Potassium Phosphate, Tribasic → 6-chloro-9-(2-(3,4-difluorophenyl)prop-1-enyl)-2-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole

HRID 1775968Notes

Reaction equation

HRID 1775968 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]1[CH2:11][N:12]([CH3:15])[CH2:13][CH2:14][C:5]2=1.N1CCC[C@H]1C(O)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[CH:33]=[C:34]([C:36]1[CH:41]=[CH:40][C:39]([F:42])=[C:38]([F:43])[CH:37]=1)[CH3:35]>CN(C=O)C.[Cu]I>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:33]=[C:34]([C:36]1[CH:41]=[CH:40][C:39]([F:42])=[C:38]([F:43])[CH:37]=1)[CH3:35])[C:6]1[CH2:11][N:12]([CH3:15])[CH2:13][CH2:14][C:5]2=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 15508373HCID 15508373, compoundHCID 866355044-(1-Bromoprop-1-en-2-yl)-1,2-difluorobenzene

Product 1

HCID 669116566-chloro-9-(2-(3,4-difluorophenyl)prop-1-enyl)-2-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoleYield 46%

Reagents, catalysts & solvents 2

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

Procedure

6-chloro-2-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (79 mg, 0.35 mmol) was dissolved in DMF (6 mL). To this solution was added CuI (8 mg, 0.035 mmol), L-proline (9 mg, 0.086 mmol), K3PO4 (183 mg, 0.862 mmol). The reaction mixture was stirred for 10 min at room temperature followed by addition of 4-(1-bromoprop-1-en-2-yl)-1,2-difluorobenzene (100 mg, 0.431 mmol). The reaction mixture was heated at 80° C. overnight. Solvent was evaporated under reduced pressure, the residue was diluted with brine and extracted with ethyl acetate. Organic layer was dried over Na2SO4, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography to obtain 60 mg of 6-chloro-9-(2-(3,4-difluorophenyl)prop-1-enyl)-2-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole. 1H NMR (DMSO) OXALATE SALT 7.80 (m, 1H), 7.60 (s, 1H), 7.50 (m, 2H), 7.25 (d, 1H), 7.15 (s, 2H), 4.10 (m, 2H), 3.30 (m, 2H), 2.95 (m, 2H), 2.78 (s, 3H), 1.82 (s, 3H).

Workup

  1. temperatureThe reaction mixture was heated at 80° C. overnight
  2. customSolvent was evaporated under reduced pressure
  3. additionthe residue was diluted with brine
  4. extractionextracted with ethyl acetate
  5. dry with materialOrganic layer was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-f60f4d8946ae461e854ed6dd3d96ede4
Source dataset
uspto-grants-2016_02
Patent number
US09260429B2

Reaction notes

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