5-Chloro-2-nitrobenzoic acid → 5-chloro-N-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-2-nitro-benzamide
Reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N+:11]([O-:13])=[O:12])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C.[CH3:29][O:30][C:31]1[CH:32]=[C:33]([NH2:45])[CH:34]=[CH:35][C:36]=1[O:37][CH2:38][CH2:39][N:40]1[CH2:44][CH2:43][CH2:42][CH2:41]1>ClCCl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N+:11]([O-:13])=[O:12])=[C:6]([CH:10]=1)[C:7]([NH:45][C:33]1[CH:34]=[CH:35][C:36]([O:37][CH2:38][CH2:39][N:40]2[CH2:41][CH2:42][CH2:43][CH2:44]2)=[C:31]([O:30][CH3:29])[CH:32]=1)=[O:9]Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
5-Chloro-2-nitrobenzoic acid [Aldrich] (600 mg, 3 mmol) was suspended in dichloromethane (5 ml) and treated with oxalyl chloride (2 ml) and DMF (1 drop). On stirring, an immediate effervescence occurred which ceased after 1 hour. The solvent was removed in vacuo and the residue dissolved in dichloromethane (10 ml) and treated successively with DIEA resin (3.1 mmol/g, 1.95 g) and 3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenylamine (650 mg, 3 mmol). The mixture was stirred at RT for 16 hours then filtered, evaporated, and the residue purified by flash chromatography (methanol-dichloromethane-aqueous ammonia) to afford 5-chloro-N-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-2-nitro-benzamide as a yellow foam;
Workup
- customThe solvent was removed in vacuo
- dissolutionthe residue dissolved in dichloromethane (10 ml)
- stirringThe mixture was stirred at RT for 16 hours
- filtrationthen filtered
- customevaporated
- customthe residue purified by flash chromatography (methanol-dichloromethane-aqueous ammonia)
Sources & evidence
- ORD record
- ord-29291fdeefbd4d9f93d408e2164bf8e4
- Source dataset
- uspto-grants-2007_05
- Patent number
- US07220777B2
Reaction notes
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