Azepane → N2-Butyl-9-[4-(hexahydro-1H-azepin-1-yl)butyl]-8-(methyloxy)-9H-purine-2,6-diamine

HRID 1616280Notes

Reaction equation

HRID 1616280 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[CH2:43][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[CH2:43][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 8119AzepaneHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 813641-Bromo-4-chlorobutaneHCID 178448877HCID 178448877, compound

Product 1

HCID 59252652N2-Butyl-9-[4-(hexahydro-1H-azepin-1-yl)butyl]-8-(methyloxy)-9H-purine-2,6-diamineYield 6.1%

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) was added and the reaction stirred for a further 18 hours. Hexahydro-1H-azepine (54.2 mg, 0.547 mmol) and triethylamine (0.076 ml, 0.547 mmol) were added and the reaction mixture heated to 60° C. for 18 hours. The solvent was removed in vacuo and the residue was partitioned between DCM (5 ml) and water (5 ml). The aqueous phase was re-extracted with DCM (5 ml) and the combined organic extracts were concentrated in vacuo. The residue was dissolved in 1:1 MeOH:DMSO (2 ml) and purified in 2 injections by MDAP (Method B). This provided material (74 mg) that was still impure and which was repurified by MDAP (Method A). The product containing fractions were evaporated under a stream of nitrogen to give the title compound as a clear gum (13 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. temperaturethe reaction mixture heated to 60° C. for 18 hours
  3. customThe solvent was removed in vacuo
  4. customthe residue was partitioned between DCM (5 ml) and water (5 ml)
  5. extractionThe aqueous phase was re-extracted with DCM (5 ml)
  6. concentrationthe combined organic extracts were concentrated in vacuo
  7. dissolutionThe residue was dissolved in 1:1 MeOH
  8. customDMSO (2 ml) and purified in 2 injections by MDAP (Method B)
  9. customwhich was repurified by MDAP (Method A)
  10. additionThe product containing fractions
  11. customwere evaporated under a stream of nitrogen

Sources & evidence

ORD record
ord-2512dc8f6de941faa20e64c7141fefdd
Source dataset
uspto-grants-2014_07
Patent number
US08765772B2

Reaction notes

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