Sodium hydride → HCID 66630814, compound

HRID 2382483Notes

Reaction equation

HRID 2382483 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@H:11]2[C@@H:15]3[O:16][C:17]([CH3:20])([CH3:19])[O:18][C@@H:14]3[C@@H:13]([NH:21][C:22](=[O:25])[CH2:23][CH3:24])[CH2:12]2)=[C:4]([NH:26][CH2:27][CH:28]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:3]=1.[H-].[Na+].[Cl:43][C:44]1[CH:49]=[CH:48][C:47]([CH2:50][CH2:51][OH:52])=[CH:46][CH:45]=1>C1COCC1>[Cl:43][C:44]1[CH:49]=[CH:48][C:47]([CH2:50][CH2:51][O:52][C:2]2[N:10]=[C:9]3[C:5]([N:6]=[CH:7][N:8]3[C@H:11]3[C@@H:15]4[O:16][C:17]([CH3:20])([CH3:19])[O:18][C@@H:14]4[C@@H:13]([NH:21][C:22](=[O:25])[CH2:23][CH3:24])[CH2:12]3)=[C:4]([NH:26][CH2:27][CH:28]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[N:3]=2)=[CH:46][CH:45]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74647p-Chlorophenethylic alcoholHCID 86647566HCID 86647566, compound

Product 1

HCID 66630814HCID 66630814, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

The title compound is prepared by adding N-{(3aR,4S,6R,6aS)-6-[2-Chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,2-dimethyl-tetrahydro-cyclopenta[1,3]dioxol-4-yl}-propionamide (example 235, step 1) to a premixed solution of sodium hydride (60% in oil) and 2-(4-chloro-phenyl)-ethanol (1 equivalent) in dry THF. The reaction is stirred at 50° C. for 48 hours, before quenching residual sodium hydride with excess aqueous ammonium chloride. The reaction mixture id then partitioned between ethyl acetate and water; the organic phase is washed consecutively with water and brine before drying over magnesium sulfate. Filtration and removal of the volatile components under reduced pressure yields the crude product; purification by column chromatography/crystallisation affords the title compound.

Workup

  1. custombefore quenching residual sodium hydride with excess aqueous ammonium chloride
  2. customThe reaction mixture id then partitioned between ethyl acetate and water
  3. washthe organic phase is washed consecutively with water and brine
  4. dry with materialbefore drying over magnesium sulfate
  5. filtrationFiltration and removal of the volatile components under reduced pressure
  6. customyields the crude product

Sources & evidence

ORD record
ord-959e549406b04c8694c19bafea170953
Source dataset
uspto-grants-2012_09
Patent number
US08258141B2

Reaction notes

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