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

Participants

Reaction Steps

In a vial was added 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) (29 mg, 0.061 mmol), followed by anhydrous THF (1 mL), then NaBH4 (8 mg, 0.211 mmol). The reaction mixture was then capped (not under N2) & stirred at room temperature. Followed by LC/MS. The reaction mixture was diluted with MeOH/drops of H2O/DMSO/TFA (lot of bubbling), filtered (syringe filter), then purified (without workup) 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 5-fluoro-3-((7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)methyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (21-1). HRMS [M+H] calculated; 477.0697, observed; 477.0705. 1H NMR (499 MHz, DMSO): δ 8.49 (s, 1H); 7.79 (d, J=5.5 Hz, 1H); 7.29 (d, J=9.6 Hz, 1H); 7.05-7.02 (m, 2H); 6.87-6.83 (m, 1H); 5.75 (s, 2H); 5.01-4.95 (m, 1H); 4.02-3.92 (m, 1H); 2.99-2.92 (m, 1H); 2.91-2.83 (m, 1H); 2.77-2.68 (m, 1H); 1.91-1.84 (m, 2H); 1.66-1.57 (m, 1H).

Provenance & Evidence