Potassium Phosphate, Tribasic → methyl 3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

A brown mixture of methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indole-5-carboxylate (2.32 g, 5.10 mmol), 2-bromo-6-cyclopropylpyrazine (CombiPhos Catalysts, Inc., Princeton, N.J.; 1.116 g, 5.60 mmol), Pd2(dba)3 (0.140 g, 0.153 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (XPhos; 0.146 g, 0.306 mmol), and potassium phosphate (3.24 g, 15.29 mmol) in a mixture of dioxane (45 mL) and H2O (4.50 mL) was sparged with argon then heated at 100° C. for 3 h. Additional 2-bromo-6-cyclopropylpyrazine (CombiPhos Catalysts, Inc., Princeton, N.J.; 550 mg, 2.80 mmol) was added, and the resulting mixture was stirred at 100° C. for 2 h. The reaction was cooled to RT, diluted with DCM (50 mL), and concentrated onto silica gel. Chromatographic purification (silica gel, 0-80% EtOAc/Hex) furnished methyl 3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indole-5-carboxylate (2.22 g, 4.96 mmol, 97%) as a light-yellow solid: MS (ESI, pos. ion) m/z: 448.1 (M+1).

Provenance & Evidence