Isopropanol → 2,6-dichloro-9-(propan-2-yl)-9H-purine

HRID 928154Notes

Reaction equation

HRID 928154 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([Cl:11])[N:3]=1.[CH:12](O)([CH3:14])[CH3:13].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1C=CC(COC(/N=N/C(OCC2C=CC=CC=2)=O)=O)=CC=1>C1COCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:12]([CH3:14])[CH3:13])=[C:4]([Cl:11])[N:3]=1

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 11776TriphenylphosphineHCID 5387121Dibenzyl azodicarboxylateHCID 1784188752,6-dichloro-1H-purine

Product 1

HCID 112184902,6-dichloro-9-(propan-2-yl)-9H-purine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 500 mL round bottom flask was charged with 2,6-dichloro-9H-purine (1.89 g, 10 mmol), isopropanol (3.1 mL, 40 mmol, 4 mol eq), THF (150 mL), and triphenylphosphine (polystyrene-bound, ˜3 mmol/g, 6.7 g, or about 20 mmol load) and the resulting mixture was stirred and cooled in a water bath under nitrogen. A solution of DBAD (4.85 g, 20 mmol) in THF (50 mL) was added dropwise via an addition funnel over 30 min and the resulting reaction mixture stirred at ambient temperature for 20 hr. The resin was removed by filtration and washed well with ethyl acetate. The combined filtrates were evaporated to give a light yellow solid that was purified via flash column chromatography (dry loaded using silica/DCM) with a gradient of 0-50% ethyl acetate in heptanes to give:

Workup

  1. temperaturecooled in a water bath under nitrogen
  2. customthe resulting reaction mixture
  3. stirringstirred at ambient temperature for 20 hr
  4. customThe resin was removed by filtration
  5. washwashed well with ethyl acetate
  6. customThe combined filtrates were evaporated
  7. customto give a light yellow solid
  8. customthat was purified via flash column chromatography (dry loaded using silica/DCM) with a gradient of 0-50% ethyl acetate in heptanes
  9. customto give

Sources & evidence

ORD record
ord-bfe75785b316407a998800d5e4028cb5
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Reaction notes

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