Dichloromethane → 2-Chloro-4-[7-(2-chloro-pyridin-4-yl)-benzo[b]thiophen-2-yl]-pyrimidine

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Reaction Steps

In a 500 mL round bottom flask, cool a solution of 4-benzo[b]thiophen-7-yl-2-chloro-pyridine (13 g, 53.1 mmol) and triisopropylborate (20 g, 106 mmol) in THF (150 mL) to −70° under nitrogen. To the cooled solution, add lithium diisopropylamide (2 M in THF, 53 mL, 106 mmol) gradually over a period of 30 min. Stir the mixture continually for an additional 1 hour in the cooling bath. Gradually transfer the mixture into a refluxing solution of 2,4-dichloro-pyrimidine (12 g, 106 mmol), [1,1′-bis(diphenyl-phosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (2.2 g, 53 mmol) and sodium carbonate (35 mL, 3 M, 106 mmol) in THF (150 mL) over a period of 30 min. Reflux for an additional 1 hour. Cool the mixture to room temperature and dilute with 500 mL of chloroform/isopropanol (3/1) and 200 mL of water. Collect the resulting solid by filtration and reserve the chloroform/isopropanol/water mixture. Wash the solid with dichloromethane and dry it under vacuum. Separate the layers of the chloroform/isopropanol/water mixture. Wash the organic phase with water and saturated aqueous sodium chloride, dry over sodium sulfate and concentrate in vacuo to give a brown residue. Purify the residue by flash column chromatography (10% methanol in dichloromethane) to afford additional product. Combine the two portions to give the title compound (13 g, 68%) MS (ES) m/z 358 [M+1]+.

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