Trifluoroacetic acid → 5-Fluoro-2-oxo-3-((7-oxo-5,6,7,8-tetrahydronaphthalen-1-yl)methyl)-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Participants

Reaction Steps

To a flask containing 3-((3′,4′-dihydro-1′H-spiro[[1,3]dioxolane-2,2′-naphthalen]-8′-yl)methyl)-N-(2,4-dimethoxybenzyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (19-4) (1.65 g, 2.467 mmol) in DCM (10 ml) was added TFA (8 ml, 104 mmol). The reaction mixture (clear pink/purple with R2 addition) was then capped (not under N2) & stirred at room temperature. Followed by LC/MS . . . added 3 additional portions of TFA then after several hours at room temperature the reaction mixture was diluted with DMSO/MeOH, then concentrated (to remove DCM), then filtered to yield a portion of 5-fluoro-2-oxo-3-((7-oxo-5,6,7,8-tetrahydronaphthalen-1-yl)methyl)-N-(1,2,4-thiadiazazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (19-5). The filtrate was then purified by reverse phase chromatography (5-75% MeCN/H2O; 0.1% TFA in AQ; 20 min gradient; Waters 30×150 mm Sunfire 5 micron C18 column); desired fractions concentrated (GENEVAC), then dissolved in MeOH/DCM & concentrated to yield another portion of 5-fluoro-2-oxo-3-((7-oxo-5,6,7,8-tetrahydronaphthalen-1-yl)methyl)-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (19-5). HRMS [M+H] calculated; 475.0541, observed; 475.0528.

Provenance & Evidence