Carbamate → (3-Cyano-5-methoxy-phenyl)-carbamic acid 4-cyclopropanesulfonylaminocarbonyl-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.0*4,6*]octadec-7-en-17-yl ester

Participants

Reaction Conditions

Reaction Steps

The alcohol 1h (15 mg) was dissolved in dry DCE and 20 mg of sodium bicarbonate was added, followed by 2 ml of a phosgene solution in toluene (20%). The reaction mixture was stirred at room temperature for 3 h (full conversion to chloroimidate according to LC-MS) and then concentrated by rotary evaporation and dried from excess of phosgene in high vacuum (1.5 h). The dry reaction mixture was transferred into a “microwave” vial (2-5 ml), mixed with dry DCE (3 ml), 3-amino-5-methoxy-benzonitrile (2 eq), potassium carbonate (9 mg, 1.5 eq), pulverized molecular sieves (4 Å, 5 mg) and heated in a microwave at 100° C. for 45 min. The reaction mixture was passed through short pad of silica (eluent DCM, then 10% methanol in DCM). The resulting fractions containing the desired carbamate compound were combined, concentrated by rotary evaporation and purified by column chromatography on YMC silica (15 g, ethyl acetate/petroleum ether 1:3 to remove excess of aniline, followed by dichloromethane and then 2% methanol in dichloromethane) to give the title compound as a powder (15 mg, 8%), [M+H]+ 628.

Provenance & Evidence