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

HRID 1045611Notes

Reaction equation

HRID 1045611 reaction equation
[CH3:1][N:2]1[CH2:15][CH2:14][CH:13]2[CH:5]([NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:16])=[CH:11][C:12]=32)[CH2:4][CH2:3]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>[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[N:6](/[CH:26]=[C:27](/[C:29]3[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=3)\[CH3:28])[C:5]=2[CH2:4][CH2:3]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 1678573,9-Dimethyl-1,2,3,4,5,5a,6,10b-octahydroazepino[4,5-b]indoleHCID 86642478(E)-4-(1-bromoprop-1-en-2-yl)pyridine

Product 1

HCID 59368294(E)-3,9-dimethyl-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
85 °C

Procedure

3,9-Dimethyl-1,2,3,4,5,5a,6,10b-octahydroazepino[4,5-b]indole (107.5 mg, 0.5 mmol), potassium phosphate tribasic (212 mg, 1 mmol) in DMF and the mixture purged with nitrogen. The reaction mass was heated at 85° C. for 5 min. In another flask was added 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. This mixture was purged with nitrogen and heated at 90° C. for 5 min. The reaction mixtures were combined and heated at 90° C. overnight. The reaction mass 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. ammonia and using 0-2% MeOH:DCM as eluant. The compound was further purified by reverse phase HPLC to obtain the product. 1HNMR (CD3OD, TFA salt) δ (ppm): 8.70 (d, 2H), 8.10 (d, 2H), 7.62 (s, 1H), 7.38 (s, 1H), 7.05 (d, 2H), 3.80 (m, 2H), 3.40 (m, 2H), 3.30 (m, 2H), 3.20 (m, 2H), 3.05 (s, 3H), 2.42 (s, 3H), 2.05 (s, 3H).

Workup

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

Sources & evidence

ORD record
ord-b538be35d250402099ae7f93a7eed243
Source dataset
uspto-grants-2013_10
Patent number
US08569287B2

Reaction notes

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