(4-Chloro-phenyl)-(6-chloro-pyrazin-2-yl)-carbamic acid tert-butyl ester → (4-Chloro-phenyl)-[6-(6-methyl-pyridin-2-yl)-pyrazin-2-yl]-carbamic acid tert-butyl ester

HRID 1961704Notes

Reaction equation

HRID 1961704 reaction equation
[Br-].[CH3:2][C:3]1[N:8]=[C:7]([Zn+])[CH:6]=[CH:5][CH:4]=1.[C:10]([O:14][C:15](=[O:31])[N:16]([C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=1)[C:17]1[CH:22]=[N:21][CH:20]=[C:19](Cl)[N:18]=1)([CH3:13])([CH3:12])[CH3:11]>O1CCCC1.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>[C:10]([O:14][C:15](=[O:31])[N:16]([C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=1)[C:17]1[CH:22]=[N:21][CH:20]=[C:19]([C:7]2[CH:6]=[CH:5][CH:4]=[C:3]([CH3:2])[N:8]=2)[N:18]=1)([CH3:13])([CH3:12])[CH3:11]

Participants

5

Reactant 2

HCID 59570677(4-Chloro-phenyl)-(6-chloro-pyrazin-2-yl)-carbamic acid tert-butyl esterHCID 178426002HCID 178426002, compound

Product 1

HCID 59570656(4-Chloro-phenyl)-[6-(6-methyl-pyridin-2-yl)-pyrazin-2-yl]-carbamic acid tert-butyl esterYield 37.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Bis(triphenylphosphine)palladium(II) dichloride (54 mg, 0.076 mmol) was dissolved in degassed tetrahydrofuran (5 mL) Diisobutylaluminum hydride (1M in hexanes, 0.15 mL, 0.15 mmol) was added and the mixture was stirred for 15 minutes. 6-Methyl-2-pyridylzinc bromide (0.5 M in tetrahydrofuran, 2.29 mL, 1.15 mmol) and a solution of (4-chloro-phenyl)-(6-chloro-pyrazin-2-yl)-carbamic acid tert-butyl ester (260 mg, 0.76 mmol) in tetrahydrofuran (3 mL) was added and the mixture was stirred at room temperature over night. The reaction was quenched with aqueous sodium hydrogen carbonate. The aqueous phase was extracted with ethyl acetate (4×15 mL). The combined organic phases were washed with brine, dried over anhydrous sodium sulphate, filtrated and evaporated. The crude product was purified by column chromatography (ethyl acetate/heptane as eluent) to give (4-chloro-phenyl)-[6-(6-methyl-pyridin-2-yl)-pyrazin-2-yl]-carbamic acid tert-butyl ester (113 mg, 23%) as a yellow solid.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at room temperature over night
  3. customThe reaction was quenched with aqueous sodium hydrogen carbonate
  4. extractionThe aqueous phase was extracted with ethyl acetate (4×15 mL)
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over anhydrous sodium sulphate
  7. filtrationfiltrated
  8. customevaporated
  9. customThe crude product was purified by column chromatography (ethyl acetate/heptane as eluent)

Sources & evidence

ORD record
ord-ced20d67e8394d0db55f3978fc8ef0f3
Source dataset
uspto-grants-2013_04
Patent number
US08415358B2

Reaction notes

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