Diisopropylethylamine → Tert-butyl(2s)-2-(4-chlorophenyl)-3-(4-(3-(2,3-dihydroxypropoxy)-1h-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate

Participants

Reaction Steps

DIEA (0.0514 mL, 0.295 mmol) was added to 3-(4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-3-yloxy)propane-1,2-diol dihydrochloride (0.030 g, 0.0737 mmol), (S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (0.0252 g, 0.0737 mmol, see Example B) and TBTU (0.0284 g, 0.0885 mmol) in DCM (1 mL) and stirred at room temperature for 2 hours. The reaction was concentrated to dryness. The resulting residue was dissolved in THF:MeOH (2 mL, 1:1), and a LiOH solution (1 mL, 2M) was added. The solution was stirred for 30 minutes, followed by the addition of ether (20 mL). The organic layer was separated, washed with brine (10 mL), and dried over sodium sulfate. After removal of the solvent, the resulting residue was purified by column chromatography (ethyl acetate:MeOH, 20:1) to give tert-butyl(2S)-2-(4-chlorophenyl)-3-(4-(3-(2,3-dihydroxypropoxy)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate as a solid. The solid was dissolved in DCM (1 mL), and TFA (0.4 mL) was added. The mixture was stirred at room temperature for 1 hour and then concentrated to dryness. The resulting residue was dissolved in DCM (0.5 mL), and 2N HCl in ether (1 mL) was added. The resulting solid was collected by filtration to give (2S)-2-(4-chlorophenyl)-1-(4-(3-(2,3-dihydroxypropoxy)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one dihydrochloride (0.014 g, 33%). MS APCI (+) m/z 517.2 detected.

Provenance & Evidence