8-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indole → HCID 59455016, compound

HRID 1401489Notes

Reaction equation

HRID 1401489 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][CH:31]=[CH:30][C:29]=1[F:34])[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][CH:31]=[CH:30][C:29]=3[F:34])/[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 86642476HCID 86642476, compound

Product 1

HCID 59455016HCID 59455016, compound

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 (200 mg, 1 mmol) was dissolved in DMF (5 mL), Copper (I) iodide (19 mg, 0.1 mmol) L-proline (23 mg, 0.2 mmol) and potassium phosphate (424 mg, 2 mmol) were added and the reaction mixture was stirred for 10 min. at RT. 1-(1-Bromoprop-1-en-2-yl)-2-fluorobenzene (260 mg, 1.2 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated overnight at 85° 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 0-1% MeOH-DCM. The product was further purified by HPLC. Yield: 10 mg. 1H NMR (CDCl3, TFA salt) δ (ppm): 7.25 (s, 1H), 7.10 (m, 3H), 6.90 (m, 2H), 6.82 (m, 1H), 6.70 (s, 1H), 4.62 (d, 1H), 4.0 (d, 1H), 3.70 (m, 1H), 3.20 (m, 1H), 2.92 (m, 1H), 2.82 (s, 3H), 2.70 (m, 1H), 2.0 (s, 3H).

Workup

  1. customthe reaction mixture was purged with nitrogen
  2. temperatureThe reaction mixture was heated overnight at 85° 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 0-1% MeOH-DCM
  9. customThe product was further purified by HPLC

Sources & evidence

ORD record
ord-21d999bf25bf4dffb001ea74eec6ae7d
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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