Dimethylformamide → HCID 90040927, compound

HRID 523017Notes

Reaction equation

HRID 523017 reaction equation
FC(F)(F)[C:3](OC(=O)C(F)(F)F)=[O:4].CN(C)C=O.[Br:19][C:20]1[N:21]=[C:22]2[CH:29]=[CH:28][N:27]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:23]2=[N:24][C:25]=1[CH3:26]>ClCCl>[Br:19][C:20]1[N:21]=[C:22]2[C:29]([CH:3]=[O:4])=[CH:28][N:27]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:36])([CH3:35])[CH3:37])[C:23]2=[N:24][C:25]=1[CH3:26]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 9845Trifluoroacetic anhydrideHCID 90041354HCID 90041354, compound

Product 1

HCID 90040927HCID 90040927, compoundYield 84.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic anhydride (10.2 mL, 60.8 mmol) was added dropwise, with cooling (ice bath), to N,N-dimethylformamide (24 mL) under an argon atmosphere. The cooling bath was removed for 15 min to facilitate stirring and then replaced. A solution of 2-bromo-3-methyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine (3.47 g, 10.1 mmol) in dichloromethane (5 mL) was added dropwise. The cooling bath was removed; the mixture was stirred for 15 min, then set in a bath at 45° C. and stirred for 16 h. The mixture was cooled, then poured onto ice water (200 mL) containing sodium carbonate (13 g) and extracted four 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 on (silica, 20% ethyl acetate in hexanes) gave 2-bromo-3-methyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (3.17 g, 84%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm −0.09 (s, 9H), 0.85 (t, J=8.0 Hz, 2H), 2.71 (s, 3H), 3.58 (t, J=8.0 Hz, 2H), 5.68 (s, 2H), 8.87 (s, 1H), 10.04 (s, 1H).

Workup

  1. temperaturewith cooling (ice bath)
  2. customThe cooling bath was removed for 15 min
  3. customThe cooling bath was removed
  4. stirringthe mixture was stirred for 15 min
  5. customset in a bath at 45° C.
  6. stirringstirred for 16 h
  7. temperatureThe mixture was cooled
  8. additionpoured onto ice water (200 mL)
  9. additioncontaining sodium carbonate (13 g)
  10. extractionextracted four times with ether
  11. washThe combined ether extracts were washed twice with water
  12. dry with materialdried over anhydrous magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customPurification by chromatography on (silica, 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-710b1f46e38b4d008606a0db466dbe3b
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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