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0 °C

A 40 ml, vial was charged with a mixture of ethyl 3-methyl-1-((3-methylisoxazol-5-yl)methyl)-4-(6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazole-5-carboxylate and ethyl 5-methyl-1-((3-methylisoxazol-5-yl)methyl)-4-(6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazole-3-carboxylate (0.210 g) in THF (6 mL). The mixture was cooled to 0° C. A 1M solution of lithium aluminum hydride (1.454 mL, 1.454 mmol) in ether was added and the reaction mixture was stirred for 30 minutes at room temperature. The reaction was quenched with 1N HCl (2 mL) at 0° C. The mixture was allowed to warm to room temperature and the product was extracted into EtOAc. The organic phase was washed with brine and dried over Na2SO4. The volatiles were evaporated and the crude residue was purified by LCMS, eluting with 35% ACN in H2O (containing 10 mM NH4HCO3) over a period of 10 minutes. The product-containing fractions were combined and the volatiles evaporated using a GeneVac™ to give the title compounds. The later-eluting peak was assigned to the regioisomer of EXAMPLE 411 (3.3 mg). 1H NMR (400 MHz, CD3OD) δ ppm 2.19 (s, 3H), 2.30 (s, 3H), 4.59 (s, 2H), 5.63 (s, 2H), 6.26 (s, 1H), 7.31 (d, J=1.26 Hz, 1H), 7.92 (s, 1H), 8.04 (d, J=0.76 Hz, 1H); ESI-MS m/z [M+H]+ calc'd for C18H16F3N5O2, 392.13. found 392.21. The earlier-eluting peak was assigned to the regioisomer of EXAMPLE 412 (2.8 mg). 1H NMR (400 MHz, CD3OD) δ ppm 2.30 (s, 3H), 2.31 (s, 3H), 4.50 (s, 2H), 5.55 (s, 2H), 6.28 (s, 1H), 7.34-7.43 (m, 1H), 7.90 (s, 1H), 7.96-8.05 (m, 1H); ESI-MS m/z [M+H]+ calc'd for C18H16F3N5O2, 392.13. found 392.21.

1. customThe reaction was quenched with 1N HCl (2 mL) at 0° C
2. temperatureto warm to room temperature
3. extractionthe product was extracted into EtOAc
4. washThe organic phase was washed with brine
5. dry with materialdried over Na2SO4
6. customThe volatiles were evaporated
7. customthe crude residue was purified by LCMS
8. washeluting with 35% ACN in H2O (containing 10 mM NH4HCO3) over a period of 10 minutes
9. customthe volatiles evaporated