Methyl iodide → HCID 89762052, compound

Participants

Reaction Conditions

Reaction Steps

4-(2-Methoxy-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-2-methyl-3-oxo-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (from the product of Step 2 in Example 263; 110 mg, 0.178 mmol) was dissolved in THF (710 μl) in a 5 mL vial and cooled to 0° C. Lithium bis(trimethylsilyl)amide (1.0 m solution in THF, 69.1 μl, 0.355 mmol) was added dropwise, followed by methyl iodide (16.65 μl, 0.266 mmol), and the reaction was stirred for 30 min at 0° C. until reaction was complete by LCMS. Saturated ammonium chloride solution (aq; 5 mL) was added to the reaction mixture and it was warmed to RT, then extracted with EtOAc (3×5 mL), dried organics over Na2SO4, filtered and concentrated via rotary evaporation. Crude 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-2,2-dimethyl-3-oxo-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide was dissolved in DCM (177 μl) then treated with 2,2,2-trifluoroacetic acid (328 μl, 4.42 mmol) and stirred at rt for 30 min until reaction was complete by LCMS. The reaction mixture was concentrated and purified via reverse-phase HPLC with a Waters-Xbridge C18, 19×100 mm, 10 μm column with a gradient 5-95% acetonitrile and water with 0.1% TFA modifier to yield title compound. m/z ESI 514.0 (M+H)+.

Provenance & Evidence