Lithium Hydroxide → 1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-carboxylic acid

Methyl 1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-carboxylate (Intermediate 204, 0.312 g, 1.5 mmol) was dissolved in a mixture of THF (2 mL), MeOH (2 mL) and water (1 mL); lithium hydroxide (0.188 g, 4.5 mmol) was added and the mixture was stirred at room temperature for 16 h. The mixture was concentrated, the residue dissolved in water (1 mL) and the mixture was neutralised. This was extracted with EtOAc (2×10 mL), the organic extracts were dried over sodium sulfate and concentrated under vacuum. The crude material was washed with pentane (2×10 mL) to afford 1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-carboxylic acid (0.200 g, 69%). 2-N-methyl-2-N-phenyl-6-{5-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl]-1,2,4-oxadiazol-3-yl}-1,3,5-triazine-2,4-diamine was then prepared from 1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-carboxylic acid (0.159 g, 0.820 mmol) and 4-amino-N-hydroxy-6-[methyl(phenyl)amino]-1,3,5-triazine-2-carboximidamide (prepared in an analogous manner to Intermediate 1, 0.125 g, 0.483 mmol) according to the method described for Example 251 to afford the title compound (0.110 g, 55%).

1. concentrationThe mixture was concentrated
2. dissolutionthe residue dissolved in water (1 mL)
3. extractionThis was extracted with EtOAc (2×10 mL)
4. dry with materialthe organic extracts were dried over sodium sulfate
5. concentrationconcentrated under vacuum
6. washThe crude material was washed with pentane (2×10 mL)

ORD record

ord-5016fb777ce4461b87cfb27c7c9f4b4c

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895733B2