Acetic Anhydride → n-(4-Hydroxy-1-(3-methylbutyl)-3-{7-[(methylsulfonyl)amino]-1,1-dioxido-4h-1,2,4-benzothiadiazin-3-yl}-2-oxo-1,2-dihydronaphthalen-1-yl)acetamide

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Reaction Steps

To a solution of Example 18C (30 mg, 0.05 mmol) in dichloromethane (150 μL) was added triethylamine (150 μL, 0.11 mmol) and acetic anhydride (6 μL, 0.06 mmol) and the mixture stirred at room temperature for 16 hours. Solvent was removed in vacuo and the crude residue was dissolved in dichloromethane (0.5 mL) and trifluoroacetic acid (0.5 mL) and the mixture was stirred at room temperature for 2 hours. Solvent was removed in vacuo and the crude residue was dissolved in dichloromethane (0.5 mL) and triethylamine (150 μL, 0.11 mmol) was added followed by methanesulfonyl chloride (10 μL, 0.11 mmol). The mixture was stirred at room temperature for 1.5 hours and the solvent was removed in vacuo and the crude residue was dissolved in ethyl acetate (0.5 mL) and 1N NaOH (0.5 mL) and the solution stirred at room temperature for 16 hours. 1N HCl was added dropwise until acidic pH, then the mixture was extracted with ethyl acetate (3×5 mL) and the organic extracts were combined and dried (MgSO4). The drying agent was filtered off and the solvent was removed in vacuo to give a crude residue which was purified by column chromatography on silica gel (5% methanol/chloroform) to give the title compound as a colorless solid. MS (ESI) m/z 561 (M+H+). 1H NMR (d6-DMSO) δ 10.03 (s, 1H), 8.04, 8.02 (d, 1H), 7.55-7.25 (m, 6H), 3.07, 3.06 (d, 3H), 2.01-1.59 (m, 2H), 1.82 (s, 3H), 1.31-1.08 (m, 2H), 1.01-0.84 (m, 1H), 0.71-0.62 (m, 6H).

Provenance & Evidence