反应详情

温度

70 °C

A 500-mL two-neck flask was charged with 5-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (Intermediate D, 10 g, 19.22 mmol), palladium (ii) acetate (0.216 g, 0.961 mmol), and Xantphos (1.112 g, 1.922 mmol). Triethylamine (77 ml, 19.22 mmol), toluene (48.0 ml), and methanol (15.55 ml, 384 mmol) were added, and the reaction was fitted with a reflux condenser. The reaction was evacuated and back-filled with carbon monoxide three times, and then the reaction was heated to 70° C. and stirred for four hours under an atmosphere of carbon monoxide. The reaction was filtered through a pad of diatomaceous earth, which was thoroughly washed with ethyl acetate. The filtrate was concentrated, triturated in ethyl acetate and filtered. The solid was collected and the filtrate was concentrated. The trituration procedure was repeated twice, and the solids resulting from each trituration were combined with the previously isolated material. After the third trituration, the mother liquor was purified via column chromatography (RediSep Gold 80 g silica gel column, gradient elution 0-50% EtOAc:Heptane). The clean product fractions were combined with the previously isolated material and the resulting slurry was concentrated to afford methyl 6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1-naphthoate as a light yellow solid. m/z (ESI) 500.3 (M+H)+.

1. customthe reaction was fitted with a reflux condenser
2. customThe reaction was evacuated
3. additionback-filled with carbon monoxide three times
4. filtrationThe reaction was filtered through a pad of diatomaceous earth, which
5. washwas thoroughly washed with ethyl acetate
6. concentrationThe filtrate was concentrated
7. customtriturated in ethyl acetate
8. filtrationfiltered
9. customThe solid was collected
10. concentrationthe filtrate was concentrated
11. customthe solids resulting from each trituration
12. customAfter the third trituration, the mother liquor was purified via column chromatography (RediSep Gold 80 g silica gel column, gradient elution 0-50% EtOAc:Heptane)
13. concentrationthe resulting slurry was concentrated