Oxalic Acid → (E)-5-(2-(4-fluorophenyl)prop-1-enyl)-2-methyl-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1401548Notes

Reaction equation

HRID 1401548 reaction equation
[CH3:1][N:2]1[CH2:18][CH2:17][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([C:13]([F:16])([F:15])[F:14])=[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:36]=[C:37]([C:39]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=1)[CH3:38].C(O)(=O)C(O)=O>CN(C=O)C.C1COCC1.[Cu]I>[F:45][C:42]1[CH:43]=[CH:44][C:39](/[C:37](/[CH3:38])=[CH:36]/[N:6]2[C:7]3[CH:8]=[CH:9][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][C:12]=3[C:4]3[CH2:3][N:2]([CH3:1])[CH2:18][CH2:17][C:5]2=3)=[CH:40][CH:41]=1

Participants

9

Reactant 5

HCID 971Oxalic AcidHCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 67311103HCID 67311103, compoundHCID 86644757(1-Bromoprop-1-en-2-yl)-4-fluorobenzene

Product 1

HCID 59455160(E)-5-(2-(4-fluorophenyl)prop-1-enyl)-2-methyl-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Methyl-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (127 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 (212 mg, 1 mmol) were added and the reaction mixture was stirred for 10 min. at RT. 1-(1-Bromoprop-1-en-2-yl)-4-fluorobenzene (118 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 0-3% MeOH-DCM. The free base was converted into oxalate salt by treatment of oxalic acid (1 equiv) in THF. Yield: 65 mg as the oxalate salt. 1H NMR (CD3OD, oxalate salt) δ (ppm): 7.90 (s, 1H), 7.70 (t, 2H), 7.50 (d, 1H), 7.40 (d, 1H), 7.20 (t, 2H), 7.0 (s, 1H), 4.60 (m, 2H), 3.78 (m, 2H), 3.20 (m, 2H), 3.10 (s, 3H), 1.90 (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 0-3% MeOH-DCM

Sources & evidence

ORD record
ord-b9e506ce284249569e73f96bb75b6ee5
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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