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 880609Notes

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]

Participants

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

temperatureThe resulting mixture was cooled to room temperature
filtrationfiltered through celite and
concentrationconcentrated under reduced pressure
customto give an oil
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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