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
Reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:27])[CH2:9][N:10]2[C:14](=[O:15])[C:13]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)([CH2:16][CH2:17][CH3:18])[N:12]=[C:11]2[CH3:26])=[C:4]([F:28])[CH:3]=1.[N:29]([C:32]1[C:33]([CH3:38])=[N:34][O:35][C:36]=1[CH3:37])=[C:30]=[O:31]>>[CH3:38][C:33]1[C:32]([NH:29][C:30]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([C:8](=[O:27])[CH2:9][N:10]3[C:14](=[O:15])[C:13]([C:19]4[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=4)([CH2:16][CH2:17][CH3:18])[N:12]=[C:11]3[CH3:26])=[C:4]([F:28])[CH:3]=2)=[O:31])=[C:36]([CH3:37])[O:35][N:34]=1Participants
Procedure
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.
Sources & evidence
- ORD record
- ord-370eefe20256469f99f3f0c98ec6d27a
- Source dataset
- uspto-grants-2010_08
- Patent number
- US07786155B2
Reaction notes
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