Reaktion #609305

Reaktionsgleichung

1-Amino-N-methylcyclopropanecarboxamide

5-(2,4-dichloro-5-(3-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylic acid

N,N-diisopropylethylamine

TPTU

→

title compound

Ausbeute 79.1%

5-{[2,4-dichloro-5-(3-fluoropyridin-2-yl)benzoyl]amino}-N-[1-(methylcarbamoyl)cyclopropyl]-1-phenyl-1H-pyrazole-3-carboxamide

Ausbeute 79.1%

Lösungsmittel

water

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe mixture stirred for 30 minutes
2. 2
   Extraktionextracted with EtOAc (3×20 mL)
3. 3
   WaschenThe combined organic layers were washed with saturated aqueous brine solution
4. 4
   Trocknendried (magnesium sulphate)
5. 5
   Einengenconcentrated in vacuo
6. 6
   SonstigeThe residue was purified by column chromatography over silica gel
7. 7
   Wascheneluting with EtOAc

Vorschrift

To a solution of 5-(2,4-dichloro-5-(3-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylic acid (Example 107, 961 mg, 2.04 mmol) in DMF (20 mL), were added N,N-diisopropylethylamine (0.8 mL, 5.5 mmol) and TPTU (848 mg, 2.85 mmol) and the mixture stirred at room temperature for 5 minutes. 1-Amino-N-methylcyclopropanecarboxamide (PCT Int. Appl., 2008051547) (300 mg, 2.65 mmol) was then added and the mixture stirred for 30 minutes. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were washed with saturated aqueous brine solution, dried (magnesium sulphate) and concentrated in vacuo. The residue was purified by column chromatography over silica gel, eluting with EtOAc to afford the title compound as a white solid (916 mg, 79%). Crystallisation by vapour diffusion using methanol as the solvent and acetonitrile as the anti-solvent also afforded the title compound as crystalline colourless needles.

Quelle