Methyl iodide → 8-Fluoro-6-(4-fluoro-phenyl)-2-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one

HRID 925681Notes

Reaction equation

HRID 925681 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[C:8]2[N:7]3[CH2:18][CH2:19][NH:20][C:21](=[O:22])[C:6]3=[CH:5][C:4]=2[CH:3]=1.[H-].[Na+].I[CH3:26]>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[C:8]2[N:7]3[CH2:18][CH2:19][N:20]([CH3:26])[C:21](=[O:22])[C:6]3=[CH:5][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 900360598-Fluoro-6-(4-fluoro-phenyl)-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one

Product 1

HCID 900358568-Fluoro-6-(4-fluoro-phenyl)-2-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-oneYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 8-fluoro-6-(4-fluoro-phenyl)-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (example 18) (0.05 g, 0.17 mmol) in DMF (1.1 ml) was added at room temperature sodium hydride (8.78 mg, 0.2 mmol), and the mixture was allowed to stir at room temperature for 30 min. Afterwards iodomethane (23.8 mg, 10.5 μl, 0.17 mmol) was added and the reaction mixture was allowed to stir at room temperature for 16 h. The mixture was poured into ice/water (30 ml) and extracted with ethyl acetate (2×25 ml). The combined organic layers were washed with brine (25 ml), dried (MgSO4) and evaporated. The crude product (50 mg) was further purified by flash chromatography on silica gel [dichloromethane-dichloromethane/MeOH 9:1 (0-50%)] to yield the title compound as a white solid (21 mg, 40%), MS (ISP) m/z=313.4 [(M+H)+], mp 212° C.

Workup

  1. stirringto stir at room temperature for 16 h
  2. extractionextracted with ethyl acetate (2×25 ml)
  3. washThe combined organic layers were washed with brine (25 ml)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe crude product (50 mg) was further purified by flash chromatography on silica gel [dichloromethane-dichloromethane/MeOH 9:1 (0-50%)]

Sources & evidence

ORD record
ord-35211e7b08744a9e9ac3e9c6c338cc13
Source dataset
uspto-grants-2016_03
Patent number
US09284321B2

Reaction notes

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