1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 9968816, compound
Reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][Cl:11].[N+:12]([C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][C:19]([C:24](O)=[O:25])=[CH:18]2)([O-:14])=[O:13].CCN=C=NCCCN(C)C>CN(C=O)C>[Cl:11][CH2:10][CH2:9][C:3]1[CH:4]=[CH:5][C:6]([OH:8])=[CH:7][C:2]=1[NH:1][C:24]([C:19]1[NH:20][C:21]2[C:17]([CH:18]=1)=[CH:16][C:15]([N+:12]([O-:14])=[O:13])=[CH:23][CH:22]=2)=[O:25]Participants
Procedure
2-(2-Amino-4-hydroxyphenyl)ethyl chloride was coupled with 5-nitroindole-2-carboxylic acid with EDCI at 0-50° C., preferably at room temperature, in DMF to give 4-(2-chloroethyl)-3-(5-nitroindole-2-carboxamido)phenol in 14% yield. Subsequent catalytic hydrogenation of 4-(2-chloroethyl)-3-(5-nitroindole-2-carboxamido)phenol at 0-50° C., preferably at room temperature, with 5% Pd-C in THF gave an amine which was directly reacted with at 0-50° C., preferably at room temperature, benzoic acid mustard (p-N,N-bis(2-chloroethyl)aminobenzoic acid) and EDCI to give the desired compound 4-(2-chloroethyl)-3-[[5-(4-bis-(2-chloroethyl)amino)benzamido]indole-2-carboxamido]phenol in 24% yield. Reaction of 4-(2-chloroethyl)-3-[[5-(4-bis-(2-chloroethyl)amino)benzamido]indole-2-carboxamido]phenol at 0-50° C., preferably at 5° C., with 4-nitrobenzyl chloroformate and triethylamine gave the prodrug 4-(2-chloroethyl)-O-(4-nitrobenzylcabonato)-3-[[5-(4-bis-(2-chloroethyl)amino)benzamido]indole-2-carboxamido]phenol in 13% yield, after purification by silica gel column chromatography. The structures of all the compounds prepared were confirmed using IR, 1H-NMR (1H and 13C) spectroscopy, and FAB mass spectrometry including accurate mass measurements.
Sources & evidence
- ORD record
- ord-b29a293517474cffa873188f4bb4db76
- Source dataset
- uspto-grants-2003_12
- Patent number
- US06660742B2
Reaction notes
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