Aluminium lithium hydride → (3-methyl-1-((1-methyl-1H-pyrazol-4-yl)methyl)-4-(6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazol-5-yl)methanol

Participants

Reaction Conditions

Reaction Steps

A 100 mL round bottom flask was charged with ethyl 3-methyl-1-((1-methyl-1H-pyrazol-4-yl)methyl)-4-(1-(tetrahydro-2H-pyran-2-yl)-6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazole-5-carboxylate (0.745 g, 1.442 mmol) in THF (10 mL). The mixture was cooled to 0° C. A 1M solution of lithium aluminum hydride (4.33 mL, 4.33 mmol) in ether was added, and the reaction mixture was stirred at 0° C. for 1 hour. The reaction was quenched with 1N HCl (6 mL) at 0° C. and the product was extracted into EtOAc. The organic phase was washed with brine and dried over Na2SO4. The volatiles were removed by evaporation. The crude residue was dissolved in MeOH (5 mL). HCl (0.5 mL) was added and the mixture was stirred for 2 hours. The product was purified by LCMS, eluting with 30% ACN in H2O (containing 10 mM NH4HCO3) over a period of 10 minutes. The product-containing fractions were combined and the volatiles were evaporated using a GeneVac™ to give the title compound (0.178 g, 31.6%). 1H NMR (400 MHz, CD3OD) δ ppm 2.27 (s, 3H), 3.88 (s, 3H), 4.51 (s, 2H), 5.30 (s, 2H), 7.37 (d, J=1.26 Hz, 1H), 7.52 (s, 1H), 7.65 (s, 1H), 7.88 (s, 1H), 7.94-8.02 (m, 1H); ESI-MS m/z [M+H]+ calc'd for C18H17F3N6O, 391.15. found 391.13.

Provenance & Evidence