Acetonitrile → 2-Bromo-7-(2-methoxy-phenyl)-5-(toluene-4-sulfonyl)-5H-pyrrolo[2,3-b]pyrazine

HRID 272049Notes

Reaction equation

HRID 272049 reaction equation
[Br:1][C:2]1[N:3]=[C:4]2[C:10](I)=[CH:9][N:8]([S:12]([C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1.[CH3:22][O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O.C(#N)C.C(=O)(O)[O-].[Na+]>Cl[Pd-2](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.C(OCC)(=O)C>[Br:1][C:2]1[N:3]=[C:4]2[C:10]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[O:23][CH3:22])=[CH:9][N:8]([S:12]([C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 516892Sodium Bicarbonate2×HCID 27339582-Methoxyphenylboronic acidHCID 457896312-Bromo-7-iodo-5-tosyl-5H-pyrrolo[2,3-B]pyrazine

Product 1

HCID 598360452-Bromo-7-(2-methoxy-phenyl)-5-(toluene-4-sulfonyl)-5H-pyrrolo[2,3-b]pyrazineYield 34%

Reagents, catalysts & solvents 2

HCID 178418903HCID 178418903, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A 50-ml round bottom flask was charged with 2-Bromo-7-iodo-5-(toluene-4-sulfonyl)-5H-pyrrolo[2,3-b]pyrazine (423 mg, 0.885 mmol), 2-methoxyphenylboronic acid (148 mg (0.973 mmol) and dichlorobis(triphenylphosphino)palladium(II) (31 mg, 0.04 mmol). To this mixture was added acetonitrile (10 mL) and a 2 M aqueous solution of sodium bicarbonate (5 mL). The reaction mixture was stirred at 40° C. for 1 hour, then 55° C. for another hour. The crude reaction mixture was distributed between ethyl acetate and a saturated aqueous solution of sodium bicarbonate. The aqueous phase was then extracted with ethyl acetate and the combined organic phases were dried over sodium sulfate, filtered and concentrated. The crude product was then purified by flash silica gel chromatography using a gradient of ethyl acetate in hexanes to afford 2-Bromo-7-(2-methoxy-phenyl)-5-(toluene-4-sulfonyl)-5H-pyrrolo[2,3-b]pyrazine (139 mg, 34% yield) as a light yellow solid; the bis-addition product 2,7-Bis-(2-methoxy-phenyl)-5-(toluene-4-sulfonyl)-5H-pyrrolo[2,3-b]pyrazine (213 mg, 50% yield) was also obtained. MS: m/z 457.9/460.0 [MH+]; MS: m/z 486.1 [MH+] (bis-addition product).

Workup

  1. wait55° C. for another hour
  2. customThe crude reaction mixture
  3. extractionThe aqueous phase was then extracted with ethyl acetate
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was then purified by flash silica gel chromatography

Sources & evidence

ORD record
ord-718f76d8927c41199bc9b9b327d279f0
Source dataset
uspto-grants-2008_11
Patent number
US07452993B2

Reaction notes

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