Sodium hydride → 4-Chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo(2,3-d)pyrimidine

HRID 1617337Notes

Reaction equation

HRID 1617337 reaction equation
[H-].[Na+].[Cl:3][C:4]1[N:9]=[CH:8][NH:7][C:6]2=[N:10][CH:11]=[CH:12][C:5]=12.[CH3:13][Si:14]([CH3:21])([CH3:20])[CH2:15][CH2:16][O:17][CH2:18]Cl>CN(C)C(=O)C>[Cl:3][C:4]1[C:5]2[CH:12]=[CH:11][N:10]([CH2:18][O:17][CH2:16][CH2:15][Si:14]([CH3:21])([CH3:20])[CH3:13])[C:6]=2[N:7]=[CH:8][N:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178418725HCID 178418725, compound

Product 1

HCID 467367974-Chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo(2,3-d)pyrimidine

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of sodium hydride (36.141 g, 903.62 mmol) in N,N-dimethylacetamide (118 mL) at −5° C. (ice/salt bath) was added a dark solution of 4-chloropyrrolo[2,3-d]pyrimidine (119.37 g, 777.30 mmol) in N,N-dimethylacetamide (237 mL) slowly. The flask and addition funnel were rinsed with N,N-dimethylacetamide (30 mL). A large amount of gas was evolved immediately. The mixture became a slightly cloudy orange mixture. The mixture was stirred at 0° C. for 60 min to give a light brown turbid mixture. To the mixture was slowly added [2-(trimethylsilyl)ethoxy]methyl chloride (152.40 g, 914.11 mmol) and the reaction was stirred at 0° C. for 1 h. The reaction was quenched by addition of 12 mL of H2O slowly. More water (120 mL) was added followed by methyl tert-butyl ether (MTBE) (120 mL). The mixture was stirred for 10 min. The organic layer was separated. The aqueous layer was extracted with another portion of MTBE (120 mL). The organic extracts were combined, washed with brine (120 mL×2) and concentrated under reduced pressure to give the crude product 4-chloro-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine as a dark oil. Yield: 85.07 g (97%); LC-MS: 284.1 (M+H)+. It was carried to the next reaction without purification.

Workup

  1. additionThe flask and addition funnel
  2. washwere rinsed with N,N-dimethylacetamide (30 mL)
  3. customto give a light brown turbid mixture
  4. stirringthe reaction was stirred at 0° C. for 1 h
  5. customThe reaction was quenched by addition of 12 mL of H2O slowly
  6. additionMore water (120 mL) was added
  7. stirringThe mixture was stirred for 10 min
  8. customThe organic layer was separated
  9. extractionThe aqueous layer was extracted with another portion of MTBE (120 mL)
  10. washwashed with brine (120 mL×2)
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b6b37429af9544efabb0dda592d77398
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

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