Sodium Carbonate → HCID 58009875, compound

HRID 1854390Notes

Reaction equation

HRID 1854390 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.[CH:21](/B(O)O)=[CH:22]\[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.O.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:21](/[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)=[CH:22]\[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

8

Reactant 3

HCID 10340Sodium Carbonate2×HCID 5702628Styrylboronic acid2×HCID 529876432-Bromo-5-((4-methylphenyl)sulfonyl)-5H-pyrrolo(2,3-b)pyrazine

Product 1

HCID 58009875HCID 58009875, compoundYield 36.3%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-bromo-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (3.1 g, 8.8 mmol, Preparation #7), PdCl2(dppf).DCM (0.719 g, 0.880 mmol) and (E)-styrylboronic acid (2.60 g, 17.6 mmol) in THF (3 mL) and water (2 mL) was added Na2CO3 (2.33 g, 22.0 mmol). The reaction mixture was degassed with argon for about 5 min. The reaction mixture was heated to about 50° C. After about 24 h, additional PdCl2(dppf).DCM (0.719 g, 0.880 mmol), (E)-styrylboronic acid (2.60 g, 17.6 mmol) and Na2CO3 (2.33 g, 22.0 mmol) were added to the reaction mixture. After heating at about 50° C. for about 48 h, the reaction mixture was cooled to ambient temperature and diluted with DCM (200 mL) and water (200 mL). The organic layer was separated, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. Purification by chromatography over silica gel eluting with a gradient of 20-60% EtOAc in heptane containing 5% DCM provided (E)-2-styryl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine as a yellow solid (1.2 g, 36%). LC/MS (Table 2, Method a) Rt=2.99 min; MS m/z: 376 (M+H)+.

Workup

  1. customThe reaction mixture was degassed with argon for about 5 min
  2. temperatureAfter heating at about 50° C. for about 48 h
  3. temperaturethe reaction mixture was cooled to ambient temperature
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by chromatography over silica gel eluting with a gradient of 20-60% EtOAc in heptane containing 5% DCM

Sources & evidence

ORD record
ord-64f511ab856c47ad91bd5a5a9a5377aa
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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