Hydrochloric Acid → 4-{[5-(Azidomethyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxamide

Participants

Reaction Steps

A solution of 1,1-dimethylethyl 4-{[5-(azidomethyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxylate (8.9 g, 20.8 mmol, e.g. which can be as prepared in Intermediate 15) in 1,4-dioxane (50 ml) was treated with 4M HCl in 1,4-dioxane (125 ml). After 2 hours the solvent was evaporated and the residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The organic phase was collected and washed with saturated aqueous sodium bicarbonate solution. The combined aqueous phases were back-extracted with dichloromethane. The combined organic phases were dried (Na2SO4) and the solvent was evaporated to give an oil (LCMS showed MH+=329; TRET=1.75 min). The oil was dissolved in dichloromethane (100 ml), and the solution was treated with N,N-diisopropylethylamine (6.1 ml, 35.0 mmol) followed by trimethylsilyl isocyanate (3.6 ml, 26.6 mmol, commercially available e.g. trimethylsilyl isocyanate 85% from Aldrich). The reaction mixture was stirred at room temperature overnight. Additional N,N-diisopropylethylamine (6.1 ml, 35.0 mmol) and trimethylsilyl isocyanate (3.6 ml, 26.6 mmol) was added. After stirring for a further 7 hours, additional trimethylsilyl isocyanate (3.6 ml) was added and stirring was continued over the weekend (e.g. this can be about 62 hours). Water (100 ml) was added and the mixture was stirred for 1 hour. The precipitated solid was collected by filtration, washed with water followed by diethyl ether, and then dried to give the title compound (2.21 g). LCMS m/z 372 [MH+]; TRET=2.08 min.

Provenance & Evidence