Morpholine → 4-({1,6-Diethyl-5-[({[4-(4-{[4-(4-morpholinyl)butyl]oxy}butyl)phenyl]carbonyl}amino)methyl]-1H-pyrazolo[3,4-b]pyridin-4-yl}amino)-1-piperidinecarboxamide

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Reaction Conditions

Reaction Steps

A mixture of 4-{[5-({[(4-{4-[(4-bromobutyl)oxy]butyl}phenyl)carbonyl]amino}methyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxamide (1.1 g, 1.67 mmol, e.g. which can be as prepared in Intermediate 28) in N,N-dimethylformamide (20 ml) was treated with N,N-diisopropylethylamine (0.567 ml) and morpholine (0.300 ml, 3.3 mmol) and heated at 65° C. The solvent was removed under vacuum and the residue was applied directly to a 100 g silica SPE cartridge and eluted with a gradient of from 0% to 50% methanol in dichloromethane over 40 mins. Fractions containing product were pooled and evaporated to give a pale orange foam which appeared to be about 85% pure by analytical HPLC. The residue was further purified by mass directed preparative HPLC (Method C, using 0.1% trifluoroacetic acid) in 50 mg portions, and, following evaporation of the solvent from the appropriate fractions, the residual material was dissolved in dichloromethane and washed with saturated aqueous sodium bicarbonate solution (NaHCO3). The organic fraction was collected by passing through a hydrophobic frit and evaporated to give the title compound (0.300 g) as a white foam. LCMS showed MH+=663; TRET=2.09 min.

Provenance & Evidence