Sodium hydride → 6-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]-oxy}methyl)cyclopentyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

HRID 447686Notes

Reaction equation

HRID 447686 reaction equation
[H-].[Na+].[Si:3]([O:10][C@@H:11]1[C@H:15]([CH2:16][O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[CH2:14][C@@H:13]([OH:25])[CH2:12]1)([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].Cl[C:27]1[N:35]=[CH:34][N:33]=[C:32]2[C:28]=1[N:29]=[CH:30][N:31]2[CH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][O:37]1>CN(C=O)C>[Si:3]([O:10][C@@H:11]1[C@H:15]([CH2:16][O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:19])[CH3:20])[CH2:14][C@@H:13]([O:25][C:27]2[N:35]=[CH:34][N:33]=[C:32]3[C:28]=2[N:29]=[CH:30][N:31]3[CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][O:37]2)[CH2:12]1)([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 59671236(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentanol

Product 1

HCID 596712146-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]-oxy}methyl)cyclopentyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

In DMF (4 mL, 0.05 mol) was suspended sodium hydride (47 mg, 0.0012 mol) at 0° C., to which was added a solution of (1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentanol (0.200 g, 0.000554 mol) in 2.5 mL DMF. The mixture was stirred at 0° C. for 10 minutes and was added a solution of 6-Chloro-9-(tetrahydropyranyl)purine (0.265 g, 0.00111 mol) (Example 33, step b) in 4 mL DMF. The reaction was stirred at 0° C. for 1 h and warmed to 23° C. overnight. The reaction was quenched by addition of saturated aqueous NH4Cl, and the mixture was extracted with ethyl acetate, washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (0 to 5% acetone/toluene) to obtain 271 mg (86.8%).

Workup

  1. customat 0° C.
  2. stirringThe reaction was stirred at 0° C. for 1 h
  3. temperaturewarmed to 23° C. overnight
  4. customThe reaction was quenched by addition of saturated aqueous NH4Cl
  5. extractionthe mixture was extracted with ethyl acetate
  6. washwashed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography (0 to 5% acetone/toluene)
  11. customto obtain 271 mg (86.8%)

Sources & evidence

ORD record
ord-b3f8801d6f1b4e7ea5a11467d926042b
Source dataset
uspto-grants-2013_07
Patent number
US08481550B2

Reaction notes

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