Water → 6-(Chloromethyl)-N-{1-(phenylsulfonyl)-6-[1-(phenylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-1H-indazol-4-yl}-2-pyridinecarboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-(hydroxymethyl)-2-pyridinecarboxylic acid (500 mg, 3.27 mmol) in chloroform (10 ml) and N,N-dimethylformamide (DMF) (0.1 ml) was added thionyl chloride (1 ml, 13.70 mmol) and the mixture heated at 65° C. for 1 hr. Solvent was removed in vacuo and the residue was azeotroped with chloroform (5 ml) then dried on a high vacuum line for 30 mins to afford an orange oil (650 mg), presumed to be 6-(chloromethyl)-2-pyridinecarbonyl chloride. To solution of 1-(phenylsulfonyl)-6-[1-(phenylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-1H-indazol-4-amine (581 mg, 1.095 mmol) in chloroform (5 ml) at 0° C. was added DIPEA (0.383 ml, 2.190 mmol). 6-(chloromethyl)-2-pyridinecarbonyl chloride (330 mg, 1.737 mmol) in chloroform (5 ml) was added dropwise and the mixture was stirred at 0° C. for 15 min then allowed to warm to room temperature and stirred for another 30 mins. Water (10 ml) was added to quench the reaction and the mixture was extracted with DCM (2×20 ml), separating the layers using a hydrophobic frit. The solvent was removed in vacuo to give a brown solid, which was triturated with ether (5 ml). The resultant cream solid was filtered off and dried in a vacuum oven for 30 mins to afford the title compound (658 mg).

Provenance & Evidence