Sodium Iodide → HCID 20740255, compound

Participants

Reaction Steps

To 150 mg (0.36 mmol) of 6-Chloro-1-(3-hydroxy-propyl)-1H-indole-2-carboxylic acid [(1S,2R)-2-(cyanomethyl-carbamoyl)-cyclohexyl]-amide (from Example 45) dissolved in 5 mL DMF was added 151 mg (0.58 mmol) triphenylphosphine. At 0° C., N-bromosuccinimide (104 mg, 0.58 mmol) was added in portions. After stirring at room temperature for 30 minutes, sodium methane sulfinate (88 mg, 0.73 mmol) and sodium iodide (6 mg, 0.036 mmol) were added in portions. The reaction mixture was then stirred at 70° C. for 3 hours, cooled to room temperature, partitioned between ethyl acetate and 5% aqueous sodium thiosulfate solution, washed with water, dried over magnesium sulfate, and concentrated. Column chromatography, eluting with 70% ethyl acetate in hexane, followed by recrystallization from ether provided 50 mg of 6-chloro-1-(3-methanesulfonyl-propyl)-1H-indole-2-carboxylic acid [(1S,2R)-2-(cyanomethyl-carbamoyl)-cyclohexyl]-amide. HPLC: 87% pure, yield: 30%, MS: 479 (M H+).

Provenance & Evidence