Dicyclohexylcarbodiimide → HCID 178495112, compound

Participants

Reaction Conditions

Reaction Steps

A KIMAX® tube is charged with 3-amino-6-[2-cyclopropyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]pyridin-2-ol (0.7 g, 2.13 mmol) and ethanol (7 mL). (3S)-3-isothiocyanato-1-methoxy-butane (0.46 g, 3.2 mmol) is added, the flask sealed, and the mixture is heated to 85° C. After 16 h, N,N′-dicyclohexylcarbodiimide (0.88 g, 4.26 mmol) is added and the mixture is stirred for 4 h at 85° C. in the sealed tube. After this time, additional N,N′-dicyclohexylcarbodiimide (0.44 g, 2.13 mmol) is added to the mixture. Heating is continued at 85° C. overnight. After this time, additional N,N′-dicyclohexyl-carbodiimide (0.88 g, 4.26 mmol) is added to the mixture, and heating is continued at 85° C. for 4 h. The crude reaction is concentrated under reduced pressure, and the residue is purified by normal phase chromatography (120 g silica-gel cartridge, dichloromethane-ethanol gradient). The fractions containing the desired compound are further purified by semi-preparative reverse phase high performance (LC/MS) using an XBRIDGE™ column (5 μm, 19×100 mm) and an isocratic program of 36% of acetonitrile in NH4HCO3 20 mM (pH 9), in 5 min at flow 25 mL/min to afford the title compound (0.15 g, 16%). LCES/MS m/z 440 (M+1); [α]D22+58.60°, (c=0.50, methanol).

Provenance & Evidence