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

HRID 1487594Notes

Reaction equation

HRID 1487594 reaction equation
[CH:1]1([OH:6])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[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:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]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 7298CyclopentanolHCID 24758Sodium hydrideHCID 866796212,4-dichloro-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo(2,3-d)pyrimidine

Product 1

HCID 867264232-Chloro-4-(cyclopentyloxy)-5-iodo-7-[[2-(trimethylsilyl)ethoxy]methyl]-7H-pyrrolo[2,3-d]pyrimidineYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of cyclopentanol (1 equiv) in anhydrous THF (0.22 M) was added sodium hydride (60% in mineral oil, 1.3 equiv) at 0° C. under nitrogen. After the resulting reaction mixture was stirred at room temperature for 30 min, 2,4-dichloro-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (0.67 equiv) was added. The reaction was stirred at room temperature for 4 h and quenched with saturated aqueous ammonium chloride solution. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and filtered. Concentration under vacuum gave the crude product, which was purified by silica gel column chromatography (5% ethyl acetate in petroleum ether) to afford the title compound (46% yield). MS (ESI) m/z 493.2. [M+1]+.

Workup

  1. customAfter the resulting reaction mixture
  2. stirringThe reaction was stirred at room temperature for 4 h
  3. customquenched with saturated aqueous ammonium chloride solution
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationConcentration under vacuum
  9. customgave the crude product, which
  10. customwas purified by silica gel column chromatography (5% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-33161f72a5b243f8a9f80da6b669b1f5
Source dataset
uspto-grants-2016_08
Patent number
US09428509B2

Reaction notes

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