Potassium Phosphate, Tribasic → HCID 59368207, compound

HRID 1045618Notes

Reaction equation

HRID 1045618 reaction equation
[CH3:1][N:2]1[CH2:15][CH2:14][C:13]2[C:12]3[CH:11]=[C:10]([CH3:16])[CH:9]=[CH:8][C:7]=3[NH:6][C:5]=2[CH2:4][CH2:3]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]([Cl:43])=[CH:39][C:38]=1[Cl:44])[CH3:36]>CN(C=O)C.[Cu]I>[Cl:44][C:38]1[CH:39]=[C:40]([Cl:43])[CH:41]=[CH:42][C:37]=1/[C:35](/[CH3:36])=[CH:34]\[N:6]1[C:7]2[CH:8]=[CH:9][C:10]([CH3:16])=[CH:11][C:12]=2[C:13]2[CH2:14][CH2:15][N:2]([CH3:1])[CH2:3][CH2:4][C:5]1=2

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 685600921,2,3,4,5,6-Hexahydro-3,9-dimethylazepino[4,5-b]indoleHCID 86642475HCID 86642475, compound

Product 1

HCID 59368207HCID 59368207, compound

Reagents, catalysts & solvents 2

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

Procedure

3,9-Dimethyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (214 mg, 1 mmol) was dissolved in DMF. Copper (I) iodide (19 mg, 0.1 mmol), L-proline (23 mg, 0.2 mmol) and K3PO4 (424 mg, 2 mmol) were added and the reaction mixture was stirred for 10 min at RT. 1-(1-Bromoprop-1-en-2-yl)-2,4-dichlorobenzene (318 mg, 1.2 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated at 85° C. for overnight (prolonged heating in some cases was required). The 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% methanol-dichloromethane. The product was further purified by reverse phase HPLC. Yield: 30 mg. 1HNMR (CDCl3, TFA salt) δ (ppm): 7.50 (s, 1H), 7.38 (s, 2H), 7.28 (d, 1H), 7.18 (d, 1H), 7.05 (d, 1H), 6.56 (s, 1H), 3.90 (m, 2H), 3.40 (m, 1H), 3.22 (m, 5H), 3.0 (s, 3H), 2.42 (s, 3H), 1.82 (s, 3H)

Workup

  1. customthe reaction mixture was purged with nitrogen
  2. temperatureThe reaction mixture was heated at 85° C. for overnight (
  3. temperatureprolonged heating in some cases
  4. customThe DMF 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% methanol-dichloromethane
  9. customThe product was further purified by reverse phase HPLC

Sources & evidence

ORD record
ord-1332dc9d42314bb98b59469c2cc7135c
Source dataset
uspto-grants-2013_10
Patent number
US08569287B2

Reaction notes

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