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

Participants

Reaction Conditions

Reaction Steps

1-(Phenylsulfonyl)-6-[1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1H-indazol-4-amine (663 mg, 1.252 mmol) in chloroform (10 mL) was stirred at 0° C. DIPEA (0.437 mL, 2.504 mmol) was added into the reaction mixture, then 2-(chloromethyl)-1,3-thiazole-4-carbonyl chloride (300 mg, 1.530 mmol) in chloroform (10.00 mL) was added. The reaction mixture was stirred at 0° C. for 15 mins. A further portion of 2-(chloromethyl)-1,3-thiazole-4-carbonyl chloride (400 mg, 1.252 mmol) was added to the reaction mixture and stirring was continued. When no further product formation was observed, further 2-(chloromethyl)-1,3-thiazole-4-carbonyl chloride (1.6 g, 1.252 mmol) was added to the reaction mixture which was stirred under nitrogen for 18 h. The solution was treated with DCM (25 mL) and saturated aqueous sodium bicarbonate (25 mL), then stirred for 10 mins. The organic layer was separated, washed with diluted aqueous sodium chloride (25 mL) and then passed through a hydrophobic frit. A part of the solvent was removed then the solution was applied to a silica column (Flasmaster II, 100 g silica cartridge) and eluted with a gradient of 0-100% ethylacetate/cyclohexane over 60 min. Fractions containing desired product we combined and the solvent was removed to afford the title compound as a white solid (111 mg).

Provenance & Evidence