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

HRID 1045606Notes

Reaction equation

HRID 1045606 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.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[CH:26]=[C:27]([C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1)[CH3:28].N1CCC[C@H]1C(O)=O>CN(C=O)C.[Cu]I.O>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:26]=[C:27](/[C:29]3[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=3)\[CH3:28])[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

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 685585079-Chloro-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indoleHCID 86642478(E)-4-(1-bromoprop-1-en-2-yl)pyridine

Product 1

HCID 59368258(E)-9-chloro-3-methyl-6-(2-(pyridin-4-yl)prop-1-enyl)-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
90 °C

Procedure

A mixture of 9-chloro-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (117 mg, 0.5 mmol) and potassium phosphate tribasic (212 mg, 1 mmol) in DMF was purged with nitrogen and heated at 90° C. 4-(1-Bromoprop-1-en-2-yl)pyridine (107.83 mg, 0.55 mmol), L-proline (11.5 mg, 0.1 mmol), CuI (9.5 mg, 0.05 mmol) in DMF were charged in a separate flask. This mixture was purged with nitrogen and heated at 90° C. for 5 min. Both reaction mixtures were combined and heated at 90° C. overnight. The reaction mixture was poured into water to obtain a precipitate. The precipitate was filtered and purified with silica column chromatography (100-200 mesh) by neutralizing the silica gel with 2-3 drops of aq. NH3 and using 0-2% MeOH:DCM as eluant. Compound was further purified by reverse phase HPLC to obtain the product. 1HNMR (CD3OD, TFA salt) δ (ppm): 8.80 (d, 2H), 8.20 (d, 2H), 7.70 (d, 1H), 7.58 (d, 1H), 7.20 (s, 2H), 3.70 (m, 2H), 3.40 (m, 2H), 3.30 (m, 4H), 3.05 (s, 3H), 2.02 (s, 3H).

Workup

  1. customwas purged with nitrogen
  2. customThis mixture was purged with nitrogen
  3. temperatureheated at 90° C. for 5 min
  4. customBoth reaction mixtures
  5. temperatureheated at 90° C. overnight
  6. customto obtain a precipitate
  7. filtrationThe precipitate was filtered
  8. custompurified with silica column chromatography (100-200 mesh)
  9. customCompound was further purified by reverse phase HPLC
  10. customto obtain the product

Sources & evidence

ORD record
ord-3e8cbc4f77674c2d8e8d801b0fd0512c
Source dataset
uspto-grants-2013_10
Patent number
US08569287B2

Reaction notes

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