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

HRID 880613Notes

Reaction equation

HRID 880613 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:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[NH:30][CH:29]=1)=[O:27])[CH3:24].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CN[C@H]1CCCC[C@@H]1NC>C1(C)C=CC=CC=1.[Cu](I)I>[CH2:23]([O:25][C:26]([C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:30]([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([C@@H:8]3[CH2:12][CH2:11][CH2:10][N:9]3[C@@H:13]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[CH3:14])[CH:7]=2)[CH:29]=1)=[O:27])[CH3:24]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 247965Ethyl Indole-3-carboxylateHCID 13822957(1S,2S)-(+)-N,N'-Dimethylcyclohexane-1,2-diamineHCID 581118453-Bromo-5-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine

Product 1

HCID 867023541-(5-{(S)-1-[(R)-1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-3-yl)-1H-indole-3-carboxylic acid ethyl esterYield 77.4%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a suspension of 3-bromo-5-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine (2.0 g, 5.5 mmol), 1H-Indole-3-carboxylic acid ethyl ester (1.3 g, 6.6 mmol), copper iodide (0.11 g, 0.55 mmol), K3PO4 (2.5 g, 11.6 mmol) in toluene (5 mL) was added (1S,2S)—N1,N2-dimethylcyclohexane-1,2-diamine (0.16 g, 1.1 mmol). After being flushed with N2, the resulting mixture was heated at 110° C. overnight, 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 using 30-50% EtOAc/heptane to give the titled compound as a light yellow foam (2.0 g, 77%).

Workup

  1. customAfter being flushed with N2
  2. temperaturecooled to room temperature
  3. filtrationfiltered through celite and
  4. concentrationconcentrated under reduced pressure
  5. customto give an oil
  6. customThis oil was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ec723c6a2cb6402ebd43409790d7e485
Source dataset
uspto-grants-2015_03
Patent number
US08993523B2

Reaction notes

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