8-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indole → (Z)-8-chloro-5-(2-(4-fluorophenyl)prop-1-enyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1401616Notes

Reaction equation

HRID 1401616 reaction equation
Br[CH:2]=[C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)[CH3:4].P([O-])([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O.[Cl:28][C:29]1[CH:37]=[CH:36][C:35]2[NH:34][C:33]3[CH2:38][CH2:39][N:40]([CH3:42])[CH2:41][C:32]=3[C:31]=2[CH:30]=1>CN(C=O)C.[Cu]I>[Cl:28][C:29]1[CH:37]=[CH:36][C:35]2[N:34](/[CH:2]=[C:3](\[C:5]3[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=3)/[CH3:4])[C:33]3[CH2:38][CH2:39][N:40]([CH3:42])[CH2:41][C:32]=3[C:31]=2[CH:30]=1

Participants

7

Reactant 4

HCID 196158-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indoleHCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 86644757(1-Bromoprop-1-en-2-yl)-4-fluorobenzene

Product 1

HCID 46199580(Z)-8-chloro-5-(2-(4-fluorophenyl)prop-1-enyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-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

1-(1-Bromoprop-1-en-2-yl)-4-fluorobenzene (511.2 mg, 2.4 mmol) was dissolved in DMF. Potassium phosphate (848 mg, 4 mmol) was added followed by the addition of copper (I)iodide (38 mg, 0.2 mmol) and L-proline (46 mg, 0.4 mmol). 8-chloro-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole (440 mg, 2 mmol) was added to the reaction mixture and nitrogen gas purged for 2 min. The reaction mixture was heated at 85° C. overnight. The reaction mixture was cooled to RT and ice water was added. Solid mass was filtered under vacuum and crude purified by silica gel chromatography using 0-3% MeOH: DCM as eluent. Two isomers were further purified through reverse phase HPLC and peak 1 was submitted as the final compound. Yield: 120 mg. 1H NMR (DMSO, HCl salt) δ (ppm): 7.50 (s, 1H), 7.10-6.95 (m, 6H), 6.82 (s, 1H), 4.50 (m, 1H), 4.20 (m, 1H), 3.60 (m, 2H), 2.85 (s, 3H), 2.80 (m, 2H), 2.25 (s, 3H).

Workup

  1. custompurged for 2 min
  2. temperatureThe reaction mixture was cooled to RT
  3. additionice water was added
  4. filtrationSolid mass was filtered under vacuum and crude
  5. custompurified by silica gel chromatography
  6. customTwo isomers were further purified through reverse phase HPLC and peak 1

Sources & evidence

ORD record
ord-9d47d82c25594bd9b0e4ffc5739bb69b
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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