2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl → 2-Morpholino-4-(naphthalen-2-ylmethyl)thiazole-5-sulfonamide

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Reaction Steps

To a dried flask was added 4-bromo-2-morpholinothiazole-5-sulfonamide (194 mg, 0.591 mmol), THF (4.79 mL), palladium(II) acetate (1.33 mg, 0.00591 mmol) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (4.85 mg, 0.0118 mmol). The mixture was stirred for 5 minutes, and a 0.500 M solution of 2-napthylmethylzinc bromide in THF (4.14 mL, 2.04 mmol) was then added dropwise over 30 minutes. The reaction was stirred at room temperature for 1 hour and quenched with saturated ammonium chloride (10 mL). The reaction was extracted with ethyl acetate (2×25 mL) and the combined organic layers were washed with water (15 mL), dried and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate/DCM=0/100→40/60) which gave a mixture of the desired product with residual 4-bromo-2-morpholinothiazole-5-sulfonamide. This material was purified by preparative reverse phase chromatography to give 51 mg (22% yield) of the title compound as a white solid. LC/MS (FA) ES+ 390. 1H NMR (400 MHz, DMSO-d6) δ: 7.85-7.77 (m, 4H), 7.71 (bs, 2H), 7.50-7.42 (m, 3H), 4.25 (s, 2H), 3.64-3.61 (m, 4H), 3.35-3.32 (m, 4H).

Provenance & Evidence