Potassium Phosphate, Tribasic → (E)-7,8-dichloro-5-(2-(4-fluorophenyl)prop-1-enyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1401531Notes

Reaction equation

HRID 1401531 reaction equation
[Cl:1][C:2]1[C:3]([Cl:16])=[CH:4][C:5]2[C:6]3[CH2:14][N:13]([CH3:15])[CH2:12][CH2:11][C:7]=3[NH:8][C:9]=2[CH:10]=1.N1CCC[C@H:18]1C(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH:34]=[CH:35][C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1>CN(C=O)C.[Cu]I>[Cl:1][C:2]1[C:3]([Cl:16])=[CH:4][C:5]2[C:6]3[CH2:14][N:13]([CH3:15])[CH2:12][CH2:11][C:7]=3[N:8](/[CH:34]=[C:35](/[C:36]3[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=3)\[CH3:18])[C:9]=2[CH:10]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 538551491-(-2-Bromovinyl)-4-fluorobenzeneHCID 673100727,8-Dichloro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 59454951(E)-7,8-dichloro-5-(2-(4-fluorophenyl)prop-1-enyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

7,8-Dichloro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (900 mg, 3.54 mmol) was dissolved in DMF (5 mL). Copper (I) iodide (66 mg, 0.354 mmol), L-proline (81 mg, 0.69 mmol) and potassium phosphate (1.5 g, 7.08 mmol) were added and the reaction mixture was stirred for 10 min. at RT. 1-(2-Bromovinyl)-4-fluorobenzene (900 mg, 4.23 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated overnight at 80° C. (prolonged heating in some cases was required). DMF was evaporated under reduced pressure, the residue was diluted with water and the solid was filtered. The solid material was purified by silica gel chromatography (100-200 mesh) eluting with 0-10% MeOH-DCM. The product was further purified by HPLC.

Workup

  1. customthe reaction mixture was purged with nitrogen
  2. temperatureThe reaction mixture was heated overnight at 80° C. (
  3. temperatureprolonged heating in some cases
  4. customDMF was evaporated under reduced pressure
  5. additionthe residue was diluted with water
  6. filtrationthe solid was filtered
  7. customThe solid material was purified by silica gel chromatography (100-200 mesh)
  8. washeluting with 0-10% MeOH-DCM
  9. customThe product was further purified by HPLC

Sources & evidence

ORD record
ord-199b4c5025404a47bf0950a79e297883
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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