2-Amino-5-bromo-N,N-dimethylbenzamide → 2,2-Dimethyl-propionic acid 5-(4-amino-3-dimethylcarbamoyl-phenyl)-3-(2-methoxy-phenyl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 2,2-dimethyl-propionic acid 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3]dioxolan-2-yl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester (6.5 g, 14 mmol), 2-amino-5-bromo-N,N-dimethyl-benzamide (3.4 g, 14 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]-palladium(II) dichloromethane adduct (511 mg, 0.7 mmol) in THF/Acetonitrile/saturated NaHCO3 (25 ml/25 ml/30 ml) was stirred at 100° C. for 4 hours. The mixture was allowed to cool down to room temperature and then extracted with ethyl acetate (3×). The combined organic layers were extracted with brine, dried with Na2SO4, decanted, and concentrated to dryness. Silica chromatography of the crude using a gradient of ethyl acetate and hexane afforded 2,2-dimethyl-propionic acid 5-(4-amino-3-dimethylcarbamoyl-phenyl)-3-(2-methoxy-phenyl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester (3.7 g, 52% yield).

Provenance & Evidence