Sodium hydride → methyl 4-{[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidin-2-yl]methyl}benzoate

HRID 1925937Notes

Reaction equation

HRID 1925937 reaction equation
[CH3:1][S:2][C:3]1[C:4]2[NH:11][N:10]=[CH:9][C:5]=2[N:6]=[CH:7][N:8]=1.[H-].[Na+].Br[CH2:15][C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=1>CN(C)C=O.C(OCC)(=O)C>[CH3:1][S:2][C:3]1[C:4]2[N:11]([CH2:15][C:16]3[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=3)[N:10]=[CH:9][C:5]=2[N:6]=[CH:7][N:8]=1.[CH3:1][S:2][C:3]1[C:4]2[C:5](=[CH:9][N:10]([CH2:15][C:16]3[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=3)[N:11]=2)[N:6]=[CH:7][N:8]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 256687Methyl 4-(bromomethyl)benzoateHCID 552958947-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine

Product 2

HCID 67520953methyl 4-{[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidin-2-yl]methyl}benzoateHCID 67521447methyl 4-{[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidin-1-yl]methyl}benzoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine (400 mg) in N,N-dimethylformamide (8 mL) was added 60% sodium hydride (98 mg) under ice-cooling, and the mixture was stirred at room temperature for 10 min. Then, methyl 4-(bromomethyl)benzoate (606 mg) was added under ice-cooling, and the mixture was stirred at room temperature for 30 min. After the completion of the reaction, the mixture was diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate and saturated brine. The organic layer was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (hexane:ethyl acetate=2:1→1:2) to give methyl 4-{[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidin-1-yl]methyl}benzoate (251 mg) and methyl 4-{[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidin-2-yl]methyl}benzoate (450 mg) both as pale-yellow solids.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringthe mixture was stirred at room temperature for 30 min
  4. customAfter the completion of the reaction
  5. washwashed with saturated aqueous sodium hydrogen carbonate and saturated brine
  6. concentrationThe organic layer was concentrated under reduced pressure

Sources & evidence

ORD record
ord-df6d047fa941406cb31f975ff4fc4287
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

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