HCID 20786195, compound → (E)-2-{4-[2-(2-tert-butoxycarbonylamino-phenylcarbamoyl)-vinyl]-phenyl}-5-chloro-pentanoic acid methyl ester
Reaction equation
BrC1C=CC(C(CCCCl)C(O)=O)=CC=1.[CH3:16][O:17][C:18](=[O:31])[CH:19]([C:24]1[CH:29]=[CH:28][C:27](Br)=[CH:26][CH:25]=1)[CH2:20][CH2:21][CH2:22][Cl:23].[C:32]([O:36][C:37](=[O:50])[NH:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[NH:45][C:46](=[O:49])[CH:47]=[CH2:48])([CH3:35])([CH3:34])[CH3:33]>>[CH3:16][O:17][C:18](=[O:31])[CH:19]([C:24]1[CH:29]=[CH:28][C:27](/[CH:48]=[CH:47]/[C:46](=[O:49])[NH:45][C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[NH:38][C:37]([O:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:50])=[CH:26][CH:25]=1)[CH2:20][CH2:21][CH2:22][Cl:23]Participants
Procedure
Key building block (E)-2-{4-[2-(2-tert-butoxycarbonylamino-phenylcarbamoyl)-vinyl]-phenyl}-5-chloro-pentanoic acid methyl ester (VIII) can be prepared according to Scheme 7. Starting with commercially available 4-(bromo-phenyl)-acetonitrile (XVI), deprotonation with strong base followed by alkylation using 1-bromo-3-chloropropane gives 2-(4-bromo-phenyl)-5-chloro-pentanenitrile (XXXII). Hydrolysis of XXXII under acidic conditions furnishes 2-(4-bromo-phenyl)-5-chloro-pentanoic acid (XXXIII). Nucleophilic acyl substitution converts XXXIII to 2-(4-bromo-phenyl)-5-chloro-pentanoic acid methyl ester (XXXIV), which undergoes Heck reaction with (2-acryloylamino-phenyl)-carbamic acid tert-butyl ester to give key building block (E)-2-{4-[2-(2-tert-butoxycarbonylamino-phenylcarbamoyl)-vinyl]-phenyl}-5-chloro-pentanoic acid methyl ester (VIII).
Sources & evidence
- ORD record
- ord-a279fd25503e48e685d3c534916631cc
- Source dataset
- uspto-grants-2012_06
- Patent number
- US08202866B2
Reaction notes
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