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

HRID 2198350Notes

Reaction equation

HRID 2198350 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]1[CH:11]([CH3:16])[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:34]=[C:35]([C:37]1[CH:42]=[CH:41][C:40]([F:43])=[C:39]([F:44])[CH:38]=1)[CH3:36]>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:34]=[C:35]([C:37]1[CH:42]=[CH:41][C:40]([F:43])=[C:39]([F:44])[CH:38]=1)[CH3:36])[C:6]1[CH:11]([CH3:16])[N:12]([CH3:15])[CH2:13][CH2:14][C:5]2=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 66911739HCID 66911739, compoundHCID 866355044-(1-Bromoprop-1-en-2-yl)-1,2-difluorobenzene

Product 1

HCID 669116526-chloro-9-(2-(3,4-difluorophenyl)prop-1-enyl)-1,2-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoleYield 30.9%

Reagents, catalysts & solvents 2

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

Procedure

6-chloro-1,2-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (84 mg, 0.36 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 43 mg of 6-chloro-9-(2-(3,4-difluorophenyl)prop-1-enyl)-1,2-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole. 1H NMR (CD3OD) OXALATE SALT 7.62 (m, 1H), 7.60 (s, 1H), 7.50 (m, 1H), 7.36 (m, 1H), 7.22 (m, 2H), 7.05 (s, 1H), 4.80 (m, 2H), 3.60 (m, 1H), 3.10 (m, 2H), 3.0 (s, 3H), 1.90 (s, 3H), 1.60 (d, 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-d464e33bc6894f48b5e7b01576c17146
Source dataset
uspto-grants-2012_12
Patent number
US08338447B2

Reaction notes

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