Piperidine → N2-Butyl-8-(methyloxy)-9-[4-(1-piperidinyl)butyl]-9H-purine-2,6-diamine

HRID 590446Notes

Reaction equation

HRID 590446 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([NH:12][C:13]1[NH:21][C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[N: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.[NH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1.C(N(CC)CC)C>CN(C=O)C>[CH2:8]([NH: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][N:37]2[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11]

Participants

7

Reactant 5

HCID 8082PiperidineHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 813641-Bromo-4-chlorobutaneHCID 178448877HCID 178448877, compound

Product 1

HCID 59252620N2-Butyl-8-(methyloxy)-9-[4-(1-piperidinyl)butyl]-9H-purine-2,6-diamineYield 51.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

N2-Butyl-8-(methyloxy)-3H-purine-2,6-diamine trifluoroacetate (192 mg, 0.547 mmol) and potassium carbonate (189 mg, 1.368 mmol) were suspended in DMF (3 ml) and heated to 60° C. for 1 hour. The reaction mixture was cooled to room temperature, 1-bromo-4-chlorobutane (0.063 ml, 0.547 mmol) added and the reaction stirred for a further 18 hours. Piperidine (0.054 ml, 0.547 mmol) and triethylamine (0.076 ml, 0.547 mmol) were added and the reaction mixture heated to 60° C. for 72 hours. The solvent was removed in vacuo and the residue partitioned between DCM (2 ml) and water (2 ml). The aqueous phase was re-extracted with DCM (2 ml) and the combined organic extracts were concentrated. The residue (ca. 200 mg) was dissolved in 1:1 MeOH:DMSO (1 ml) and purified by MDAP (Method A). The product containing fractions were evaporated in vacuo to give the impure title compound as a yellow gum (106 mg) which was used without further purification.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. temperaturethe reaction mixture heated to 60° C. for 72 hours
  3. customThe solvent was removed in vacuo
  4. customthe residue partitioned between DCM (2 ml) and water (2 ml)
  5. extractionThe aqueous phase was re-extracted with DCM (2 ml)
  6. concentrationthe combined organic extracts were concentrated
  7. dissolutionThe residue (ca. 200 mg) was dissolved in 1:1 MeOH
  8. customDMSO (1 ml) and purified by MDAP (Method A)
  9. additionThe product containing fractions
  10. customwere evaporated in vacuo

Sources & evidence

ORD record
ord-c381a789cd864ce1abfaa222d43aff2b
Source dataset
uspto-grants-2016_01
Patent number
US09233962B2

Reaction notes

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