Hydrochloric Acid → (S)-2-(4-chloro-5-fluoroindolin-1-yl)-4-hydroxy-N-(5-(N-thiazol-2-ylsulfamoyl)pyridine-2-yl)butanamide

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Reaction Steps

Prepared using General Procedure 2. To a stirring suspension of the 6-amino-N-(thiazol-2-yl)pyridine-3-sulfonamide (92 mg, 0.36 mmol) and DCE (2.0 mL) under N2, at RT, was added 2 M trimethylaluminum in hexanes (0.18 mL, 0.36 mmol) dropwise over 5 minutes. The solution was stirred at ambient temperature for 30 minutes. To this solution was added, a solution of (S)-3-(4-chloro-5-fluoroindolin-1-yl)dihydrofuran-2(3H)-one (92 mg, 0.36 mmol) in DCE (1.0 mL) over 5 minutes. The solution was stirred at 70° C. for 19 hours. The solution was cooled to 0° C. and aqueous 1.0 M HCl was added dropwise. The organic portion was washed with 1.0 N aqueous HCl (2×5.0 mL) and evaporated to dryness under reduced pressure. The residue was purified via silica gel chromatography using 5%-10% MeOH in CH2Cl2 to obtain (S)-2-(4-chloro-5-fluoroindolin-1-yl)-4-hydroxy-N-(5-(N-thiazol-2-ylsulfamoyl)pyridine-2-yl)butanamide (47 mg, 26%) as a yellow solid.

Provenance & Evidence