Potassium Carbonate → 1-methyl-3-(1-methylethyl)-5-(6-methyl-3-pyridinyl)-1H-indole-7-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a 40 mL vial was added 5-bromo-1-methyl-3-(1-methylethyl)-1H-indole-7-carboxylic acid (0.850 g, 2.87 mmol), (6-methyl-3-pyridinyl)boronic acid (0.432 g, 3.16 mmol), K2CO3 (1.190 g, 8.61 mmol) and PdCl2(dppf)-CH2Cl2 adduct (0.234 g, 0.287 mmol). The reagents were diluted with 1,2-dimethoxyethane (21.5 mL) and water (7.2 mL). The reaction was heated to 100° C. with stirring for 30 minutes, then filtered and concentrated under vacuum to give a thick brown residue. The residue was diluted with saturated NaHCO3 (15 mL) and water (10 mL) and aqueous solution washed with EtOAc (3×40 mL). The aqueous solution was then slowly added to a rapidly stirred, cooled (0° C.) solution of 1 N HCl. The mixture was stirred for 20 min and the solids collected by vacuum filtration. LCMS showed the solids contained only a small amount of desired product. The solids were discarded. The acidic aqueous solution was extracted with EtOAc (3×250 mL). LCMS showed the desired product in both layers. Thus, both the organic and aqueous layers were concentrated. The residue was purified by reverse phase HPLC (Gemini 50×100 mm column, acetonitrile and 0.1% formic acid/water) to give 1-methyl-3-(1-methylethyl)-5-(6-methyl-3-pyridinyl)-1H-indole-7-carboxylic acid (590 mg, 66.6% yield) as light tan solid. MS (ES) [M+H]+ 309.5.

Provenance & Evidence