158580-55-3

2-Chloro-4-[(methylsulfonyl)Amino]benzoic Acid Methyl Ester is used as a reactant in the synthesis of second generation pyridyl biphenyl amide inhibitors of hedgehog pathway.

General procedure for the synthesis of methyl 2-chloro-4-(methylsulfonylamino)benzoate from methyl 2-chloro-4-aminobenzoate and methanesulfonyl chloride: pyridine (2 mL) was added to a stirred dichloromethane solution of methyl 2-chloro-4-aminobenzoate (0.457 g, 2.45 mmol) that was cooled to 0°C, followed by slow dropwise addition of methanesulfonyl chloride (0.2 mL, 2.5 mmol). After the dropwise addition, the reaction mixture was gradually warmed up to room temperature and stirred continuously for 2 hours. After completion of the reaction, the mixture was concentrated under vacuum. To the concentrated residue was added 1N hydrochloric acid (5 mL) and the mixture was extracted with ethyl acetate (10 mL). The organic phase was dried with anhydrous sodium sulfate and concentrated under high vacuum. The crude product was purified by column chromatography to afford the target product methyl 2-chloro-4-(methylsulfonylamino)benzoate as a solid (0.54 g, 84% yield).

[1] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 22, p. 6748 - 6753
[2] Patent: WO2010/65760, 2010, A1. Location in patent: Page/Page column 150-151
[3] Patent: WO2009/126863, 2009, A2. Location in patent: Page/Page column 164-165
[4] Patent: US2006/63779, 2006, A1. Location in patent: Page/Page column 112