Dimethylformamide → HCID 178425937, compound

HRID 1747683Notes

Reaction equation

HRID 1747683 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([SH:8])[CH:5]=[CH:6][CH:7]=1.CN(C=O)C.[H-].[Na+].[Si:16]([O:23][C@@H:24]1[C@H:28]([CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH2:27][C@@H:26]([O:38][C:39]2[N:47]=[CH:46][N:45]=[C:44]3[C:40]=2[N:41]=[C:42](I)[N:43]3C2CCCCO2)[CH2:25]1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]>>[Si:16]([O:23][C@@H:24]1[C@H:28]([CH2:29][O:30][Si:31]([C:34]([CH3:35])([CH3:36])[CH3:37])([CH3:32])[CH3:33])[CH2:27][C@@H:26]([O:38][C:39]2[N:47]=[CH:46][N:45]=[C:44]3[C:40]=2[N:41]=[C:42]([S:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[CH:3]=2)[NH:43]3)[CH2:25]1)([C:19]([CH3:20])([CH3:21])[CH3:22])([CH3:17])[CH3:18]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 79303-ThiocresolHCID 24758Sodium hydrideHCID 667979406-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]-oxy}methyl)cyclopentyl]oxy}-8-iodo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Product 1

HCID 178425937HCID 178425937, compoundYield 82.1%

Procedure

To a solution of 3-methylbenzenethiol (0.55 mL, 0.0046 mol) in DMF (10 mL, 0.2 mol) was added sodium hydride (0.093 g, 0.0023 mol). The mixture was stirred at room temperature for 10 minutes and then 6-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentyl]oxy}-8-iodo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (400 mg, 0.0006 mol) (Example 115, steps a-b) was added and the solution was heated at 150° C. for 8 hours. The reaction was cooled, quenched by addition of water and the mixture was extracted with ethyl acetate, washed with water, brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (0 to 30% ethyl acetate/hexanes) to obtain 296 mg (80%) of the title compound.

Workup

  1. temperaturethe solution was heated at 150° C. for 8 hours
  2. temperatureThe reaction was cooled
  3. customquenched by addition of water
  4. extractionthe mixture was extracted with ethyl acetate
  5. washwashed with water, brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography (0 to 30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-8303ac52ba91487db9f6b86b6e4ad855
Source dataset
uspto-grants-2015_10
Patent number
US09150525B2

Reaction notes

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