Sodium hydride → HCID 90041354, compound

HRID 523016Notes

Reaction equation

HRID 523016 reaction equation
[Br:1][C:2]1[N:3]=[C:4]2[CH:11]=[CH:10][NH:9][C:5]2=[N:6][C:7]=1[CH3:8].[H-].[Na+].Cl[CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20]>CN(C)C=O>[Br:1][C:2]1[N:3]=[C:4]2[CH:11]=[CH:10][N:9]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:5]2=[N:6][C:7]=1[CH3:8]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 707008922-Bromo-3-methyl-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 90041354HCID 90041354, compoundYield 56.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of the crude 2-bromo-3-methyl-5H-pyrrolo[2,3-b]pyrazine (3.83 g, 18 mmol) prepared above and N, N-dimethylformamide (25 mL), under an atmosphere of argon and cooled in an ice bath, was added 95% sodium hydride oil dispersion (0.912 g, 36 mmol) (gas evolution). The mixture was stirred for 15 minutes, and then (2-chloromethoxy-ethyl)-trimethylsilane (3.61 g, 22 mmol) in N, N-dimethylformamide (3 mL) was added dropwise. After 10 minutes, the cooling bath was removed and the mixture stirred for another 3½ hours at room temperature. The mixture was cooled in an ice bath, quenched by the addition of water, and then poured into water and extracted three times with ether. The combined ether extracts were washed twice with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Purification by chromatography (silica, 15% ethyl acetate in hexanes) gave 2-bromo-3-methyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine (3.47 g, 56%) as an amber solid. 1H NMR (400 MHz, DMSO-d6) δ ppm −0.11 (s, 9H), 0.82 (m, 2H), 2.67 (s, 3H), 3.51 (m, 2H), 5.59 (s, 2H), 6.67 (d, J=3.5 Hz, 1H), 8.01 (d, J=3.5 Hz, 1H).

Workup

  1. temperatureunder an atmosphere of argon and cooled in an ice bath
  2. waitAfter 10 minutes
  3. customthe cooling bath was removed
  4. stirringthe mixture stirred for another 3½ hours at room temperature
  5. temperatureThe mixture was cooled in an ice bath
  6. customquenched by the addition of water
  7. additionpoured into water
  8. extractionextracted three times with ether
  9. washThe combined ether extracts were washed twice with water
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customPurification by chromatography (silica, 15% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-91432e925e1b46aa81773245d0262878
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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