Reaktion #163096

Reaktionsgleichung

n-butanol

6-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-2,5-difluoronicotinonitrile

N-[5-(1-aminoethyl)-2-fluorophenyl]acetamide

(S)-3-Fluoro-N6-(1-(4-fluorophenyl)ethyl)-N2-(5-isopropoxy-1H-pyrazol-3-yl)-5-nitropyridine-2,6-diamine

DIEA

→

title compound

N-{5-[1-({3-Cyano-6-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-5-fluoropyridin-2-yl}amino)ethyl]-2-fluorophenyl}acetamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONTo a 10-ml microwave reaction vessel was added
2. 2
   EinengenThe reaction was concentrated in vacuo
3. 3
   Sonstigepurified by silica gel chromatography (Biotage Horizon System)
4. 4
   Waschena gradient elution of 25-35% EtOAc (20% v/v MeOH) in hexanes
5. 5
   Sonstigeto give

Vorschrift

To a 10-ml microwave reaction vessel was added, 6-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-2,5-difluoronicotinonitrile (Method 32, 300 mg, 1.13 mmol), N-[5-(1-aminoethyl)-2-fluorophenyl]acetamide (Method 66, 331 mg, 1.7 mmol), and DIEA (0.8 ml, 4.6 mmol) in n-butanol (4 ml). The resulting suspension was set to microwave heating (CEM Discover System) at 150° C. for 3 hours. The reaction was concentrated in vacuo and purified by silica gel chromatography (Biotage Horizon System) using a gradient elution of 25-35% EtOAc (20% v/v MeOH) in hexanes to give 180 mg (36% isolated yield) of the title compound. 1H NMR: 9.66 (br s, 1H) 9.43 (s, 1H) 7.81 (d, J=6.03 Hz, 2H) 7.60 (d, J=11.30 Hz, 1H) 6.92-7.21 (m, 3H) 5.98 (s, 1H) 5.13 (t, J=7.16 Hz, 1H) 2.05 (s, 3H) 1.76-1.92 (m, 1H) 1.46 (d, J=6.78 Hz, 3H) 0.82-0.95 (m, J=8.29 Hz, 2H) 0.54-0.66 (m, 2H). MS: Calcd.: 437. Found: [M+H]+ 438.

Quelle