Potassium Phosphate, Tribasic → (E)-2-methyl-5-(2-(pyridin-4-yl)prop-1-enyl)-8-(trifluoromethoxy)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1401544Notes

Reaction equation

HRID 1401544 reaction equation
[CH3:1][N:2]1[CH2:19][CH2:18][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([O:13][C:14]([F:17])([F:16])[F:15])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.N1CCC[C@H]1C(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH:37]=[C:38]([C:40]1[CH:45]=[CH:44][N:43]=[CH:42][CH:41]=1)[CH3:39]>CN(C=O)C.[Cu]I>[CH3:1][N:2]1[CH2:19][CH2:18][C:5]2[N:6](/[CH:37]=[C:38](/[C:40]3[CH:45]=[CH:44][N:43]=[CH:42][CH:41]=3)\[CH3:39])[C:7]3[CH:8]=[CH:9][C:10]([O:13][C:14]([F:17])([F:15])[F:16])=[CH:11][C:12]=3[C:4]=2[CH2:3]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 594549332-methyl-8-trifluoromethoxy-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleHCID 86642478(E)-4-(1-bromoprop-1-en-2-yl)pyridine

Product 1

HCID 59455249(E)-2-methyl-5-(2-(pyridin-4-yl)prop-1-enyl)-8-(trifluoromethoxy)-2,3,4,5-tetrahydro-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

2-Methyl-8-(trifluoromethoxy)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (135 mg, 0.5 mmol) was dissolved in DMF. Copper (I) iodide (9.5 mg, 0.05 mmol), L-proline (11.5 mg, 0.1 mmol) and potassium phosphate (414 mg, 2 mmol) were added and the reaction mixture was stirred for 10 min. at RT. 4-(1-Bromoprop-1-en-2-yl)pyridine (116 mg, 0.55 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated overnight at 90° 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 0-7% MeOH-DCM. Yield: 12 mg. 1H NMR (CD3OD, TFA salt) δ (ppm): 8.82 (d, 2H), 8.30 (d, 2H), 7.78 (s, 1H), 7.50 (s, 1H), 7.38 (d, 1H), 7.22 (d, 1H), 4.70 (m, 1H), 4.40 (m, 1H), 3.90 (m, 1H), 3.60 (m, 1H), 3.20 (m, 2H), 3.10 (s, 3H), 2.10 (s, 3H).

Workup

  1. customthe reaction mixture was purged with nitrogen
  2. temperatureThe reaction mixture was heated overnight at 90° 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 0-7% MeOH-DCM

Sources & evidence

ORD record
ord-a66041640bb24254b33e92b550c6b49c
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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