Acetone, oxime → HCID 12096249, compound

Participants

Reaction Steps

To a solution of acetone oxime (74 mg, 1.0 mmol) in DMF (6 mL) was added sodium t-butoxide (1 M in THF, 1.0 mL). The mixture was stirred at room temperature for half hour followed by addition of a solution of 1,1-dimethylethyl 7-[4-[[[1-[4-fluoro-3-cyanophenyl]-3-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl]amino]phenyl]-1,2-benzisothiazole-2(3H)-carboxylate 1,1-dioxide (0.22 g, 0.34 mmol) prepared according to Example 15 in DMF (4 mL). The reaction was stirred at room temperature for 5 hours. The reaction mixture was then partitioned between ethyl acetate and HCl (5%), washed with HCl (5%), four times with water, brine, dried over sodium sulfate, filtered and concentrated. Flash chromatography (30% ethyl acetate/hexane) gave 100 mg of 1,1-dimethylethyl 7-[4-[[[1-[4-isopropylideneaminooxy-3-cyanophenyl]-3-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl]amino]phenyl]-1,2-benzisothiazole-2(3H)-carboxylate 1,1-dioxide. The intermediate (100 mg, 0.14 mmol) was dissolved in ethanol (4 mL) and to the solution was added HCl (20%, 4 mL). The reaction mixture was stirred at 80° C. for three hours. The reaction mixture was cooled to room temperature. The white precipitate was filtered to give the product that was purified by HPLC utilizing gradient elution with a mixture of water: acetonitrile with 0.05% of trifluoroacetic acid on a reverse phase C18 (60 angstrom) column to give the title compound (37 mg, 19%). LRMS (ES+) 577.1 (M+Na)+.

Provenance & Evidence