Diisopropylethylamine → HCID 68758743, compound

Participants

Reaction Steps

DIEA (0.0687 mL, 0.394 mmol) was added to a solution of 5-bromo-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridine dihydrochloride (0.050 g, 0.0986 mmol, see Example 11), (R)-2-(tert-butoxycarbonylamino)-3-(4-chlorophenyl)propanoic acid (0.0295 g, 0.099 mmol) and TBTU (0.0380 g, 0.118 mmol) in DCM (1 mL) and stirred at room temperature for 16 hours. The reaction was concentrated to dryness. The resulting residue was dissolved in THF/MeOH (2 mL, 1:1), and an aqueous LiOH solution (1 mL, 2M) was added. The solution was stirred for 30 minutes, and then ether (20 mL) was added. 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 (hexane:ethyl acetate, 1:1) to give (R)-tert-butyl 1-(4-(5-bromo-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-(4-chlorophenyl)-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 the reaction was 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 (R)-2-amino-1-(4-(5-bromo-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-(4-chlorophenyl)propan-1-one dihydrochloride (0.015 g, 29%). MS APCI (+) m/z 463.1 detected.

Provenance & Evidence