N,N-Diethylaniline → 1H-Indole-2-carboxamide

HRID 393576

Reaction equation

HRID 393576 reaction equation
CC[N:3](C1C=CC=CC=1)CC.[NH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[C:13]1[C:21]([OH:23])=O.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>C1COCC1>[NH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[C:13]1[C:21]([NH2:3])=[O:23]

Participants

6

Reactant 4

HCID 7061N,N-DiethylanilineHCID 72899Indole-2-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 5948321H-Indole-2-carboxamideYield 327%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

Diethylaniline (0.33 μL, 2.1 μmol, 1.1 equiv) was added in one portion to a stirred solution of the amine (1.0 mg, 1.9 μmol, 1 equiv) in THF (0.15 mL) at 0° C. under an argon atmosphere and the solution was stirred for 5 min. Indole-2-carboxylic acid (0.40 mg, 2.5 μmol, 1.3 equiv), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.48 mg, 2.5 μmol, 1.3 equiv) and 1-hydroxybenzotriazole (0.31 mg, 2.3 μmol, 1.2 equiv) were then added separately, each in one portion, to the above solution at 0° C. The reaction mixture was warmed to 23° C. over 15 h 30 min, then was quenched with saturated aqueous ammonium chloride solution (3 mL). The mixture was diluted with ethyl acetate (10 mL) and the layers were separated. The aqueous layer was extracted with ethyl acetate (10 mL) and the combined organic layer was dried over sodium sulfate. Concentration in vacuo left a white solid, which was purified by flash column chromatography (60% ethyl acetate-hexanes) to give the indole-2-carboxylic acid amide derivative (1.1 mg, 87%) as a white solid.

Workup

  1. customat 0° C
  2. customwas quenched with saturated aqueous ammonium chloride solution (3 mL)
  3. additionThe mixture was diluted with ethyl acetate (10 mL)
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with ethyl acetate (10 mL)
  6. dry with materialthe combined organic layer was dried over sodium sulfate
  7. concentrationConcentration in vacuo
  8. waitleft a white solid, which
  9. customwas purified by flash column chromatography (60% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-f6e0d1663bfc40c08267e40cb1de1039
Source dataset
uspto-grants-2004_10
Patent number
US06809099B2

Linked notes

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