Hydrochloric Acid → 5-(4-Chloro-2-(1H-pyrazol-4-YL)phenyl)-N-(1,2,4-thiadiazol-5-YL)naphthalene-2 sulfonamide

Participants

Reaction Conditions

Reaction Steps

A pressure vessel was charged with 5-(2-bromo-4-chlorophenyl)-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (0.8 g, 1.268 mmol), potassium carbonate (1.227 g, 8.88 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (0.748 g, 2.54 mmol), tetrakis(triphenylphosphine)palladium(0) (0.147 g, 0.127 mmol), dioxane (8.45 mL) and water (4.23 mL). The reaction was heated in a microwave at 100° C. for 30 min. The reaction mixture was cooled to room temperature and 2N HCl (10 mL) was then added dropwise to neutralize the base. The aqueous layer was then washed with DCM (three times). The organic layers were combined and dried over sodium sulfate, filtered over a layer of diatomaceous Earth® (diatomaceous earth) and concentrated under a vacuum to provide a yellow oil. To this oil was added DCM (12.68 mL, 1.268 mmol) and TFA (0.488 mL, 6.34 mmol). The resulting mixture was stirred for 1 h at rt. LC/MS indicated that the dimethoxybenzyl (DMB)-protected intermediate remained. The mixture was then heated to 50° C. for 1 h. LC/MS indicated that the desired product (M+H=467.8) was generated. The mixture was concentrated, diluted with DCM (3 mL) and purified by reverse phase HPLC using a Phenomenex Gemini 5 μm, C18, 110 Å, 150×30 mm column eluting with a mixture of 0.1% TFA in acetonitrile/water. The fractions containing product were dried to provide a white solid. 5-(4-chloro-2-(1H-pyrazol-4-yl)phenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (0.165 g, 0.352 mmol). 1H NMR (500 MHz, DMSO-d6) δ ppm 2.08 (s, 2H) 2.54 (s, 1H) 7.02 (br. s., 2H) 7.30 (d, J=8.23 Hz, 1H) 7.40-7.47 (m, 2H) 7.56 (d, J=7.05 Hz, 1H) 7.65 (dd, J=8.87, 1.92 Hz, 1H) 7.69-7.76 (m, 1H) 7.79 (d, J=2.14 Hz, 1H) 8.26 (d, J=8.23 Hz, 1H) 8.44 (s, 1H) 8.53 (d, J=1.71 Hz, 1H); m/z (ESI) 467.8 (M+H)+.

Provenance & Evidence