Hydrochloric Acid → n-({3-[(4r)-4-(3,3-Dimethylbutyl)-1-hydroxy-4-methyl-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4h-thieno [2,3-e][1,2,4]thiadiazin-7-yl}methyl)-n-methylmethanesulfonamide

Participants

Reaction Conditions

Reaction Steps

A solution of Example 187 (124 mg, 0.22 mmol) in 2 mL of N,N-dimethyl formamide was cooled to 0° C., treated with sodium hydride (24 mg, 60% in oil, 0.5 mmol), stirred at 0° C. for 1 h, stirred at room temp for 30 min, treated with methyl iodide (9 μL, 0.14 mmol), stirred for 2 h, treated with methyl iodide (7 μL, 0.11 mmol), and stirred at room temp over night. The mixture was diluted with water and ethyl acetate, treated with 1N HCl, and extracted with ethyl acetate. The organic phase was washed with 2× 10 mL of H2O and concentrated in vacuo. The crude material was chromatographed on silica gel with a gradient of methanol in dichloromethane (0-5%) to afford the title compound (48 mg, 39% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 0.40 (td, J=12.8, 3.7 Hz, 1H), 0.72 (s, 9H), 0.81 (td, J=12.9, 4.4 Hz, 1H), 1.56 (s, 3H), 2.01 (m, 1H), 2.21 (td, J=12.8, 4.6 Hz, 1H), 2.85 (s, 3H), 3.02 (s, 3H), 4.39 (s, 2H), 7.32 (s, 1H), 7.50 (m, 1H), 7.71 (m, 2H), 8.12 (d, J=7.8 Hz, 1H), 14.21 (s, 1H); MS (APCI−) m/z 564 (M−H)−.

Provenance & Evidence