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1,2-Dichloroethane → N-benzyl-1-(1-(4-chlorobenzyl)-7-methyl-1H-indole-2-carbonyl)piperidine-4-carboxamide

HRID 83681
Notes
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Reaction equation

HRID 83681 reaction equation
[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[CH3:16])[CH:9]=[C:8]2[C:17](O)=[O:18])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH2:45]([NH:52][C:53]([CH:55]1[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]1)=[O:54])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>CCOC(C)=O.CN(C=O)C>[CH2:45]([NH:52][C:53]([CH:55]1[CH2:60][CH2:59][N:58]([C:17]([C:8]2[N:7]([CH2:6][C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:21][CH:20]=3)[C:15]3[C:10]([CH:9]=2)=[CH:11][CH:12]=[CH:13][C:14]=3[CH3:16])=[O:18])[CH2:57][CH2:56]1)=[O:54])[C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 3868064N-benzylpiperidine-4-carboxamideHCID 683797591-(4-chlorobenzyl)-7-methyl-1H-indole-2-carboxylic acid

Product 1

HCID 66571684
N-benzyl-1-(1-(4-chlorobenzyl)-7-methyl-1H-indole-2-carbonyl)piperidine-4-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

The following was added to sequentially to DMF (2 mL): 1-(4-chlorobenzyl)-7-methyl-1H-indole-2-carboxylic acid (50 mg, 0.167 mmol), DIPEA (0.10 mL, 0.584 mmol), EDC (38 mg, 0.200 mmol), and HOBT (31 mg, 0.200 mmol). This was allowed to stir for 30 min at rt, after which time the crude N-benzylpiperidine-4-carboxamide (˜36 mg, 0.20 mmol) was added. The reaction was stirred at rt for 18 h, at which time the reaction was diluted with 1:1 EtOAc:diethyl ether and washed with 10% aq. sodium carbonate (2×), dried over magnesium sulfate, and concentrated. The residue was purified via silica gel flash chromatography (20 g silica, 50% EtOAc/Hexanes) to afford the title compound as a white powder. (Yield: 39 mg, 0.078 mmol, 47%) 1H NMR (400 MHz, CDCl3) 7.50, 7.38-7.26, 7.18, 7.05-6.97, 6.81, 6.63, 5.72, 5.66-5.57, 4.70-3.89, 4.44, 2.86-2.66, 2.57, 2.32-2.23, 1.77

Workup

  1. stirringThe reaction was stirred at rt for 18 h, at which time the reaction
  2. washdiethyl ether and washed with 10% aq. sodium carbonate (2×)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified via silica gel flash chromatography (20 g silica, 50% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-add255bcb05444f6877328775a1193d3
Source dataset
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08846684B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes