Water → 5-(3-Pyridinyl)-2-pyrazinamine

HRID 1875900Notes

Reaction equation

HRID 1875900 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.Br[C:11]1[N:12]=[CH:13][C:14]([NH2:17])=[N:15][CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+].O>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(OCC)(=O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:11]2[N:12]=[CH:13][C:14]([NH2:17])=[N:15][CH:16]=2)[CH:2]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 5995392-Amino-5-bromopyrazineHCID 27343783-Pyridinylboronic acid

Product 1

HCID 457877085-(3-Pyridinyl)-2-pyrazinamineYield 60.9%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Pyridin-3-ylboronic acid (307 mg, 2.50 mmol), 5-bromopyrazin-2-amine (391 mg, 2.25 mmol) and dichlorobis(triphenylphosphine)-palladium(II) (88 mg, 0.13 mmol) were added to degassed dioxane (12 mL) and the mixture was stirred for 30 min. Then sodium carbonate (795 mg, 7.50 mmol) and degassed water (8 mL) were added and the reaction was heated in a closed reaction vial at 100° C. for 8 h. The reaction was allowed to stand at ambient temperature over the weekend. It was diluted into ethyl acetate (100 mL) and extracted with brine (3×25 mL). The organic layers were dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (0 to 5% methanol/ethyl acetate) to afford 5-(pyridin-3-yl)pyrazin-2-amine (235 mg, 1.37 mmol, 54.6% yield). 1H NMR (400 MHz, Acetone) δ ppm 9.13 (1H, d, J=1.51 Hz), 8.54 (1H, d, J=1.26 Hz), 8.50 (1H, dd, J=4.78, 1.51 Hz), 8.22-8.28 (1H, m), 8.07 (1H, d, J=1.26 Hz), 7.39 (1H, ddd, J=7.87, 4.72, 0.76 Hz), 6.05 (2H, br. s.). MS (LC/MS) R.T.=0.58; [M+H]+=173.20.

Workup

  1. customto degassed dioxane (12 mL)
  2. additionwere added
  3. customto stand at ambient temperature over the weekend
  4. extractionextracted with brine (3×25 mL)
  5. dry with materialThe organic layers were dried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography (0 to 5% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-93a808b56e6643b986edbb76d3a355e6
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

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