Potassium Phosphate, Tribasic → (Z)-9-chloro-6-(2-(2-chlorophenyl)prop-1-enyl)-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole

HRID 1045602Notes

Reaction equation

HRID 1045602 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH3:16])[CH2:14][CH2:15][C:5]=3[C:4]=2[CH:3]=1.Br[CH:18]=[C:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[Cl:27])[CH3:20].N1CCC[C@H]1C(O)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.[Cu]I>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:18]=[C:19](\[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[Cl:27])/[CH3:20])[C:6]3[CH2:11][CH2:12][N:13]([CH3:16])[CH2:14][CH2:15][C:5]=3[C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 685585079-Chloro-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indoleHCID 866424771-(1-Bromoprop-1-en-2-yl)-2-chlorobenzene

Product 1

HCID 59368261(Z)-9-chloro-6-(2-(2-chlorophenyl)prop-1-enyl)-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole

Reagents, catalysts & solvents 2

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

Conditions

Temperature
85 °C

Procedure

9-Chloro-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (234.72 mg, 1 mmol), 1-(1-bromoprop-1-en-2-yl)-2-chlorobenzene (277.82 mg, 1.2 mmol), L-proline (0.2 mmol), CuI (19 mg, 0.1 mmol) and potassium phosphate tribasic (424 mg, 2 mmol) in DMF was stirred at RT and purged with nitrogen. The reaction mixture was heated at 85° C. overnight. An additional 1 eq. of reagents was added and the mixture heated for an additional 24 h. The DMF was evaporated and the residue was poured into water. The precipitate obtained was filtered and purified by silica gel chromatography (100-200-mesh) using 0-5% MeOH:DCM as eluant followed by reverse phase HPLC to separate the isomers. 1HNMR (CDCl3, TFA salt) δ (ppm): 7.34 (m, 2H), 7.24 (d, 1H), 7.12 (d, 2H), 6.95 (m, 1H), 6.70 (m, 2H), 3.60 (m, 1H), 3.50 (m, 1H), 3.25 (m, 2H), 3.10 (m, 2H), 3.0 (m, 2H), 2.80 (s, 3H), 2.34 (s, 3H)

Workup

  1. custompurged with nitrogen
  2. temperaturethe mixture heated for an additional 24 h
  3. customThe DMF was evaporated
  4. additionthe residue was poured into water
  5. customThe precipitate obtained
  6. filtrationwas filtered
  7. custompurified by silica gel chromatography (100-200-mesh)
  8. customto separate the isomers

Sources & evidence

ORD record
ord-f36f7f92decf49249fac585b2eadf3d8
Source dataset
uspto-grants-2013_10
Patent number
US08569287B2

Reaction notes

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