Dimethylformamide → 7-Benzyl-3-cyclopropylmethylxanthine

HRID 323864Notes

Reaction equation

HRID 323864 reaction equation
Cl.[CH2:2]([N:9]1[C:17]2[C:16](=[O:18])[NH:15]C(N)=NC=2[N:11]=[CH:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[H-].[Na+].[CH:22]1([CH2:25]Br)C[CH2:23]1.[CH3:27][N:28]([CH3:31])[CH:29]=[O:30]>O.CO>[CH2:2]([N:9]1[C:17]2[C:16](=[O:18])[NH:15][C:29](=[O:30])[N:28]([CH2:31][CH:22]3[CH2:25][CH2:23]3)[C:27]=2[N:11]=[CH:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 81503Bromomethylcyclopropane2×HCID 1356820512-Amino-7-benzyl-1,7-dihydro-6H-purin-6-one hydrochloride

Product 1

HCID 220073157-Benzyl-3-cyclopropylmethylxanthine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of 7 g (29.0 mmol) of 7-benzylxanthine from Example 6 b) in 200 ml of dimethylformamide was heated to 50° C. and treated in portions with 0.69 g (29.0) mmol of sodium hydride and stirred at 50° C. for one hour. 2.76 ml (29.0 mmol) of cyclopropylmethyl bromide were added to this suspension and the temperature was increased to 80° C. After 7 hours at 80° C., 1 ml (11.0 mmol) of cyclopropylmethyl bromide was added again. After a further 6 hours, 24 ml of water and 10 ml of methanol were added, and the mixture was allowed to stand overnight, treated again with 120 ml of water and extracted three times using 300 ml of methyl tert-butyl ether each time. The organic phases were washed with water, dried using magnesium sulfate and concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica gel column, dichloromethane/methanol (99/1).

Workup

  1. temperaturethe temperature was increased to 80° C
  2. waitAfter 7 hours at 80° C.
  3. waitAfter a further 6 hours
  4. waitto stand overnight
  5. extractionextracted three times
  6. washThe organic phases were washed with water
  7. customdried
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by flash chromatography on a silica gel column, dichloromethane/methanol (99/1)

Sources & evidence

ORD record
ord-e101a7038ae74029b088eb3d222d92bc
Source dataset
uspto-grants-2001_04
Patent number
US06214992B1

Reaction notes

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