Dichloromethane → 5-(Pyrid-3-yl)-3-(1-Methylpiperidin-4-yl)-1H-Indole

HRID 278015Notes

Reaction equation

HRID 278015 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14](B(O)O)[CH:15]=3)[NH:10][CH:9]=2)[CH2:4][CH2:3]1.Br[C:21]1[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.C(OCC)(=O)C.[OH-].[Na+]>[N:23]1[CH:24]=[CH:25][CH:26]=[C:21]([C:14]2[CH:15]=[C:16]3[C:11](=[CH:12][CH:13]=2)[NH:10][CH:9]=[C:8]3[CH:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)[CH:22]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 122863-BromopyridineHCID 120418133-(1-Methylpiperidin-4-yl)-1H-Indole-5-Boronic Acid

Product 1

HCID 99041215-(Pyrid-3-yl)-3-(1-Methylpiperidin-4-yl)-1H-IndoleYield 53%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of 3-(1-methylpiperidin-4-yl)-1H-indole-5-boronic acid (0.200g, 0.78 mmol), 3-bromopyridine (0.117 g, 0.74 mmol), 1,1′-[bis(diphenylphosphino)ferrocene]-dichloropalladium(II) complex with dichloromethane (Pd(dppf)Cl2.CH2Cl2) (0.03 g, 0.37 mmol), and 2M aqueous sodium carbonate solution (2 mL) in 7 mL of tetrahydrofuran was heated at reflux, with stirring, overnight. The mixture was allowed to cool to room temperature, diluted with ethyl acetate and 2N aqueous sodium hydroxide solution, and the organic phase was separated, washed with brine solution, dried over sodium sulfate, concentrated in vacuo and purified by silica gel (flash) chromatography (solvent gradient: 100% dichloromethane—25:2 dichloromethane: methanol/aqueous ammonium hydroxide) to give 0.114 g (53%) of the title compound as an amorphous pink solid. FDMS m/e=291 (M+). EA calculated for C19H21N3: C, 78.32; H, 7.26; N, 14.42. Found: C, 78.39; H, 7.39; N, 14.36.

Workup

  1. temperaturewas heated
  2. temperatureat reflux
  3. customthe organic phase was separated
  4. washwashed with brine solution
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel (flash) chromatography (solvent gradient: 100% dichloromethane—25:2 dichloromethane: methanol/aqueous ammonium hydroxide)

Sources & evidence

ORD record
ord-9a97e1b955034872b61dd8386705cd20
Source dataset
uspto-grants-2002_03
Patent number
US06358972B1

Reaction notes

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