Methyl iodide → Sodium (4r)-4-methyl-4-(3-methylbutyl)-2-{7-[methyl(methylsulfonyl)amino]-1,1-dioxido-4h-1,2,4-benzothiadiazin-3-yl}-3-oxo-3,4-dihydronaphthalen-1-olate

Participants

Reaction Steps

To a solution of Example 39I (104 mg, 0.193 mmol) in 3 mL of water was added 0.997 N NaOH (0.194 mL, 0.193 mmol). After stirring for 2 hours, the reaction mixture was concentrated to dryness. To a solution of the resulting residue in 3 mL of dimethylformamide was added methyl iodide (0.012 mL, 0.193 mmol). After stirring at room temperature overnight, the reaction solution was concentrated and chromatographed on silica gel eluting with hexane followed by 60% and 80% ethyl acetate in hexane. The resulting yellow solid was suspended in 3 mL of water and 0.997 N NaOH was added (0.160 mL, 0.160 mmol). After stirring for 4 hours, the suspension was lyophilized to 84 mg (79%) of a yellow solid. 1H NMR (300 MHz, DMSO-d6): δ ppm 0.46 (m, 1H) 0.69 (t, J=7.17 Hz, 6H) 0.82 (m, 1H) 1.28 (m, 1H) 1.39 (s, 3H) 1.73 (m, 1H) 2.15 (m, 1H) 2.97 (s, 3H) 3.27 (s, 3H) 7.33 (m, 2H) 7.46 (m, 2H) 7.57 (dd, J=8.82, 2.21 Hz, 1H) 7.66 (d, J=2.57 Hz, 1H) 8.05 (d, J=7.72 Hz, 1H) 15.64 (s, 1H). MS (ESI−) m/z 530 (M−H)−.

Provenance & Evidence