Water → 2-(Cyclopentyloxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

HRID 527816Notes

Reaction equation

HRID 527816 reaction equation
[CH:1]1([OH:6])[CH2:5][CH2:4][CH2:3][CH2:2]1.CC(C)([O-])C.[Na+].F[C:14]1[N:22]=[C:21]2[C:17]([N:18]=[CH:19][N:20]2[CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)=[C:16]([NH2:29])[N:15]=1.O>COCCOC.C(OCC)(=O)C>[CH:1]1([O:6][C:14]2[N:22]=[C:21]3[C:17]([N:18]=[CH:19][N:20]3[CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][O:24]3)=[C:16]([NH2:29])[N:15]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 962WaterHCID 7298CyclopentanolHCID 23676156Sodium t-butoxideHCID 592525662-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Product 1

HCID 592526292-(Cyclopentyloxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amineYield 78.5%

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Cyclopentanol (25 ml, 275 mmol) was added to sodium tert-butoxide (4.05 g, 42.2 mmol) to give a thick suspension which was diluted with 1,2-dimethoxyethane (35 ml) and heated to 50° C. 2-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (2.5 g, 10.54 mmol) was added to the resulting solution which was then stirred under nitrogen at 50° C. for 20 hours. The mixture was cooled and water and ethyl acetate were added. The layers separated and the aqueous layer washed again with ethyl acetate. The organic extracts were combined, washed with brine, dried over anhydrous magnesium sulphate and concentrated under reduced pressure at 40° C. The residue was loaded in cyclohexane (50 ml) onto 330 g silica cartridge and eluted firstly with a 0-100% ethyl acetate in cyclohexane gradient over 10 column volumes and then with a 0-30% methanol in ethyl acetate gradient. Product-containing fractions were combined and evaporated to give the title compound as a white foam (2.51 g).

Workup

  1. customto give a thick suspension which
  2. temperatureThe mixture was cooled
  3. customThe layers separated
  4. washthe aqueous layer washed again with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried over anhydrous magnesium sulphate
  7. concentrationconcentrated under reduced pressure at 40° C
  8. washeluted firstly with a 0-100% ethyl acetate in cyclohexane gradient over 10 column volumes
  9. customevaporated

Sources & evidence

ORD record
ord-9eecae5d59584d76be929c9a63ed6e01
Source dataset
uspto-grants-2016_05
Patent number
US09346806B2

Reaction notes

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