1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)-N-((1-methylpiperidin-4-yl)methyl)piperidine-4-carboxamide

HRID 83626

Reaction equation

HRID 83626 reaction equation
[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[C:8]2[C:16]([N:18]2[CH2:23][CH2:22][CH:21]([C:24]([OH:26])=O)[CH2:20][CH2:19]2)=[O:17])=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.[CH3:50][N:51]1[CH2:56][CH2:55][CH:54]([CH2:57][NH2:58])[CH2:53][CH2:52]1>C(Cl)Cl.O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[C:8]2[C:16]([N:18]2[CH2:23][CH2:22][CH:21]([C:24]([NH:58][CH2:57][CH:54]3[CH2:55][CH2:56][N:51]([CH3:50])[CH2:52][CH2:53]3)=[O:26])[CH2:20][CH2:19]2)=[O:17])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 815741-Methylpiperidine-4-methylamineHCID 573857961-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)piperidine-4-carboxylic acid

Product 1

HCID 665713371-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)-N-((1-methylpiperidin-4-yl)methyl)piperidine-4-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)piperidine-4-carboxylic acid (100 mg, 0.252 mmol), 1-hydroxybenzotriazole (68.1 mg, 0.504 mmol) and EDCI (97 mg, 0.504 mmol) were dissolved in DCM (Volume: 4.0 ml). The suspension was stirred at room temperature for 10 minutes where it turned clear. Hunig'sBase (0.132 ml, 0.756 mmol) and (1-methylpiperidin-4-yl)methanamine (100 mg, 0.780 mmol) were added. The reaction was stirred at room temperature overnight. It was diluted with water and ethyl acetate. The water layer was washed with another portion of ethyl acetate. The combined organic layer was washed with saturated sodium bicarbonate and saturated sodium chloride. The organic layer was dried over magnesium sulfate, filtered, and concentrated. The resulting crude material was triturated with diethyl ether/ethyl acetate to afford the product as a white solid. (Yield: 83 mg, white solid) 1H-NMR (400 MHz, DMSO-d6) 7.77, 7.62, 7.54, 7.35-7.30, 7.21, 7.13-7.06, 6.72, 5.49, 4.38, 4.02, 2.93, 2.78, 2.42-2.30, 2.17, 1.77, 1.57, 1.45-1.02

Workup

  1. stirringThe reaction was stirred at room temperature overnight
  2. washThe water layer was washed with another portion of ethyl acetate
  3. washThe combined organic layer was washed with saturated sodium bicarbonate and saturated sodium chloride
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting crude material was triturated with diethyl ether/ethyl acetate

Sources & evidence

ORD record
ord-ca4064e8103c40daac5d45239499cdb1
Source dataset
uspto-grants-2014_09
Patent number
US08846684B2

Linked notes

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