Methyl iodide → HCID 22597436, compound

HRID 1760205Notes

Reaction equation

HRID 1760205 reaction equation
[H-].[Na+].[ClH:3].[CH3:4][N:5]([CH3:29])[C:6]1[N:14]=[CH:13][N:12]=[C:11]2[C:7]=1[N:8]=[C:9]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=1)[N:10]2[C:15]1[CH:16]=[CH:17][C:18](=[O:21])[NH:19][CH:20]=1.I[CH3:31]>CN(C)C=O.[Cl-].[NH4+].C(OCC)(=O)C>[ClH:3].[CH3:4][N:5]([CH3:29])[C:6]1[N:14]=[CH:13][N:12]=[C:11]2[C:7]=1[N:8]=[C:9]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=1)[N:10]2[C:15]1[CH:16]=[CH:17][C:18](=[O:21])[N:19]([CH3:31])[CH:20]=1

Participants

7

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 22597412HCID 22597412, compound

Product 1

HCID 22597436HCID 22597436, compoundYield 67%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
3 °C

Procedure

60 to 70% sodium hydride (28 mg, 0.700 mmol) was added to a suspension of 5-[6-(dimethylamino)-8-(3-fluorophenyl)-9H-9-purinyl]-1,2-dihydro-2-pyridinonehydrochloride (130 mg, 0.336 mmol) in Example 4 in N,N-dimethylformamide (3 ml), and the mixture was stirred in a nitrogen atmosphere at 0 to 6° C. After 1 hour, iodomethane (23 μl, 0.369 mmol) was added thereto and stirred. After 30 minutes, 60 to 70% sodium hydride (17 mg, 0.425 mmol) was added thereto, and 30 minutes thereafter, additional iodomethane (23 μl, 0.369 mmol) was added thereto and stirred. After 30 minutes, the reaction solution was diluted with a saturated aqueous ammonium chloride solution and ethyl acetate. The organic layer was washed with a saturated aqueous ammonium chloride solution (×1) and then extracted with 1N hydrochloric acid (×1). The 1N hydrochloric acid layer was adjusted to pH 9-10 with IN aqueous sodium hydroxide solution and extracted with ethyl acetate (×1). The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was dissolved in methanol-4N hydrochloric acid/ethyl acetate (1.5 ml) and concentrated. The residue was crystallized from methanol/diethyl ether, and then the solid was collected by filtration and washed with diethyl ether, to give the title compound (90 mg, 67%) as a colorless solid.

Workup

  1. stirringstirred
  2. waitAfter 30 minutes
  3. stirringstirred
  4. waitAfter 30 minutes
  5. washThe organic layer was washed with a saturated aqueous ammonium chloride solution (×1)
  6. extractionextracted with 1N hydrochloric acid (×1)
  7. extractionextracted with ethyl acetate (×1)
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in methanol-4N hydrochloric acid/ethyl acetate (1.5 ml)
  11. concentrationconcentrated
  12. customThe residue was crystallized from methanol/diethyl ether
  13. filtrationthe solid was collected by filtration
  14. washwashed with diethyl ether

Sources & evidence

ORD record
ord-ea0bbb76a2034767842db28641ef9785
Source dataset
uspto-grants-2005_01
Patent number
US06841549B1

Reaction notes

Loading…