Potassium Carbonate → 2-(Butyloxy)-9-(4-chlorobutyl)-8-(methyloxy)-9H-purin-6-amine

HRID 590425Notes

Reaction equation

HRID 590425 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[NH:19]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11].C(=O)([O-])[O-].[K+].[K+].Br[CH2:32][CH2:33][CH2:34][CH2:35][Cl:36]>CN(C=O)C>[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[N:19]2[CH2:32][CH2:33][CH2:34][CH2:35][Cl:36])=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 813641-Bromo-4-chlorobutaneHCID 178450370HCID 178450370, compound

Product 1

HCID 592526152-(Butyloxy)-9-(4-chlorobutyl)-8-(methyloxy)-9H-purin-6-amineYield 75.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

2-(Butyloxy)-8-(methyloxy)-9H-purin-6-amine trifluoroacetate (2 g, 5.69 mmol) and potassium carbonate (1.967 g, 14.23 mmol) were suspended in DMF (20 ml) and heated to 50° C., under nitrogen for 30 mins. The mixture was cooled to room temperature, 1-bromo-4-chlorobutane (0.656 ml, 5.69 mmol) was added and stirring continued at room temperature for 20 hours. The solvent was evaporated under reduced pressure and the residue was partitioned between DCM (40 ml) and water (40 ml). The layers were separated using a hydrophobic frit and the aqueous layer washed with DCM (10 ml). The combined organic extracts were concentrated in vacuo to give crude material that was purified by silica chromatography using the FlashMaster (70 g cartridge) eluting with a cyclohexane:ethyl acetate 0-100% gradient over 30 mins. The product-containing fractions were combined and evaporated to give the title compound as a white solid (1.4 g).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customThe solvent was evaporated under reduced pressure
  3. customthe residue was partitioned between DCM (40 ml) and water (40 ml)
  4. customThe layers were separated
  5. washthe aqueous layer washed with DCM (10 ml)
  6. concentrationThe combined organic extracts were concentrated in vacuo
  7. customto give crude material that
  8. customwas purified by silica chromatography
  9. washeluting with a cyclohexane
  10. waitethyl acetate 0-100% gradient over 30 mins
  11. customevaporated

Sources & evidence

ORD record
ord-ecb85ca87e0b48a0856bfde2896c8c8e
Source dataset
uspto-grants-2016_01
Patent number
US09233962B2

Reaction notes

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