Methanol → HCID 57954408, compound

Participants

Reaction Steps

NEt3 (6.6 ml, 47.3 mmol) was added to a stirred solution of 2-cyanoisonicotinic acid (7.00 g, 47.3 mmol) in toluene (500 ml). The mixture was cooled to 0° C., before being treated with isobutyl chloroformate (6.1 ml, 47.3 mmol). Stirring was continued at 0° C. for 10 min, then the mixture was allowed to warm to rt over 1 h, before being treated with (N-hydroxycarbamimidoylmethyl)carbamic acid tert-butyl ester (7.44 g, 39.4 mmol) and dried 4 Å molecular sieves (40 g). The reaction was heated under reflux for 16 h. On cooling, the mixture was filtered through celite, washing with MeOH. The combined filtrates were concentrated in vacuo, then the residue was dissolved in EtOAc. The EtOAc solution was washed with saturated aqueous Na2CO3 and brine, before being dried (MgSO4). Filtration, solvent evaporation, and column chromatography (IH-EtOAc, 7:3) furnished [5-(2-cyanopyridin-4-yl)-[1,2,4]oxadiazol-3-ylmethyl]carbamic acid tert-butyl ester m/z (ES+)=603.2 [2M+H]+. A stirred solution of this carbamate (1.95 g, 6.5 mmol) in CHCl3 (50 ml) was treated with TMS-I (2.2 ml, 15.6 mmol). After 10 min, the reaction was treated with MeOH (2.5 ml, 62.2 mmol), then stirring was continued for a further 10 min. The solvents were evaporated off under reduced pressure, then the residue was dissolved in MeOH and adsorbed onto SiO2. Column chromatography (EtOAc then EtOAc-MeOH, 9:1) afforded the title compound: m/z (ES+)=202.0 [M+H]+.

Provenance & Evidence