe resulting residue was dissolved in EtOAc (50 ml)
4. 4
   Waschenwashed with water (30 ml)
5. 5
   Sonstigedried
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated
8. 8
   SonstigeThe resulting solid was purified by column chromatography (DCM-MeOH=30:1)

Vorschrift

(R)-6-(5-Cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)-2-hydroxyethylamino)nicotinonitrile (Example 6; 0.07 g, 0.2 mmol), was placed in MeOH (5 ml) at 25° C. A 25% aqueous solution (0.2 ml) of KOH (50 mg) was then added, followed by the addition of 0.05 ml of 30% H2O2. The resulting dark red solution was heated to 65° C. for 1 h, cooled to 25° C., and concentrated. The resulting residue was dissolved in EtOAc (50 ml), washed with water (30 ml), dried, filtered, and concentrated. The resulting solid was purified by column chromatography (DCM-MeOH=30:1) to give the title compound (0.065 g, 90%). 1H NMR (400 MHz, CD3OD) δ 7.69 (d, J=12.1 Hz, 1H), 7.39-7.36 (m, 2H), 7.04-7.00 (m, 2H), 5.94 (s, 1H), 5.22-5.16 (m, 1H), 3.87-3.75 (m, 2H), 1.91-1.84 (m, 1H), 0.98-0.96 (m, 2H), 0.74-0.69 (m, 2H). MS: Calcd.: 414. Found: [M+H]+ 415.

Quelle