Dimethylformamide → tert-butyl 8-(6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1-methyl-1H-indol-3-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

A vial was charged with N-(2,4-dimethoxybenzyl)-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (Intermediate H)(0.188 g, 0.330 mmol), tert-butyl 8-bromo-3,4-dihydroisoquinoline-2(1H)-carboxylate (0.257 g, 0.824 mmol), potassium phosphate (0.315 g, 1.483 mmol), and PdCl2(dppf)-CH2Cl2 adduct (0.027 g, 0.033 mmol). DMF (2.197 ml) was added, and the vial was flushed with argon, sealed, and stirred at 85° C. for two hours. Additional tert-butyl 8-bromo-3,4-dihydroisoquinoline-2(1H)-carboxylate (Oakwood Inc., West Columbia, S.C.) (0.257 g, 0.824 mmol) was added and the reaction was stirred at 85° C. for two hours. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with brine, dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 40 g silica gel column (Teledyne Isco, Lincoln, Nebr.), gradient elution 0 to 100% EtOAc:Hex) to afford tert-butyl 8-(6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1-methyl-1H-indol-3-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate as a light yellow solid.

Provenance & Evidence