Réaction #635864

Équation de réaction

Water

3-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide

N-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-2,3,4-trifluoro-N-methylbenzamide

potassium carbonate

→

required product

Rendement 3.1%

3-{[2-Fluoro-1-(fluoromethyl)ethyl]oxy}-5-[(9-fluoro-4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-N-(1-Methyl-1H-pyrazol-3-yl)benzamide

Rendement 3.1%

Solvants

DMA

Conditions de réaction

Traitement

1. 1
   Extractionthe solution extracted with ethyl acetate
2. 2
   LavageThe ethyl acetate layer was washed with brine (20 mL)
3. 3
   Séchagedried (MgSO4)
4. 4
   Autreevaporated to a residue which
5. 5
   workup.ADDITIONTFA (5 drops) added
6. 6
   AutreThe solvent was evaporated to a residue, which
7. 7
   Autrewas chromatographed by preparative HPLC on C18 reversed phase
8. 8
   Lavageeluting with 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA)

Mode opératoire

A solution of 3-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (100 mg, 0.32 mmol), N-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-2,3,4-trifluoro-N-methylbenzamide (112 mg, 0.32 mmol) and potassium carbonate (89 mg, 0.64 mmol) in DMA (2 mL) was heated in a microwave reactor for 2 hours. Water (20 mL) was added and the solution extracted with ethyl acetate. The ethyl acetate layer was washed with brine (20 mL), dried (MgSO4) and evaporated to a residue which was taken up in DCM (10 mL) and TFA (5 drops) added. The mixture was stirred at RT for 2 hours. The solvent was evaporated to a residue, which was chromatographed by preparative HPLC on C18 reversed phase, eluting with 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA), to give the required product (5 mg).

Source