Methyl iodide → HCID 57411800, compound

HRID 2046200Notes

Reaction equation

HRID 2046200 reaction equation
[H-].[Na+].[O:3]([CH2:10][C:11]1[CH:20]=[C:14]2[C:15](=[O:19])[NH:16][CH2:17][CH2:18][N:13]2[N:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.I[CH3:22].[NH4+].[Cl-]>CN(C=O)C>[CH3:22][N:16]1[CH2:17][CH2:18][N:13]2[N:12]=[C:11]([CH2:10][O:3][C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:20]=[C:14]2[C:15]1=[O:19]

Participants

6

Reactant 4

HCID 6328Methyl iodide2×HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 57411799HCID 57411799, compound

Product 1

HCID 57411800HCID 57411800, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A 60% dispersion of sodium hydride in mineral oils (9 mg, 0.22 mmol) was added to a stirred solution of 2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (0.05 g, 0.20 mmol) in DMF (3 mL) at 0° C. The mixture was stirred at 0° C. for 15 minutes. Then iodomethane (15 μL, 0.24 mmol) was added at 0° C., the mixture stirred at 0° C. for 1 hour and allowed to warm to room temperature. Then additional iodomethane (15 μL, 0.24 mmol) was added and the mixture was stirred at room temperature overnight. The mixture was treated with a saturated solution of NH4Cl and the solvents evaporated in vacuo. The crude product was diluted with H2O and extracted with DCM. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 40/60). The desired fractions were collected and the solvents evaporated in vacuo to yield 5-methyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (49 mg, 97% yield) as an oil which solidified upon standing. 1H NMR (500 MHz, CDCl3) δ ppm 3.14 (s, 3H), 3.69-3.83 (m, 2H), 4.32-4.49 (m, 2H), 5.09 (s, 2H), 6.93 (s, 1H), 6.96 (t, J=7.2 Hz, 1H), 6.99 (d, J=8.1 Hz, 2H), 7.27-7.32 (m, 2H).

Workup

  1. stirringthe mixture stirred at 0° C. for 1 hour
  2. temperatureto warm to room temperature
  3. stirringthe mixture was stirred at room temperature overnight
  4. customthe solvents evaporated in vacuo
  5. additionThe crude product was diluted with H2O
  6. extractionextracted with DCM
  7. customThe organic layer was separated
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customthe solvents evaporated in vacuo
  11. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 40/60)
  12. customThe desired fractions were collected
  13. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-22e2cdcbeba34a3596875c6d51d3a8b8
Source dataset
uspto-grants-2013_11
Patent number
US08592422B2

Reaction notes

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