Potassium Carbonate → 6-chloro-5-[4-(1-hydroxy-2-methylpropan-2-yl)-3-methoxyphenyl]-N-(methylsulfonyl)-1H-indole-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

A round bottomed flask was charged with a 1:1 mixture of 5-bromo-6-chloro-1H-indole-3-carbaldehyde and 5-bromo-6-chloro-N-(methylsulfonyl)-1H-indole-3-carboxamide (96 mg, 0.27 mmol) as prepared in step 1, 2-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-methoxyphenyl]-2-methylpropan-1-ol (40 mg, 0.14 mmol) (prepared from 2-(4-Bromo-2-methoxyphenyl)-2-methylpropan-1-ol in a manner similar to Example 8, Step 4), potassium carbonate solution (2.0M, 0.27 mL), toluene (0.75 mL), ethanol (0.28 mL), and THF (0.28 mL) then degassed with nitrogen for 5 minutes. PddppfCl2 was then added and the reaction heated to 110° C. for 3 hours. The reaction was then cooled to rt, diluted with water and ethyl acetate. The layers were separated and the aqueous extracted with ethyl acetate×3. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The crude residue was then dissolved in DMSO and purified by reverse phase HPLC to provide the title compound as an ammonium salt (8.0 mg). MS (ES−): 449.1 (M−H)—HPLC retention time: 1.86 min, Waters XBridge C18, 5 μm, 4.6×50 mm, 0.03% NH4OH, 5-95% acetonitrile in water gradient over 4.0 min, hold at 95% acetonitrile in water to 5.0 min, flow 2.0 mL/min.

Provenance & Evidence