Methyl iodide → HCID 9949620, compound

HRID 1760204Notes

Reaction equation

HRID 1760204 reaction equation
C[O:2][CH:3](OC)[N:4]([CH3:6])[CH3:5].[NH2:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[N:12]=[C:13]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=1)[N:14]2[C:19]1[CH:20]=[CH:21]C(=O)NC=1.[H-].[Na+].IC.O.N>CN(C)C=O.[Cl-].[NH4+].C(OCC)(=O)C>[NH2:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[N:12]=[C:13]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=1)[N:14]2[C:19]1[CH:20]=[CH:21][C:3](=[O:2])[N:4]([CH3:6])[CH:5]=1

Participants

9

Reactant 5

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 78373Dimethylformamide dimethyl acetal2×HCID 12136906HCID 12136906, compoundHCID 12896473Azane;hydrate

Product 1

HCID 9949620HCID 9949620, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

N,N-Dimethylformamide dimethylacetal (0.5 ml, 3.76 mmol) was added to a suspension of 5-[6-amino-8-(3-fluorophenyl)-9H-9-purinyl]-1,2-dihydro-2-pyridinone (1.0 g, 3.10 mmol) in Example 2 in N,N-dimethylformamide (10 ml) and stirred in a nitrogen atmosphere at room temperature. After 1 hour, N,N-dimethylformamide dimethyl acetal (0.5 ml, 3.76 mmol) was further added thereto and stirred for additionall 5 hours. The reaction solution was ice-cooled, and 60 to 70% sodium hydride (136 mg, 3.40 mmol) was added thereto at 0 to 6° C. and stirred. After 30 minutes, iodomethane (0.29 ml, 4.66 mmol) was added dropwise thereto and stirred. After 20 minutes, conc. ammonia water (10 ml) was added thereto and stirred at room temperature. After 16 hours, the reaction solution was diluted with a saturated aqueous ammonium chloride solution and ethyl acetate. The aqueous layer was extracted with ethyl acetate (×4), and the combined organic layers were washed with 1 N aqueous sodium hydroxide solution (×1) and a saturated aqueous ammonium chloride solution (×1), dried over anhydrous sodium sulfate and concentrated. The residue was suspended in ethyl acetate, and the solid was collected by filtration and washed with ethyl acetate, to give the title compound in free form (703 mg). This free compound was dissolved in methanol-4N hydrochloric acid/ethyl acetate (1.5 ml) and concentrated. The residue was crystallized from methanol/ethyl acetate/diethyl ether, and the solid was collected by filtration and washed with diethyl ether, to give the title compound (697 mg, 60%) as a colorless solid.

Workup

  1. stirringstirred for additionall 5 hours
  2. temperaturecooled
  3. stirringat 0 to 6° C. and stirred
  4. waitAfter 30 minutes
  5. stirringstirred
  6. waitAfter 20 minutes
  7. stirringstirred at room temperature
  8. waitAfter 16 hours
  9. extractionThe aqueous layer was extracted with ethyl acetate (×4)
  10. washthe combined organic layers were washed with 1 N aqueous sodium hydroxide solution (×1)
  11. dry with materiala saturated aqueous ammonium chloride solution (×1), dried over anhydrous sodium sulfate
  12. concentrationconcentrated
  13. filtrationthe solid was collected by filtration
  14. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-b9d6acef2c4e49ef9f323858dfe557df
Source dataset
uspto-grants-2005_01
Patent number
US06841549B1

Reaction notes

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