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

温度

-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)acrylic acid (0.2 g, 1.0 eq.) was charged along with dichloromethane (5 mL, 10V). The reaction mixture was cooled to −20° C. and then added pyrimidine-5-ylmethanamine (0.075 g, 1.2 eq), T3P (50% in EtOAc) (0.4 mL, 1.2 eq) followed by DIPEA (0.2 ml, 2 eq) dropwise into the reaction mixture. The reaction mixture was stirred at −20° C. for another 30 min. 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 concentrated by rotary evaporation (25° C., 20 mm Hg) to afford 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 collections (500 mL fractions). The compound started eluting from 4% methanol in dichloromethane. Fractions containing such TLC profile were collected together to obtain pure compound 0.2 g. Yield: 80%.

1. customIn a 50 mL, 3N round-bottomed flask equipped with nitrogen inlet
2. customReaction mixture
3. concentrationwas concentrated by rotary evaporation (25° C., 20 mm Hg)
4. customto afford crude compound
5. customThe crude reaction mixture
6. customwas purified by column chromatography
7. washstarted eluting in MeOH in gradient manner
8. washThe compound started eluting from 4% methanol in dichloromethane
9. additionFractions containing such TLC profile
10. customwere collected together

ORDレコード

ord-d8854004c5a64b359e52644be9f81b4c

出典データセット

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09428490B2