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

HRID 1022455Notes

Reaction equation

HRID 1022455 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([Cl:11])[C:5]2[CH:10]=[CH:9][NH:8][C:6]=2[N:7]=1.[H-].[Na+].Cl[CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20]>CN(C)C=O>[Cl:1][C:2]1[N:3]=[C:4]([Cl:11])[C:5]2[CH:10]=[CH:9][N:8]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 141168712,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 219764212,4-Dichloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidineYield 66.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (0.30 g, 1.6 mmol) in anhydrous N,N-dimethylformamide (5.5 mL) cooled to 0° C. was treated with a 60% dispersion of sodium hydride in mineral oil (82.5 mg, 2.06 mmol) under nitrogen. The reaction was stirred at 0° C. for 20-25 min. At this time, the reaction was then treated with (2-(chloromethoxy)ethyl)trimethylsilane (340 μL, 1.92 mmol) and was purged with nitrogen. The ice/water bath was removed, and the reaction was allowed to warm to room temperature where it stirred over 3 nights. At this time, the reaction was diluted with water (50 mL) and was extracted with ethyl acetate (2×50 mL). The combined organics were washed with water (50 mL) and a saturated aqueous sodium chloride solution (50 mL), dried over magnesium sulfate, filtered and rinsed with ethyl acetate, and concentrated in vacuo onto Celite®. Flash chromatography (12 g silica gel column, 1-30% ethyl acetate/hexanes) afforded 2,4-dichloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine as a viscous yellow oil (336.5 mg, 66.3%). 1H NMR (300 MHz, DMSO-d6) δ ppm −0.26-0.05 (m, 9H) 0.74-0.98 (m, 2H) 3.44-3.65 (m, 2H) 5.60 (s, 2H) 6.78 (d, J=3.77 Hz, 1H) 7.90 (d, J=3.77 Hz, 1H). LC-MS calcd. for C12H18Cl2N3OSi [(M+H)+] 318, obsd. 317.9.

Workup

  1. customwas purged with nitrogen
  2. customThe ice/water bath was removed
  3. temperatureto warm to room temperature where it
  4. stirringstirred over 3 nights
  5. additionAt this time, the reaction was diluted with water (50 mL)
  6. extractionwas extracted with ethyl acetate (2×50 mL)
  7. washThe combined organics were washed with water (50 mL)
  8. dry with materiala saturated aqueous sodium chloride solution (50 mL), dried over magnesium sulfate
  9. filtrationfiltered
  10. washrinsed with ethyl acetate
  11. concentrationconcentrated in vacuo onto Celite®

Sources & evidence

ORD record
ord-ad8806b544554747a3069e0772fd451f
Source dataset
uspto-grants-2014_05
Patent number
US08722661B2

Reaction notes

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