Ethyl isocyanate → HCID 67219000, compound

Participants

Reaction Steps

To a solution of 0.045 g of 4′-{4-[5,6-dichloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yloxymethyl]-piperidin-4-yl}-biphenyl-3-carbonitrile (0.073 mmol, 1 eq) in 0.7 mL of dichloromethane was added ethyl isocyanate (6.5 μL, 0.088 mmol, 1.2 eq) and 15.4 μL of diisopropylethyl amine (0.088 mmol, 1.2 eq) and the resulting mixture was stirred at room temperature for 16 h. The solvent was removed by rotary evaporation to yield the crude product which was purified by preparative TLC eluting with 10% methanol in dichloromwthane to give 0.030 g of 4-(3′-cyano-biphenyl-4-yl)-4-[5,6-dichloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yloxymethyl]-piperidine-1-carboxylic acid ethylamide. This intermediate was dissolved in 2 mL of tetrahydrofuran and 0.080 g of tetrabutylammonium fluoride on silica gel (1.0-1.5 mmol/g, 2 eq) was added. The mixture was heated at 60° C. for 16 h then filtered and the resin washed with 10 mL of tetrahydrofuran. The filtrate was concentrated by rotary evaporation and the crude product was purified by flash silica gel chromatography eluting with 1% methanol in dichloromethane with 3% triethylamine to give 0.0054 g of the desired product 4-(3′-cyano-biphenyl-4-yl)-4-(5,6-dichloro-1H-benzoimidazol-2-yloxymethyl)-piperidine-1-carboxylic acid ethylamide 58. MS (ESI): Calcd m/z for C29H27Cl2N5O2.H+=548.2; found m/z=547.8/549.8 [(M+1)+/(M+3)+].

Provenance & Evidence