Methyl iodide → HCID 86652998, compound

HRID 383563Notes

Reaction equation

HRID 383563 reaction equation
[Br:1][C:2]1[C:3](=[O:19])[NH:4][C:5]2[N:10]([C:11]3[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]=3[F:18])[N:9]=[CH:8][C:6]=2[N:7]=1.[H-].[Li+].I[CH3:23]>COCCOC.CN(C=O)C>[Br:1][C:2]1[N:7]=[C:6]2[CH:8]=[N:9][N:10]([C:11]3[C:12]([F:18])=[CH:13][CH:14]=[CH:15][C:16]=3[F:17])[C:5]2=[N:4][C:3]=1[O:19][CH3:23]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 62714Lithium hydrideHCID 136352699HCID 136352699, compound

Product 1

HCID 86652998HCID 86652998, compoundYield 6.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 5-bromo-1-(2,6-difluorophenyl)-1H-pyrazolo[4,3-b]pyrazin-6(7H)-one (981 mg, 3.0 mmol) in 10 mL of DME and 1 mL of DMF at RT was treated with lithium hydride (119 mg, 15 mmol) in small portions. Iodomethane (0.62 mL, 9.9 mmol) was added 30 min later. The mixture was stirred at RT for 18 h, and poured into an ice cold sat. NH4Cl solution, then extracted twice with EtOAc. The combined EtOAc layes were washed with brine, dried and concentrated. Purification of the crude material on a silical gel column (25-85% EtOAc in Hexanes) provided: (1) 5-bromo-1-(2,6-difluorophenyl)-6-methoxy-1H-pyrazolo[3,4-b]pyrazine (65 mg, 6.4% yield) as an off white crystalline solid. MS (ES+): 341.0/343.0 (M+H)+; and (2) 5-bromo-1-(2,6-difluorophenyl)-7-methyl-1H-pyrazolo[4,3-b]pyrazin-6(7H)-one (616 mg, 60% yield) as an off white amorphous solid. MS (ES+): 341.0/343.0 (M+H)+.

Workup

  1. extractionextracted twice with EtOAc
  2. washThe combined EtOAc layes were washed with brine
  3. customdried
  4. concentrationconcentrated
  5. customPurification of the crude material on a silical gel column (25-85% EtOAc in Hexanes)
  6. customprovided

Sources & evidence

ORD record
ord-f1e5f3a3f47c4f1190252adc072f13a2
Source dataset
uspto-grants-2013_02
Patent number
US08367671B2

Reaction notes

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