Sodium hydride → HCID 86679607, compound

HRID 577660Notes

Reaction equation

HRID 577660 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([Cl:12])[C:5]2[C:10]([F:11])=[CH:9][NH:8][C:6]=2[N:7]=1.[H-].[Na+].Cl[CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21]>CN(C=O)C>[Cl:1][C:2]1[N:3]=[C:4]([Cl:12])[C:5]2[C:10]([F:11])=[CH:9][N:8]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 594420712,4-Dichloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 86679607HCID 86679607, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

2,4-Dichloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine (see Seela, et al., Helvetica Chimica Acta, 91(6):1083-1105 (2008)) (654 mg, 3.2 mmol) was dissolved in DMF (6.5 mL). After cooling to 0° C., NaH (254 mg, 6.35 mmol, 60% in mineral oil) was added. After complete addition, the mixture was warmed to rt and allowed to stir for 30 min. A solution of (2-(chloromethoxy)ethyl)trimethylsilane (529 mg, 3.2 mmol) in DMF (2 mL) was added dropwise to the mixture and stirring was continued for 3 hrs. The reaction was quenched by pouring the mixture over ice water (75 mL). The resulting aqueous layer was then extracted with Et2O (three×50 mL). The combined organics were washed with water (two times), brine (two times) and dried over MgSO4. After concentrating, the brown solid was purified via flash chromatography eluting with a gradient of 1%-10% EtOAc in heptanes to afford the title compound (0.45 g, 42% yield) as a white, low melting solid. 1H NMR (400 MHz, chloroform-d) δ ppm-0.03 (s, 9H), 0.87-0.97 (m, 2H), 3.48-3.58 (m, 2H), 5.57 (s, 2H), 7.14 (d, J=2.78 Hz, 1H). APCI (MH+). m/z (APCI+) for C12H16Cl2FN3OSi 336.2 (M+H)+.

Workup

  1. additionAfter complete addition
  2. temperaturethe mixture was warmed to rt
  3. stirringstirring
  4. waitwas continued for 3 hrs
  5. customThe reaction was quenched
  6. additionby pouring the mixture over ice water (75 mL)
  7. extractionThe resulting aqueous layer was then extracted with Et2O (three×50 mL)
  8. washThe combined organics were washed with water (two times), brine (two times)
  9. dry with materialdried over MgSO4
  10. concentrationAfter concentrating
  11. customthe brown solid was purified via flash chromatography
  12. washeluting with a gradient of 1%-10% EtOAc in heptanes

Sources & evidence

ORD record
ord-2b94fc42d06e4beca7dc36344dae1df0
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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