Trifluoroacetic acid methylene chloride → HCID 118114781, compound

Participants

Reaction Steps

Crude (R)-tert-butyl 4-(4-(3-carbamoyl-6-(3-(3,3-dimethylureido)piperidin-1-yl)pyrazin-2-ylamino)-1H-pyrazol-1-yl)piperidine-1-carboxylate (277, 72 mg, 0.13 mmol) was treated with 2:1 DCM/TFA at RT for 1 hour and concentrated in vacuo to get (R)-5-(3-(3,3-dimethylureido)piperidin-1-yl)-3-(1-(piperidin-4-yl)-1H-pyrazol-4-ylamino)pyrazine-2-carboxamide (278) TFA salt. It was dissolved in 4 mL NMP. To it were added DIEA (230 μL, 1.3 mmol) and cyclopropanecarbobyl chloride (41 mg, 0.39 mmol). The mixture was stirred at RT for 2 hours, acidified with 0.5 mL TFA, and directly subjected to reverse phase prep HPLC using 5 mM HCl (aq) and neat MeCN as mobile phases to isolate (R)-3-(1-(1-(cyclopropanecarbonyl)piperidin-4-yl)-1H-pyrazol-4-ylamino)-5-(3-(3,3-dimethylureido)piperidin-1-yl)pyrazine-2-carboxamide (280) as HCl salt (32 mg, 47%). MS found for C25H36N10O3 as (M+H)+ 525.5, (M−H)− 523.3. UV: λ=253, 269, 298, 331, 374 nm.

Provenance & Evidence