Sodium hydride → 2-Chloro-4-cyclobutoxy-5-iodo-7-((2-(trimethylsilyl)ethoxy)-methyl)-7H-pyrrolo[2,3-d]pyrimidine

HRID 1487624Notes

Reaction equation

HRID 1487624 reaction equation
[H-].[Na+].[CH:3]1([OH:7])[CH2:6][CH2:5][CH2:4]1.[Cl:8][C:9]1[N:10]=[C:11](Cl)[C:12]2[C:17]([I:18])=[CH:16][N:15]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:13]=2[N:14]=1>C1COCC1>[Cl:8][C:9]1[N:10]=[C:11]([O:7][CH:3]2[CH2:6][CH2:5][CH2:4]2)[C:12]2[C:17]([I:18])=[CH:16][N:15]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:13]=2[N:14]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 76218CyclobutanolHCID 866796212,4-dichloro-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo(2,3-d)pyrimidine

Product 1

HCID 867264532-Chloro-4-cyclobutoxy-5-iodo-7-((2-(trimethylsilyl)ethoxy)-methyl)-7H-pyrrolo[2,3-d]pyrimidineYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
30 °C

Procedure

To a suspension of sodium hydride (2 equiv, 60% in mineral oil) in dry THF (0.44 M) under nitrogen atmosphere was added a solution of cyclobutanol (1.05 equiv) in dry THF (1.4 M) at 0° C. The reaction mixture was stirred at room temperature for 30 minutes before 2,4-dichloro-5-iodo-7-((2-(trimethylsilyl)ethoxy)-methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv) in dry THF (0.33 M) was added and the resulting reaction mixture was stirred at 30° C. for 1 h. The reaction mixture was quenched with saturated aqueous ammonium chloride solution. The organic solvent was removed under reduced pressure and the resulting aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated under reduced pressure. The crude obtained was purified by flash column chromatography on silica gel (5% ethyl acetate in petroleum ether) to afford the title compound (95% yield) as a white solid. MS (ESI) m/z 479.2 [M+1]+.

Workup

  1. additionwas added
  2. customthe resulting reaction mixture
  3. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution
  4. customThe organic solvent was removed under reduced pressure
  5. extractionthe resulting aqueous layer was extracted with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customThe filtrate was evaporated under reduced pressure
  10. customThe crude obtained
  11. customwas purified by flash column chromatography on silica gel (5% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-e354a7682f6f469da66c844bb99aaff1
Source dataset
uspto-grants-2016_08
Patent number
US09428509B2

Reaction notes

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