Sodium hydride → 2,6-Dichloro-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-purine

HRID 577686

Reaction equation

HRID 577686 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([Cl:11])[N:3]=1.[H-].[Na+].[CH3:14][Si:15]([CH2:18][CH2:19][O:20][CH2:21]Cl)([CH3:17])[CH3:16]>CN(C=O)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:21][O:20][CH2:19][CH2:18][Si:15]([CH3:17])([CH3:16])[CH3:14])=[C:4]([Cl:11])[N:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 53244122,6-Dichloropurine

Product 1

HCID 582852322,6-Dichloro-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-purineYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2,6-dichloropurine (4.0 g, 21 mmol) in DMF (100 mL) was cooled to 0° C. NaH (1.69 g, 42.3 mmol, 60% dispersion in mineral oil) was added, and the mixture was stirred at rt for 30 min. The reaction was again cooled to 0° C., and SEM-Cl (5.29 g, 31.7 mmol) was added. The reaction was stirred at rt for 1 hr, at which point LCMS showed complete consumption of starting material. Water was added slowly, and the mixture was extracted with EtOAc (three times). The combined organics were washed with water (three times) and brine, dried over Mg2SO4, and filtered. The filtrate was concentrated, and the crude material was purified by flash chromatography on a Biotage 40M column; eluted with 0%-20% EtOAc/heptane to afford the title compound (3.82 g, 57% yield) as a pale yellow oil. 1H NMR (400 MHz, chloroform-d) δ ppm 8.26 (s, 1H) 5.64 (s, 2H) 3.61-3.67 (m, 2H) 0.92-1.00 (m, 2H) −0.01 (s, 9H).

Workup

  1. temperatureThe reaction was again cooled to 0° C.
  2. stirringThe reaction was stirred at rt for 1 hr, at which point LCMS
  3. customconsumption of starting material
  4. additionWater was added slowly
  5. extractionthe mixture was extracted with EtOAc (three times)
  6. washThe combined organics were washed with water (three times) and brine
  7. dry with materialdried over Mg2SO4
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated
  10. customthe crude material was purified by flash chromatography on a Biotage 40M column
  11. washeluted with 0%-20% EtOAc/heptane

Sources & evidence

ORD record
ord-ae577014c043496ba879626f9c69a81f
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Linked notes

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