Réaction #48875

Équation de réaction

3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide

potassium carbonate

2-chloro-4,5-difluoro-N,N-dimethylbenzamide

→

title compound

Rendement 16.7%

2-Chloro-5-fluoro-4-(3-[(1S)-2-hydroxy-1-methylethoxy]-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenoxy)-N,N-dimethylbenzamide

Rendement 16.7%

Solvants

acetonitrile

Conditions de réaction

Traitement

1. 1
   AutreThe reaction mixture was quenched with water
2. 2
   Extractionextracted with DCM (2×6 mL)
3. 3
   SéchageThe organic layer was dried (MgSO4)
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated in vacuo
6. 6
   AutreThe residue was then chromatographed by preparatory reverse phase HPLC

Mode opératoire

A suspension of 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (200 mg, 0.477 mmol), potassium carbonate (136 mg, 0.95 mmol) and 2-chloro-4,5-difluoro-N,N-dimethylbenzamide (106 mg, 0.45 mmol) in acetonitrile (3.5 mL) was heated in a microwave reactor at 160° C. for 2 hours. The reaction mixture was quenched with water and extracted with DCM (2×6 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was then chromatographed by preparatory reverse phase HPLC using a gradient of 5-95% acetonitrile in water (containing 0.2% TFA) on a Phenomenex Luna 10u C18 (2) 100A (150×21.2 mm) column to give the title compound (37 mg).

Source