8-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indole → (E)-8-chloro-5-(2-(3,4-dichlorophenyl)prop-1-enyl)-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole

HRID 1401506Notes

Reaction equation

HRID 1401506 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH:25]=[C:26]([C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([Cl:35])[CH:29]=1)[CH3:27]>CN(C=O)C.[Cu]I>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:25]=[C:26](/[C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([Cl:35])[CH:29]=3)\[CH3:27])[C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 196158-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indoleHCID 62657Potassium Phosphate, TribasicHCID 86635503(1-Bromoprop-1-en-2-yl)-3,4-dichlorobenzene

Product 1

HCID 59455191(E)-8-chloro-5-(2-(3,4-dichlorophenyl)prop-1-enyl)-2,3,4,5-tetrahydro-2-methyl-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

8-Chloro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (69 mg, 0.31 mmol) was dissolved in DMF (5 mL). Copper (I) iodide (6 mg, 0.032 mmol) L-proline (7 mg, 0.063 mmol) and potassium phosphate (134 mg, 0.63 mmol) were added and the reaction mixture was stirred for 10 min. at RT. 4-(1-Bromoprop-1-en-2-yl)-1,2-dichlorobenzene (100 mg, 0.378 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) followed by HPLC. Yield: 13 mg as the TFA salt. 1H NMR (CD3OD, TFA salt) δ (ppm): 7.82 (d, 1H), 7.62 (d, 2H), 7.58 (d, 1H), 7.22 (m, 2H), 7.10 (s, 1H), 4.80 (m, 1H), 4.40 (m, 1H), 3.90 (m, 1H), 3.62 (m, 1H), 3.20 (m, 2H), 3.15 (s, 3H), 1.95 (s, 3H).

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)

Sources & evidence

ORD record
ord-640a3b1c20e44e9dbe9fe5e60d9dfaec
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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