Sodium hydride → 2-Chloro-5-iodo-4-(1-methylcyclobutoxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine

HRID 1487652Notes

Reaction equation

HRID 1487652 reaction equation
[H-].[Na+].[CH3:3][C:4]1([OH:8])[CH2:7][CH2:6][CH2:5]1.[Cl:9][C:10]1[N:11]=[C:12](Cl)[C:13]2[C:18]([I:19])=[CH:17][N:16]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:14]=2[N:15]=1>C1COCC1>[Cl:9][C:10]1[N:11]=[C:12]([O:8][C:4]2([CH3:3])[CH2:7][CH2:6][CH2:5]2)[C:13]2[C:18]([I:19])=[CH:17][N:16]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:14]=2[N:15]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1406421-MethylcyclobutanolHCID 866796212,4-dichloro-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo(2,3-d)pyrimidine

Product 1

HCID 867264842-Chloro-5-iodo-4-(1-methylcyclobutoxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidineYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
60 °C

Procedure

To a suspension of sodium hydride (60% in mineral oil, 2.0 equiv) in dry THF (0.45 M) under a nitrogen atmosphere was added a solution of 1-methylcyclobutanol (1.2 equiv) in dry THF (0.27 M) at 0° C. The reaction mixture was stirred at 30° C. for 30 min before a solution of 2,4-dichloro-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv) in dry THF (0.23 M) was added and the resulting reaction mixture was heated at 60° C. for 2 h. After the reaction was completed, the reaction mixture was quenched with saturated aqueous ammonium chloride solution. The organic solvent was removed under vacuum and the 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 product was purified by silica gel chromatography (2% ethyl acetate in petroleum ether) to afford the title compound (77% yield) as a yellow oil. MS (ESI) m/z 494.2 [M+H]+.

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 vacuum
  5. extractionthe 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 product was purified by silica gel chromatography (2% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-a6659e6c9d014de0bb0229167a04045f
Source dataset
uspto-grants-2016_08
Patent number
US09428509B2

Reaction notes

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