3,5-Dimethylisoxazole-4-isocyanate → (+/-)-1-(3,5-Dimethyl-isoxazol-4-yl)-3-(3-fluoro-4-{2-[4-(4-fluoro-phenyl)-2-methyl-5-oxo-4-propyl-4,5-dihydro-imidazol-1-yl]-acetyl}-phenyl)-urea

Participants

Reaction Steps

Synthesis in analogy to Example 7 and Example 10 starting from (+/−)-3-[2-(4-amino-2-fluoro-phenyl)-2-oxo-ethyl]-5-(4-fluoro-phenyl)-2-methyl-5-propyl-3,5-dihydro-imidazol-4-one and 4-isocyanato-3,5-dimethyl-isoxazole to yield (+/−)-1-(3,5-dimethyl-isoxazol-4-yl)-3-(3-fluoro-4-{2-[4-(4-fluoro-phenyl)-2-methyl-5-oxo-4-propyl-4,5-dihydro-imidazol-1-yl]-acetyl}-phenyl)-urea. The compound is suspended in a 1 molar aqueous sodium hydroxide solution. Subsequently iodomethane (1 equivalent) and tetrabutyl ammonium chloride (1 equivalent) are added and the mixture is stirred for 18 hours at room temperature. Subsequently the product is extracted with dichloromethane and subjected to preparative LC purification (method 3) to yield (+/−)-1-(3,5-dimethyl-isoxazol-4-yl)-3-(3-fluoro-4-{2-[4-(4-fluoro-phenyl)-2-methyl-5-oxo-4-propyl-4,5-dihydro-imidazol-1-yl]-acetyl}-phenyl)-1,3-dimethyl-urea LC/MS at 254 nm; [M+H] 552; Rt 3.502 min.

Provenance & Evidence