Diisopropylethylamine → (S)-5-Amino-1-(4-fluorophenyl)-N-[3,3,3-trifluoro-2-hydroxy-2-(hydroxymethyl)propyl]-1H-pyrazole-4-carboxamide

5-Amino-1-(4-fluorophenyl)-1H-pyrazole-4-carboxylic acid (104 mg) was dissolved in dry dimethylformamide (3 ml) and diisopropylethylamine (0.33 ml) was added followed by the addition of O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyl uronium hexafluorophosphate (196 mg). The reaction was stirred at room temperature, under nitrogen, for 20 minutes. (S)-2-(Aminomethyl)-3,3,3-trifluoro-1,2-propanediol (90 mg) in dry dimethylformamide (2 ml) was added and the reaction was stirred at room temperature for 3 hours. The reaction was partitioned between ethyl acetate (50 ml) and water (50 ml) and the separated aqueous phase was re-extracted with ethyl acetate (50 ml). The combined organics were washed with water, 1M hydrochloric acid, 10% lithium chloride solution (2 times), bicarbonate and brine. The organics were dried using a hydrophobic frit and evaporated to give a pale yellow oil (200 mg). This was dissolved in dichloromethane (ca. 5 ml) and left to stand at room temperature for 4 hours wherein a precipitate formed. The precipitate was filtered and washed with a small amount of dichloromethane to give the title compound as a white solid (93 mg).

1. stirringthe reaction was stirred at room temperature for 3 hours
2. customThe reaction was partitioned between ethyl acetate (50 ml) and water (50 ml)
3. extractionthe separated aqueous phase was re-extracted with ethyl acetate (50 ml)
4. washThe combined organics were washed with water, 1M hydrochloric acid, 10% lithium chloride solution (2 times), bicarbonate and brine
5. customThe organics were dried
6. customevaporated

ORD record

ord-dd88024411c0429ba826ad8cf72b1391

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08247377B2