Potassium Phosphate, Tribasic → HCID 59454973, compound

HRID 1401522Notes

Reaction equation

HRID 1401522 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][CH:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][CH:5]3[C:4]=2[CH:3]=1.N1CCC[C@H]1C(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH:33]=[C:34]([C:36]1[CH:41]=[C:40]([F:42])[C:39]([F:43])=[CH:38][C:37]=1[Cl:44])[CH3:35]>CN(C=O)C.[Cu]I>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:33]=[C:34](\[C:36]3[CH:41]=[C:40]([F:42])[C:39]([F:43])=[CH:38][C:37]=3[Cl:44])/[CH3:35])[C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 123596228-Chloro-2,3,4,4a,5,9b-hexahydro-2-methyl-1H-pyrido[4,3-b]indoleHCID 86644755HCID 86644755, compound

Product 1

HCID 59454973HCID 59454973, compound

Reagents, catalysts & solvents 2

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

Procedure

8-Chloro-2-methyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole (220 mg, 1 mmol) was dissolved in DMF. Copper (I) iodide (19 mg, 0.1 mmol), L-proline (23, 0.2 mmol) and potassium phosphate (424 mg, 2 mmol) were added and the reaction mixture was stirred for 10 min. at RT. 1-(1-Bromoprop-1-en-2-yl)-2-chloro-4,5-difluorobenzene (321 mg, 1.2 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated overnight at 85° 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 0-5% MeOH-DCM. The product was further purified by HPLC. Yield: 30 mg as the TFA salt. 1H NMR (CD3OD, TFA salt) δ (ppm): 7.40 (d, 1H), 7.30 (m, 1H), 7.22 (d, 1H), 7.15 (t, 1H), 7.08 (d, 1H), 6.90 (s, 1H), 4.40 (m, 2H), 3.60 (m, 2H), 3.10 (m, 2H), 3.05 (s, 3H), 2.30 (s, 3H).

Workup

  1. customthe reaction mixture was purged with nitrogen
  2. temperatureThe reaction mixture was heated overnight at 85° 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 0-5% MeOH-DCM
  9. customThe product was further purified by HPLC

Sources & evidence

ORD record
ord-1bdc99dac7d64fd18458ec9553c37625
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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