Ethyl Acetate → 2-Methylsulfanyl-6-(3-trifluoromethylphenyl)-pyrimidin-4-ylamine

HRID 2053090Notes

Reaction equation

HRID 2053090 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[C:4]([S:9][CH3:10])[N:3]=1.[F:11][C:12]([F:23])([F:22])[C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1.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>[CH3:10][S:9][C:4]1[N:3]=[C:2]([NH2:1])[CH:7]=[C:6]([C:17]2[CH:16]=[CH:15][CH:14]=[C:13]([C:12]([F:23])([F:22])[F:11])[CH:18]=2)[N:5]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 704964-Amino-6-chloro-2-methylthiopyrimidineHCID 27343883-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 585132282-Methylsulfanyl-6-(3-trifluoromethylphenyl)-pyrimidin-4-ylamineYield 60.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

To a stirred solution of 4-amino-6-chloro-2-methylthiopyrimidine (3.5 g) in toluene (45 mL) under a nitrogen atmosphere was added, sequentially, (3-trifluoromethylphenyl)boronic acid (4.15 g), potassium carbonate (25 mL, 2M) and tetrakis(triphenylphosphine)palladium(0) (1.16 g). The mixture was heated to reflux for ten hours and stirred at room temperature over the weekend. Ethyl acetate (150 mL) was added and the mixture washed with water (2×100 mL). Organics were separated, washed with saturated sodium chloride (100 mL), dried over sodium sulphate and solvent was evaporated under reduced pressure to yield crude product. Purification by flash chromatography yielded product 2-methylsulfanyl-6-(3-trifluoromethyl-phenyl)-pyrimidin-4-ylamine (3.45 g)

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for ten hours
  3. washthe mixture washed with water (2×100 mL)
  4. customOrganics were separated
  5. washwashed with saturated sodium chloride (100 mL)
  6. dry with materialdried over sodium sulphate and solvent
  7. customwas evaporated under reduced pressure
  8. customto yield crude product
  9. customPurification by flash chromatography

Sources & evidence

ORD record
ord-0826825d8ea24d95b250cc29bdfd2742
Source dataset
uspto-grants-2008_02
Patent number
US07326715B2

Reaction notes

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