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Potassium Carbonate → 1-(5-{(S)-1-[(R)-1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-3-yl)-1H-indole-4-carboxylic acid ethyl ester

HRID 880609
Notes
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Reaction equation

HRID 880609 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C@@H:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH3:14])[CH:7]=1.[CH2:23]([O:25][C:26]([C:28]1[C:29]2[CH:30]=[CH:31][NH:32][C:33]=2[CH:34]=[CH:35][CH:36]=1)=[O:27])[CH3:24].C([O-])([O-])=O.[K+].[K+]>CN1C(=O)CCC1.[Cu](I)I>[CH2:23]([O:25][C:26]([C:28]1[C:29]2[CH:30]=[CH:31][N:32]([C:2]3[CH:3]=[N:4][CH:5]=[C:6]([C@@H:8]4[CH2:12][CH2:11][CH2:10][N:9]4[C@@H:13]([C:15]4[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=4)[CH3:14])[CH:7]=3)[C:33]=2[CH:34]=[CH:35][CH:36]=1)=[O:27])[CH3:24]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 605034Ethyl indole-4-carboxylateHCID 581118453-Bromo-5-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine

Product 1

HCID 679743931-(5-{(S)-1-[(R)-1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-3-yl)-1H-indole-4-carboxylic acid ethyl esterYield 42.6%

Reagents, catalysts & solvents 2

HCID 83717
Copper iodide
Catalyst
HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
190 °C

Procedure

A mixture of 3-bromo-5-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine (4.0 g, 11 mmol), 1H-indole-4-carboxylic acid ethyl ester (6.3 g, 33 mmol), K2CO3 (2.3 g, 16.6 mmol), copper iodide (0.42 g, 2.2 mmol) in NMP (22 mL) was heated in a microwave tube at 190° C. for 30 minutes. The resulting mixture was cooled to room temperature filtered through celite and concentrated under reduced pressure to give an oil. This oil was purified by silica gel column chromatography (30% ethyl acetate/heptane) to give the titled compound as a yellow solid (2.2 g, 42%).

Workup

  1. temperatureThe resulting mixture was cooled to room temperature
  2. filtrationfiltered through celite and
  3. concentrationconcentrated under reduced pressure
  4. customto give an oil
  5. customThis oil was purified by silica gel column chromatography (30% ethyl acetate/heptane)

Sources & evidence

ORD record
ord-7f13e24fa1d344e0817a7cd5b9bcff6d
Source dataset
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08993523B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes