Azetidine → 9-[4-(1-Azetidinyl)butyl]-2-(butyloxy)-8-(methyloxy)-9H-purin-6-amine

HRID 590434Notes

Reaction equation

HRID 590434 reaction equation
[CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:20][CH3:21])[N:12]2[CH2:15][CH2:16][CH2:17][CH2:18]Cl)=[C:8]([NH2:22])[N:7]=1)[CH2:2][CH2:3][CH3:4].[NH:23]1[CH2:26][CH2:25][CH2:24]1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[N:23]1([CH2:18][CH2:17][CH2:16][CH2:15][N:12]2[C:11]([O:20][CH3:21])=[N:10][C:9]3[C:13]2=[N:14][C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])=[N:7][C:8]=3[NH2:22])[CH2:26][CH2:25][CH2:24]1

Participants

5

Reactant 3

HCID 10422Azetidine2×HCID 81531Diisopropylethylamine2×HCID 592526152-(Butyloxy)-9-(4-chlorobutyl)-8-(methyloxy)-9H-purin-6-amine

Product 1

HCID 592526359-[4-(1-Azetidinyl)butyl]-2-(butyloxy)-8-(methyloxy)-9H-purin-6-amineYield 7.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

2-(Butyloxy)-9-(4-chlorobutyl)-8-(methyloxy)-9H-purin-6-amine (100 mg, 0.305 mmol), azetidine (0.021 ml, 0.305 mmol) and N,N-diisopropylethylamine (0.107 ml, 0.610 mmol) were dissolved in DMF (2 ml) and heated at 50° C. for 48 hours. LCMS indicated the reaction to be incomplete and additional azetidine (0.021 ml, 0.305 mmol) and N,N-diisopropylethylamine (0.107 ml, 0.610 mmol) were added and the reaction mixture heated at 50° C. for a further 48 hours. The mixture was then partitioned between DCM (4 ml) and water (4 ml) and the layers separated using a hydrophobic frit. The aqueous phase was re-extracted with DCM (4 ml) and the combined organic extracts were concentrated and the residue purified by MDAP (Method A). The product-containing fractions were evaporated under a stream of nitrogen to give the title compound as a clear gum (7.6 mg).

Workup

  1. customthe reaction
  2. temperaturethe reaction mixture heated at 50° C. for a further 48 hours
  3. customThe mixture was then partitioned between DCM (4 ml) and water (4 ml)
  4. customthe layers separated
  5. extractionThe aqueous phase was re-extracted with DCM (4 ml)
  6. concentrationthe combined organic extracts were concentrated
  7. customthe residue purified by MDAP (Method A)
  8. customThe product-containing fractions were evaporated under a stream of nitrogen

Sources & evidence

ORD record
ord-6d85eadc441f4683bb4abb5c9dee2013
Source dataset
uspto-grants-2016_01
Patent number
US09233962B2

Reaction notes

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