Sodium hydride → N-[2-(3-{2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}pyrrolo[2,3-b]pyridin-1-yl)acetyl]methanesulfonamide

Participants

Reaction Steps

To a solution of 107 mg (0.22 mmol) of (3-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}pyrrolo[2,3-b]pyridin-1-yl)acetic acid in 3 mL of DMF was added 108 mg (0.66 mmol) of N,N-carbonyldiimidazole. The mixture stirred for 5 minutes and then 63 mg (0.66 mmol) of methanesulfonamide was added. After 30 minutes, the reaction was monitored by LCMS indicating only starting material [MS m/z 485.29 (MH+)]. To the mixture was added sodium hydride and the mixture stirred for 1.5 hours. The mixture was monitored by LCMS indicating desired product [MS m/z 562.37 (MH+)]. TLC (ethyl acetate or methanol-dichloromethane) indicated a new product. The mixture was diluted with saturated aqueous ammonium chloride and extracted with five 10 mL portions of ethyl acetate. The combined organic layers were washed with two 7 mL portions of saturated aqueous ammonium chloride, two 7 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The oily residue was chromatographed on silica gel using dichloromethane to load the sample and then methanol-dichloromethane (1-10%) to afford some mixed factions and clean fractions. Fractions containing product were chromatographed on four prep. plate (1 mm, methanol-dichloromethane 15:85). The most polar band was recovered eluting from the silica gel with 20% methanol-dichloromethane. The material was triturated with ether-hexanes to afford 42 mg (33%) of the title compound as a tan solid. MS m/z 562.39 (MH+).

Provenance & Evidence