Nitrogen → N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,3,4-thiadiazol-2-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

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Reaction Conditions

Reaction Steps

A round bottom flask was charged with N-(2,4-dimethoxybenzyl)-1,3,4-thiadiazol-2-amine (INTERMEDIATE Y) (0.689 g, 2.74 mmol), a septum and N2 line were attached. THF (4.57 mL) was added and when the solution became homogeneous, it was cooled to −78° C. After 10 min, added a THF solution of 2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonyl chloride (ASDI) (0.621 g, 2.66 mmol) dropwise over 5 minutes (still at −78° C.). When the addition was complete, the cold bath was removed and the mixture was allowed to warm to rt and stirred 18 h. The reaction mixture was poured into sat. aq. NH4Cl, and DCM was added. The layers were separated and the organic layer was extracted with DCM (2×10 mL). The combined organic extracts were dried over Na2SO4 and concentrated under a vacuum. The solution was concentrated for purification by silica gel MPLC. The residue was taken up in minimal DCM and absorbed onto a 25 g loading cartridge and passed through silica gel column (40 g) using 98:2 Heptane:EtOAc to 100% EtOAc gradient to afford N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,3,4-thiadiazol-2-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (0.856 g, 1.909 mmol) as a white amorphous solid. m/z (ESI) 449.0 (M+H)+.

Provenance & Evidence