Methyl iodide → 6-Fluoro-2,3,4,5-tetrahydro-5-methyl-2-[(1,5-dimethyl-1H-imidazol-4-yl)methyl]-1H-pyrido[4,3-b]indol-1-one

HRID 2081223Notes

Reaction equation

HRID 2081223 reaction equation
[F:1][C:2]1[C:10]2[N:9]([CH3:11])[C:8]3[CH2:12][CH2:13][N:14]([CH2:17][C:18]4[N:19]=[CH:20][NH:21][C:22]=4[CH3:23])[C:15](=[O:16])[C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:27]>CN(C=O)C.ClCCl>[F:1][C:2]1[C:10]2[N:9]([CH3:11])[C:8]3[CH2:12][CH2:13][N:14]([CH2:17][C:18]4[N:19]=[CH:20][N:21]([CH3:27])[C:22]=4[CH3:23])[C:15](=[O:16])[C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 172999Lurosetron

Product 1

HCID 197992776-Fluoro-2,3,4,5-tetrahydro-5-methyl-2-[(1,5-dimethyl-1H-imidazol-4-yl)methyl]-1H-pyrido[4,3-b]indol-1-oneYield 17.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A stirred solution of 6-fluoro-2,3,4,5-tetrahydro-5-methyl-2-[(5-methyl-1H-imidazol -4-yl)methyl]-1H-pyrido[4,3-b]indol-1-one (347 mg) in dry DMF was treated with sodium hydride (73% dispersion in oil; 49 mg) and stirred under nitrogen for 30 min. The reaction mixture was then cooled to 0° and iodomethane (217 mg) was added dropwise. The reaction mixture was then allowed to warm to room temperature, with stirring being continued for 2 h. DMF was removed in vacuo and the residue was dissolved in dichloromethane (75 ml) and washed with water (3×75 ml) and brine (2×50 ml). The combined aqueous washings were extracted with dichloromethane (2×50 ml) and the combined organic extracts were dried and concentrated in vacuo to give an oil. This was dissolved in dichloromethane and adsorbed onto silica. Purification by FCC eluting with System A (200:10:1) gave a solid which was triturated with ether and then dried in vacuo to give the title compound (62 mg), m.p. 174°-175°.

Workup

  1. temperatureThe reaction mixture was then cooled to 0°
  2. stirringwith stirring
  3. waitbeing continued for 2 h
  4. customDMF was removed in vacuo
  5. dissolutionthe residue was dissolved in dichloromethane (75 ml)
  6. washwashed with water (3×75 ml) and brine (2×50 ml)
  7. extractionThe combined aqueous washings were extracted with dichloromethane (2×50 ml)
  8. customthe combined organic extracts were dried
  9. concentrationconcentrated in vacuo
  10. customto give an oil
  11. customPurification by FCC
  12. washeluting with System A (200:10:1)
  13. customgave a solid which
  14. customwas triturated with ether
  15. customdried in vacuo

Sources & evidence

ORD record
ord-d45fa1f7aa834a7fad86ee97b644c38c
Source dataset
uspto-grants-1993_02
Patent number
US05183820

Reaction notes

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