Methanol → HCID 58010044, compound

HRID 1969712Notes

Reaction equation

HRID 1969712 reaction equation
Br[C:2]1[N:3]=[C:4]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:5]2=[N:6][CH:7]=1.[CH3:21][OH:22].CN([CH:26]=[O:27])C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[S:11]([N:8]1[C:5]2=[N:6][CH:7]=[C:2]([C:21]([O:27][CH3:26])=[O:22])[N:3]=[C:4]2[CH:10]=[CH:9]1)([C:14]1[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=1)(=[O:13])=[O:12]

Participants

5

Reactant 3

HCID 887MethanolHCID 6228DimethylformamideHCID 529876432-Bromo-5-((4-methylphenyl)sulfonyl)-5H-pyrrolo(2,3-b)pyrazine

Product 1

HCID 58010044HCID 58010044, compound

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
95 °C

Procedure

CO was bubbled into an orange solution of 2-bromo-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (50.0 g, 142 mmol) in DMF (2.50 L) within a 5 L round bottom flask for about 2 min. Bis(triphenylphosphine)-palladium(II) dichloride (9.96 g, 14.2 mmol), TEA (59 mL, 423 mmol) and MeOH (173.0 mL, 4259 mmol) were added and the flask was fitted with a balloon of CO. The mixture was heated at about 95° C. under an atmosphere of CO (1 atmosphere). After stirring overnight, the reaction mixture was cooled to ambient temperature overnight and poured into ice water (3.2 L). The mixture was stirred for about 10 min and the precipitate was collected by filtration, while washing with water, and dried for 1 h. The crude material was dissolved in DCM, separated from residual water, dried over anhydrous MgSO4, filtered, added silica gel, and concd under reduced pressure to prepare for chromatography. The crude material was purified by silica gel column chromatography eluting with 0-5% MeOH in DCM to yield methyl 5-tosyl-5H-pyrrolo[2,3-b]pyrazine-2-carboxylate with 5 mol % DCM as an excipient (40.7 g, 86%, 93% purity): LC/MS (Table 1, Method a) Rt=2.35 min; MS m/z 332 (M+H)+.

Workup

  1. customthe flask was fitted with a balloon of CO
  2. temperaturethe reaction mixture was cooled to ambient temperature overnight
  3. stirringThe mixture was stirred for about 10 min
  4. filtrationthe precipitate was collected by filtration
  5. washwhile washing with water
  6. customdried for 1 h
  7. dissolutionThe crude material was dissolved in DCM
  8. customseparated from residual water
  9. dry with materialdried over anhydrous MgSO4
  10. filtrationfiltered
  11. additionadded silica gel, and concd under reduced pressure
  12. customto prepare for chromatography
  13. customThe crude material was purified by silica gel column chromatography
  14. washeluting with 0-5% MeOH in DCM

Sources & evidence

ORD record
ord-95ce9e014ef649b88a96d24ac549e4a3
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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