Diisopropylamine → 2-(2-Chloro-5-methylpyrimidin-4-yl)-benzo[b]thiophene-6-sulfonic acid benzhydrylamide

Participants

Reaction Conditions

Reaction Steps

To a solution of diisopropylamine (2.09 mL, 14.87 mmol) in dry THF (10 mL) is added a solution of n-butyllithium (1.6 M in hexane, 9.14 mL, 14.62 mmol) at −78° C. under a nitrogen atmosphere, the mixture is stirred for 30 minutes. A solution of benzo[b]thiophene-6-sulfonic acid benzhydrylamide (925 mg, 2.44 mmol) and triisopropylborate (2.87 mL, 12.43 mmol) in dry THF (10 mL) is added. The mixture is slowly warmed to 10° C. over 1 hour and stirred at room temperature for 30 minutes. A solution of sodium carbonate (2 M in water, 3.78 mL) is added followed by the addition of 2,4 dichloro5-methylpyrimidine (517 mg, 3.17 mmol) and (1,1′-bis(diphenylphosphino)ferrocene)palladium (II) chloride (99.6 mg, 0.122 mmol). The mixture is heated at 60° C. for 1.5 hours then cooled to room temperature. Water (40 mL) is added and the mixture is extracted with EtOAc (3×40 mL). The organic layers are dried (MgSO4) and concentrated. The residue is chromatographed on silica gel, eluting with hexanes/EtOAc 90:10 to 40:60, to give the title compound as a yellow solid (457 mg, 37% yield).

Provenance & Evidence