Acetic Acid → N-(4-iodophenyl)pyrimidin-2-amine

HRID 1752050Notes

Reaction equation

HRID 1752050 reaction equation
Cl[C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C(O)(=O)C.[I:12][C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=1.C(=O)([O-])O.[Na+]>O1CCOCC1>[I:12][C:13]1[CH:19]=[CH:18][C:16]([NH:17][C:2]2[N:7]=[CH:6][CH:5]=[CH:4][N:3]=2)=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 108934-IodoanilineHCID 744042-ChloropyrimidineHCID 516892Sodium Bicarbonate

Product 1

HCID 57762548N-(4-iodophenyl)pyrimidin-2-amineYield 54.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Under an argon atmosphere, 2-chloropyrimidine (16.5 g) and acetic acid (11.7 ml) were added to a solution of 4-iodoaniline (30 g) in dioxane (500 ml), and the resulting mixture was stirred for 13 hours while heating the mixture to reflux. The reaction solution was cooled to room temperature and saturated aqueous sodium hydrogen carbonate solution was added thereto, followed by extracting the resulting mixture 4 times with ethyl acetate. Organic layers were washed 3 times with saturated brine and dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the filtrate was concentrated. The residue was purified by column chromatography (silica gel, eluent: cyclohexane/ethyl acetate=4/1). The product was recrystallized from dichloromethane/hexane mixed solvent to obtain N-(4-iodophenyl)pyrimidin-2-amine (22.27 g). NMR (H1, CDCl3): δ 6.73 (1H, t, J=4.6 Hz), 7.18 (1H, brs), 7.40-7.42 (2H, m), 7.59-7.61 (2H, m), 8.41 (2H, d, J=4.6 Hz)

Workup

  1. temperaturewhile heating the mixture
  2. temperatureto reflux
  3. extractionby extracting the resulting mixture 4 times with ethyl acetate
  4. washOrganic layers were washed 3 times with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customAfter removing anhydrous sodium sulfate
  7. filtrationby filtration
  8. concentrationthe filtrate was concentrated
  9. customThe residue was purified by column chromatography (silica gel, eluent: cyclohexane/ethyl acetate=4/1)
  10. customThe product was recrystallized from dichloromethane/hexane mixed solvent

Sources & evidence

ORD record
ord-32dee9ac6e26493d9a99145a7e0c6ec0
Source dataset
uspto-grants-2015_10
Patent number
US09162988B2

Reaction notes

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