Reaction #156297

Reaction equation

N-{4-bromo-2-[(2E)-3-(dimethylamino)prop-2-enoyl]-5-(trifluoromethyl)phenyl}-2,2,2-trifluoroacetamide

tetrahydro-2H-pyran-4-ylhydrazine dihydrochloride

N-methylpyrrolidone

DIPEA

→

N-{4-bromo-2-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-5-yl]-5-(trifluoromethyl)phenyl}-2,2,2-trifluoroacetamide

Yield 42.1%

Solvents

water

Conditions

Workup

1. 1
   workup.STIRRINGby stirring at 110° C. for 1 hour
2. 2
   Extractionfollowed by extraction with isopropyl acetate
3. 3
   Washthe organic layer was washed with saturated brine
4. 4
   OtherThe solvent was evaporated under reduced pressure
5. 5
   Otherthe residue was purified by silica gel column chromatography (chloroform/methanol)
6. 6
   OtherThe obtained oil was triturated with diethyl ether/n-hexane

Procedure

To a mixture of 6.0 g of tetrahydro-2H-pyran-4-ylhydrazine dihydrochloride and 175 mL of N-methylpyrrolidone was added 11 mL of DIPEA, followed by stirring at room temperature for 20 minutes. To the reaction mixture was added 8.86 g of N-{4-bromo-2-[(2E)-3-(dimethylamino)prop-2-enoyl]-5-(trifluoromethyl)phenyl}-2,2,2-trifluoroacetamide, followed by stirring at 110° C. for 1 hour. To the reaction mixture was added water, followed by extraction with isopropyl acetate, and the organic layer was washed with saturated brine. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (chloroform/methanol). The obtained oil was triturated with diethyl ether/n-hexane to obtain 4.19 g of N-{4-bromo-2-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-5-yl]-5-(trifluoromethyl)phenyl}-2,2,2-trifluoroacetamide.

Source