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 6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-amine (1.37 g, 3.53 mmol) in chloroform (30 ml) at 0° C. was added DIPEA (1.232 ml, 7.05 mmol). Crude 6-(chloromethyl)-2-pyridinecarbonyl chloride (1.519 g, crude) in chloroform (15 ml) was added dropwise and the mixture was stirred at 0° C. for 15 min. Water (30 ml) was added and the mixture was extracted with DCM (50 ml), separating the layers by hydrophobic frit. The solvent was removed in vacuo and the residue was dissolved in DCM (5 ml) and added to the top of 2×100 g silica SPE cartridges. One cartridge was eluted with 0-100% EtOAc/cyclohexane over 60 mins on the FlashMaster II. Product-containing fractions were and concentrated. The resultant solid was dissolved in 1:1 DCM/MeOH and loaded onto a 20 g aminopropyl cartridge that had been pre-conditioned with MeOH. The cartridge was then eluted with 1:1 DCM/MeOH and the fraction obtained was blown down under a stream of nitrogen. The solvent was removed in vacuo to give the title compound as a pink solid (487 mg). The second cartridge was eluted with 0-100% EtOAc/DCM over 60 mins on the FlashMaster II. The product-containing fractions were combined and concentrated to give a further portion of the title compound as a pink solid (449 mg).
