Sodium Carbonate → 6-(2-Methoxyphenyl)pyrimidin-4-amine

HRID 1020019Notes

Reaction equation

HRID 1020019 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].[NH2:18][C:19]1[CH:24]=[C:23](Cl)[N:22]=[CH:21][N:20]=1>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:23]1[N:22]=[CH:21][N:20]=[C:19]([NH2:18])[CH:24]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2380124-Amino-6-chloropyrimidineHCID 27339582-Methoxyphenylboronic acid

Product 1

HCID 497584396-(2-Methoxyphenyl)pyrimidin-4-amineYield 58%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-methoxyphenylboronic acid (20.0 g, 155 mmol) in 500 ml of 1,4-dioxane was added 200 ml of saturated aqueous sodium carbonate solution. Argon gas was purged for 30 min at room temperature. 4-Amino-6-chloropyrimidine (28.1 g, 186 mmol) and tetrakistriphenylphosphinepalladium (9.00 g, 77.5 mmol) were added to reaction mixture simultaneously and argon gas was bubbled for another 40 min The reaction mixture was heated to reflux for 16 h, TLC confirms completion of reaction and the mixture was concentrated under reduced pressure. The residue was partitioned between DCM and water. The organic layer was separated, washed with brine, water, dried (Na2SO4) and concentrated. The obtained crude residue purified through silica gel column chromatography eluting with 15% ethyl acetate in DCM to provide 6-(2-methoxyphenyl)pyrimidin-4-amine (18.0 g, 58%). 1H-NMR: (DMSO-d6) δ=8.17 (1H, s), 7.71 (1H, d), 7.41 (1H, t), 6.96-7.06 (2H, m), 6.95 (1H, s), 3.98 (3H, s); MS (m/z)=202.1 (M+H).

Workup

  1. customArgon gas was purged for 30 min at room temperature
  2. customargon gas was bubbled for another 40 min The reaction mixture
  3. temperaturewas heated
  4. temperatureto reflux for 16 h
  5. customcompletion of reaction
  6. concentrationthe mixture was concentrated under reduced pressure
  7. customThe residue was partitioned between DCM and water
  8. customThe organic layer was separated
  9. washwashed with brine, water
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated
  12. customThe obtained crude residue
  13. custompurified through silica gel column chromatography
  14. washeluting with 15% ethyl acetate in DCM

Sources & evidence

ORD record
ord-0f22a46150be45e98053624e5e7df6c4
Source dataset
uspto-grants-2014_05
Patent number
US08716296B2

Reaction notes

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