Diisopropylethylamine → Tert-butyl(2r)-3-(4-chlorophenyl)-1-(4-(3-(2,3-dihydroxypropoxy)-1h-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-1-oxopropan-2-ylcarbamate

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, see Example 7), (R)-2-(tert-butoxycarbonylamino)-3-(4-chlorophenyl)propanoic acid (0.022 g, 0.074 mmol) and TBTU (0.0284 g, 0.0885 mmol) in DCM (1 mL) and stirred at room temperature for 1 hour. 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. Ether (20 mL) was then added. The organic layer was separated, washed with brine (10 mL), and dried over sodium sulfate. After removal of solvent, the resulting residue was purified by chromatography (ethyl acetate:MeOH, 20:1) to give tert-butyl(2R)-3-(4-chlorophenyl)-1-(4-(3-(2,3-dihydroxypropoxy)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-1-oxopropan-2-ylcarbamate 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 HCl in ether (1 mL, 2N) was added. The resulting solid was collected by filtration to give (2R)-2-amino-3-(4-chlorophenyl)-1-(4-(3-(2,3-dihydroxypropoxy)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)propan-1-one (0.010 g, 25%). MS APCI (+) m/z 475.2 detected.

Provenance & Evidence