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

Participants

Reaction Conditions

Reaction Steps

1-(Phenylsulfonyl)-6-[1-(phenylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-1H-indazol-4-amine (185 mg, 0.349 mmol) was dissolved in DCM (3 ml) and pyridine (0.034 mL, 0.418 mmol) was added. The mixture was cooled to 0° C. in an ice bath and 2-(chloromethyl)-1,3-thiazole-4-carbonyl chloride (77 mg, 0.349 mmol) in DCM (3 ml) was added dropwise over 5 mins. The mixture was stirred at 0° C. for 15 mins. A further portion of 2-(chloromethyl)-1,3-thiazole-4-carbonyl chloride (38.4 mg, 0.174 mmol) in DCM (1.5 ml) was added. The mixture was stirred for 2 hours, letting the ice melt over this time. A further portion of 2-(chloromethyl)-1,3-thiazole-4-carbonyl chloride (38.4 mg, 0.174 mmol) in DCM (1.5 ml) was added and stirring continued with monitoring by LCMS. The mixture was diluted with DCM (10 ml), saturated aqueous sodium bicarbonate (10 ml) was added and the mixture stirred vigorously for 10 mins. The organic layer was separated, washed with water (10 ml), passed through a hydrophobic frit and concentrated in vacuo. The residue was dissolved in DMSO and loaded onto a 43 g C18 Reverse Phase RediSep column that was then eluted with 30-85% acetonitrile (+0.1% TFA)/H2O (+0.1% TFA) over 30 mins. The product-containing fractions were combined and concentrated in vacuo to give a cream solid which was then dried on the vacuum line for 1 hour to give the title compound (54 mg).

Provenance & Evidence