Sodium Carbonate → Ethyl 4-(4-cyanophenyl)-6-methyl-2-oxo-3-[3-(2-thienyl)benzyl]-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of ethyl 3-(3-bromobenzyl)-4-(4-cyanophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-5-carboxylate (Example 35) (40 mg, 0.07 mmol), 2-thiophen-boronic acid (10.69 mg, 0.08 mmol), 2 M aqueous sodium carbonate (100 μl, 0.2 mmol) and bis(triphenylphosphine)palladium(II)chloride (4.7 mg, 0.01 mmol) in dimethylformamide (2.0 ml) is stirred at 90° C. overnight (16 h). Additional bis(triphenylphosphine)palladium(II) chloride (4.7 mg, 0.01 mmol) is added, and the reaction is stirred at 90° C. for another 24 h, after which time additional bis(triphenylphosphine)palladium(II) chloride (4.7 mg, 0.01 mmol) is added and the reaction stirred 3 h longer at 90° C. The reaction mixture is diluted with dimethylformamide (5 ml) and purified directly by preparative HPLC (RP18 column; eluent: acetonitrile/0.1% aq. formic acid 10:90→90:10). The product fractions are concentrated and pulled through a thin layer of silica gel 60 with dichloromethane as eluent. Concentration in vacuo gives the title compound.

Provenance & Evidence