Reaktion #163093

Reaktionsgleichung

2,5-difluoro-6-(5-isopropoxy-1H-pyrazol-3-ylamino)nicotinonitrile

DIEA

(S)-1-(5-fluoropyridin-2-yl)ethanamine

→

title compound

Ausbeute 58.5%

(S)-5-Fluoro-2-(1-(5-fluoropyridin-2-yl)ethylamino)-6-(5-isopropoxy-1H-pyrazol-3-ylamino)nicotinonitrile

Ausbeute 58.5%

Lösungsmittel

n-BuOH

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Extraktionextracted with DCM (2×50 ml)
2. 2
   TrocknenThe combined organic fractions were dried over Na2SO4
3. 3
   Filtrationfiltered
4. 4
   Einengenconcentrated
5. 5
   SonstigeThe resulting oil was purified by column chromatography (hexanes-EtOAc=3:1)

Vorschrift

A solution of 2,5-difluoro-6-(5-isopropoxy-1H-pyrazol-3-ylamino)nicotinonitrile (Method 42, 0.30 g, 1.07 mmol), DIEA (0.16 g, 1.29 mmol), and (S)-1-(5-fluoropyridin-2-yl)ethanamine (Method 33; 0.22 g, 1.6 mmol) in n-BuOH (3 ml) was heated to 130° C. for 18 hours. The reaction was then cooled to room temperature, diluted with water (20 ml), and extracted with DCM (2×50 ml). The combined organic fractions were dried over Na2SO4, filtered, and then concentrated. The resulting oil was purified by column chromatography (hexanes-EtOAc=3:1) to give the title compound (0.25 g, 58%). 1H NMR (400 MHz, CD3OD) δ 8.40 (s, 1H), 7.56-7.55 (m, 2H), 7.45 (d, J=10.5 Hz, 1H), 5.42 (s, 1H), 5.25-5.22 (m, 1H), 4.63 (br s, 1H), 1.60 (d, J=7.0 Hz, 3H), 1.34 (d, J=6.1 Hz, 6H). MS: Calcd.: 399. Found: [M+H]+ 400.

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