1,3-Dibromopropane → 9-[3-(1-Azetidinyl)propyl]-2-(butyloxy)-8-(methyloxy)-9H-purin-6-amine

HRID 1616267Notes

Reaction equation

HRID 1616267 reaction equation
F[C:2](F)(F)[C:3](O)=O.[CH2:8]([O:12][C:13]1[NH:14][C:15]([NH2:24])=[C:16]2[C:20]([N:21]=1)=[N:19][C:18]([O:22][CH3:23])=[N:17]2)[CH2:9][CH2:10][CH3:11].C(=O)([O-])[O-].[K+].[K+].BrCCCBr.N1CCC1.[CH2:40]([N:42]([CH2:45][CH3:46])[CH2:43]C)C>CN(C=O)C>[N:42]1([CH2:40][CH2:2][CH2:3][N:19]2[C:18]([O:22][CH3:23])=[N:17][C:16]3[C:20]2=[N:21][C:13]([O:12][CH2:8][CH2:9][CH2:10][CH3:11])=[N:14][C:15]=3[NH2:24])[CH2:43][CH2:46][CH2:45]1

Participants

7

Reactant 5

HCID 80011,3-DibromopropaneHCID 8471TriethylamineHCID 10422AzetidineHCID 11430Potassium CarbonateHCID 178450357HCID 178450357, compound

Product 1

HCID 592526009-[3-(1-Azetidinyl)propyl]-2-(butyloxy)-8-(methyloxy)-9H-purin-6-amineYield 13.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

2-(Butyloxy)-8-(methyloxy)-1H-purin-6-amine trifluoroacetate (100 mg, 0.285 mmol) was dissolved in DMF (1 ml) and potassium carbonate (98 mg, 0.712 mmol) was added. The reaction mixture was stirred at 50° C. under nitrogen for 1 hour and then cooled to room temperature. 1,3-Dibromopropane (0.029 ml, 0.285 mmol) was added and after stirring for a further 40 mins. azetidine (0.038 ml, 0.569 mmol) and triethylamine (0.079 ml, 0.569 mmol) in DMF (1 ml) were added. The reaction mixture was then stirred for a further 18 hours. The solvent was removed and the residue was partitioned between dichloromethane (2 ml) and water (2 ml). The layers were separated using a hydrophobic frit and the aqueous phase was re-extracted with DCM (2 ml). The combined organic extracts were concentrated and the residue was dissolved in 1:1 MeOH:DMSO (1 ml) and purified by MDAP (Method A). The product containing fractions were evaporated under a stream of nitrogen to give the title compound as a white solid (13 mg).

Workup

  1. temperaturecooled to room temperature
  2. stirringafter stirring for a further 40 mins
  3. stirringThe reaction mixture was then stirred for a further 18 hours
  4. customThe solvent was removed
  5. customthe residue was partitioned between dichloromethane (2 ml) and water (2 ml)
  6. customThe layers were separated
  7. extractionthe aqueous phase was re-extracted with DCM (2 ml)
  8. concentrationThe combined organic extracts were concentrated
  9. dissolutionthe residue was dissolved in 1:1 MeOH
  10. customDMSO (1 ml) and purified by MDAP (Method A)
  11. additionThe product containing fractions
  12. customwere evaporated under a stream of nitrogen

Sources & evidence

ORD record
ord-572a701d4fc54bfba833f8d7e8471867
Source dataset
uspto-grants-2014_07
Patent number
US08765772B2

Reaction notes

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