Potassium Phosphate, Tribasic → HCID 66911736, compound

HRID 2198368Notes

Reaction equation

HRID 2198368 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]([CH2:16][CH3:17])[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:35]=[C:36]([C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[C:40]([F:46])[CH:39]=1)[CH3:37]>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:35]=[C:36]([C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[C:40]([F:46])[CH:39]=1)[CH3:37])[C:6]1[CH:11]([CH2:16][CH3:17])[N:12]([CH3:15])[CH2:13][CH2:14][C:5]2=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 669117386-chloro-1-ethyl-2-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoleHCID 866355054-(1-Bromoprop-1-en-2-yl)-2-fluoro-1-methoxybenzene

Product 1

HCID 66911736HCID 66911736, compoundYield 15%

Reagents, catalysts & solvents 2

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

Procedure

6-chloro-1-ethyl-2-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (84 mg, 0.34 mmol) was dissolved in DMF (5 mL). To this solution was added CuI (6 mg, 0.034 mmol), L-proline (8 mg, 0.068 mmol), K3PO4 (145 mg, 0.68 mmol). The reaction mixture was stirred for 10 min at room temperature followed by addition of 4-(1-bromoprop-1-en-2-yl)-2-fluoro-1-methoxybenzene (100 mg, 0.408 mmol). The reaction mixture was heated at 80° C. for 18 h. 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 21 mg of 6-chloro-1-ethyl-9-(2-(3-fluoro-4-methoxyphenyl)prop-1-enyl)-2-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole. 1H NMR (CD3OD) TFA SALT 7.60 (d, 1H), 7.42 (m, 2H), 7.20 (m, 3H), 7.0 (s, 1H), 4.60 (m, 1H), 3.90 (s, 3H), 3.8 (m, 1H), 3.60 (m, 1H), 3.20 (m, 2H), 3.05 (s, 3H), 2.10 (m, 2H), 1.90 (s, 3H), 1.10 (t, 3H).

Workup

  1. temperatureThe reaction mixture was heated at 80° C. for 18 h
  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-db70488d9d274900abcd0ce2c93525c5
Source dataset
uspto-grants-2012_12
Patent number
US08338447B2

Reaction notes

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