Reaction #531884

Reaction equation

ethyl (2Z)-2-cyano-3-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]-3-{[1-(1,3-thiazol-2-yl)ethyl]amino}acrylate

ethylamine

AlMe3

→

(2Z)-2-cyano-N-cyclopropyl-3-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]-3-{[1-(1,3-thiazol-2-yl)ethyl]amino}acrylamide

Yield 54.2%

Solvents

toluene

Conditions

Workup

1. 1
   OtherThe reaction was quenched with aqueous saturated NH4Cl
2. 2
   Extractionextracted with ethylacetate
3. 3
   Dryingdried over MgSO4
4. 4
   Concentrationconcentrated under vacuum
5. 5
   OtherThe residue was purified by chromatography on silica gel

Procedure

A solution of ethyl (2Z)-2-cyano-3-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]-3-{[1-(1,3-thiazol-2-yl)ethyl]amino}acrylate (0.122 g, 0.32 mmol, 1 eq.) in 3 ml of toluene was treated with ethylamine (1 M solution in tetrahydrofurane, 0.96 ml, 0.96 mmol, 3 eq.) and AlMe3 (1 M solution in toluene, 0.96 ml, 0.96 mmol, 3 eq.). The reaction was microwaved at 110° C. for 1800s (fixed hold, high absorption). The reaction was quenched with aqueous saturated NH4Cl and extracted with ethylacetate. The organic layers were combined and dried over MgSO4 and concentrated under vacuum. The residue was purified by chromatography on silica gel to give (2Z)-2-cyano-N-cyclopropyl-3-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]-3-{[1-(1,3-thiazol-2-yl)ethyl]amino}acrylamide (0.068 g, 51% yield) as a mixture of atropoisomers.

Source