Lithium Hexamethyldisilazide → 4-((4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)amino)-N-(2,4-dimethoxybenzyl)-3-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

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Reaction Steps

A round-bottom flask was charged with N-(2,4-dimethoxybenzyl)-4-fluoro-3-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (INTERMEDIATE M) (189 mg, 0.416 mmol), 4-chloro-2-(1-methyl-1H-pyrazol-5-yl)aniline (the product of STEP 1 in the preparation of INTERMEDIATE F) (95 mg, 0.457 mmol), and THF (2079 μl) to give a brown solution. The flask was cooled in an ice bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (1248 μl, 1.248 mmol) was added dropwise over 1 minute to give a dark maroon mixture. After 10 min, the mixture was diluted with a saturated aq. ammonium chloride solution and water, then extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The crude product was purified by chromatography on silica gel (20 to 70% EtOAc/heptane) give 4-((4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)amino)-N-(2,4-dimethoxybenzyl)-3-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (197.46 mg, 0.308 mmol, 73.9% yield) as a bright orange solid. m/z (ESI) 642.0 (M+H)+.

Provenance & Evidence