Sodium Carbonate → 2-Amino-4-chloro-6-(2-methyl-5-bromo-phenyl)-pyrimidine

HRID 28594Notes

Reaction equation

HRID 28594 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][C:3]=1B(O)O.[NH2:12][C:13]1[N:18]=[C:17](Cl)[CH:16]=[C:15]([Cl:20])[N:14]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:12][C:13]1[N:14]=[C:15]([Cl:20])[CH:16]=[C:17]([C:3]2[CH:4]=[C:5]([Br:8])[CH:6]=[CH:7][C:2]=2[CH3:1])[N:18]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 655222-Amino-4,6-dichloropyrimidineHCID 45097455(5-Bromo-2-methylphenyl)boronic acid

Product 1

HCID 860043412-Amino-4-chloro-6-(2-methyl-5-bromo-phenyl)-pyrimidineYield 80.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×

Procedure

To a mixture of 2-methyl-5-bromo-phenylboronic acid (7.0 g, 32.6 mmol), 2-amino-4,6-dichloropyrimidine (6.95 g, 42.4 mmol), and degassed ethylene glycol dimethyl ether (150 ml) was added a solution of sodium carbonate (17.3 g, 163 mmol) in water (50 ml). The mixture was stirred vigorously and palladium acetate (0.73 g, 3.26 mmol) was added followed by triphenylphosphine (1.71 g, 6.52 mmol). After stirring for 16 hours, the mixture was diluted with water (100 ml) and extracted with ethyl acetate (3×100 ml). The combined extracts were washed with water (100 ml), dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate-hexane (1:4) to provide 2-amino-4-chloro-6-(2-methyl-5-bromo-phenyl)-pyrimidine (7.8 g, 80% yield) as a pale yellow powder. 1H NMR (DMSO-d6) δ 7.58 (d, J=2.0 Hz, 1H), 7.55 (dd, J=2.0, 8.1 Hz, 1H), 7.28 (d, J=8.1 Hz, 1H), 7.26 (br s, 2H), 6.86 (s, 1H), 2.32 (s, 3H).

Workup

  1. customdegassed ethylene glycol dimethyl ether (150 ml)
  2. stirringAfter stirring for 16 hours
  3. extractionextracted with ethyl acetate (3×100 ml)
  4. washThe combined extracts were washed with water (100 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography on silica gel eluting with ethyl acetate-hexane (1:4)

Sources & evidence

ORD record
ord-88f4f451cb7243ae9ea021b4b88b2f50
Source dataset
uspto-grants-2008_09
Patent number
US07419984B2

Reaction notes

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