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, followed by 2-(chloromethyl)-1,3-thiazole-4-carbonyl chloride (300 mg, 1.530 mmol) in chloroform (10 mL). 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 and the reaction was monitored by LCMS. When no further conversion was apparent, a further portion of 2-(chloromethyl)-1,3-thiazole-4-carbonyl chloride (1.6 g, 1.252 mmol) was added and the reaction mixture was stirred for 18 h. The solution was treated with DCM (25 mL) and saturated aqueous sodium bicarbonate (25 mL) and stirred for 10 mins. The organic layer was separated, washed with aqueous sodium chloride (25 mL) and then passed through a hydrophobic frit. The residual solvent volume was reduced and the mixture was purified by silica column chromatography (Flashmaster II, 100 g cartridge) using a gradient of 0-100% ethylacetate/cyclohexane over 60 min to afford the title compound as a white solid (111 mg).

Provenance & Evidence