Methyl iodide → (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N-methyl-N-(pyrimidin-5-ylmethyl)acrylamide

Temperature

-20 °C

In a 50 mL, 3N round-bottomed flask equipped with nitrogen inlet, (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N-(pyrimidin-5-ylmethyl)acrylamide (0.05 g, 1.0 eq.) was charged along with THF (5 mL, 5V). The reaction mixture was cooled to −20° C. and sodium hydride (60% in mineral oil) was added (0.051 g, 1.1 eq.). Reaction mixture was allowed to stir for 1 h. Methyl Iodide (0.018 g, 1.1) was added into the reaction mixture and stirred at −20° C. for 1 h. The progress of the reaction was followed by TLC analysis on silica gel with 5% Methanol in dichloromethane as mobile phase and visualization with UV. Reaction mixture was quenched in water (50 mL) and extracted with EtOAc (50×2). The organic layer was washed with brine solution, dried over Na2SO4 and concentrated by rotary evaporation (25° C., 20 mm Hg) to afford 0.060 g of Crude compound. The crude reaction mixture was purified by column chromatography using 60/120 mesh silica and Methanol: dichloromethane as mobile phase. The column was packed in dichloromethane and started eluting in MeOH in gradient manner starting with fraction collection (500 mL fractions). The compound started eluting from 4% Methanol in dichloromethane. Fractions containing such TLC profile were collected together to obtain pure compound 0.015 g Yield (30%).

1. customIn a 50 mL, 3N round-bottomed flask equipped with nitrogen inlet
2. customReaction mixture
3. stirringstirred at −20° C. for 1 h
4. customReaction mixture
5. customwas quenched in water (50 mL)
6. extractionextracted with EtOAc (50×2)
7. washThe organic layer was washed with brine solution
8. dry with materialdried over Na2SO4
9. concentrationconcentrated by rotary evaporation (25° C., 20 mm Hg)
10. customto afford 0.060 g of Crude compound
11. customThe crude reaction mixture
12. customwas purified by column chromatography
13. washstarted eluting in MeOH in gradient manner
14. customstarting with fraction collection (500 mL fractions)
15. washThe compound started eluting from 4% Methanol in dichloromethane
16. additionFractions containing such TLC profile
17. customwere collected together

ORD record

ord-92e7e7f791b44a9fb4d6722d8e63c26b

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428490B2