Trifluoroacetic acid → 1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea

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Reaction Conditions

Reaction Steps

A mixture of 3-(2-methylpyridin-4-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-amine (intermediate 5a; 50 mg, 0.107 mmol) and 1-fluoro-4-[(1R)-1-isocyanatoethyl]-benzene (75 mg, 0.454 mmol) in 1,4-dioxane (1 mL) was heated to 60° C. overnight, then cooled down to RT and concentrated in vacuo. The residue was suspended in DCM and purified by chromatography on silica gel (0-50% MeOH/DCM) to yield a solid, which was directly dissolved in DCM (1 mL) and treated with TFA (1 mL). The mixture was stirred at RT for 3 h, then concentrated in vacuo and purified via reverse phase HPLC over a gradient of 20-55% MeCN with 0.1% TFA. The collected fractions were then partitioned between DCM/MeOH and 1N NaOH. The organic layer was dried (Na2SO4) and concentrated in vacuo to provide 1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea as a solid (13 mg, 0.033 mmol, 31%). MS ESI calc'd. for C21H20N6OF. [M+1]+ 391, found 391.

Provenance & Evidence