Potassium Phosphate, Tribasic → N-{3-[(Ethylsulfanyl)methyl]phenyl}-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-amine

HRID 2277750Notes

Reaction equation

HRID 2277750 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:9]=2[O:15][CH3:16])[C:5]([F:17])=[CH:4][N:3]=1.[CH2:18]([S:20][CH2:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][CH:28]=1)[NH2:25])[CH3:19].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.CN1C(=O)CCC1.C(OCC)(=O)C>[CH2:18]([S:20][CH2:21][C:22]1[CH:23]=[C:24]([NH:25][C:2]2[N:7]=[C:6]([C:8]3[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:9]=3[O:15][CH3:16])[C:5]([F:17])=[CH:4][N:3]=2)[CH:26]=[CH:27][CH:28]=1)[CH3:19]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 284129373-[(Ethylsulfanyl)methyl]anilineHCID 867296092-Chloro-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidine

Product 1

HCID 89444793N-{3-[(Ethylsulfanyl)methyl]phenyl}-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-amine

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2-chloro-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidine (750 mg; 2.92 mmol), 3-[(ethylsulfanyl)methyl]aniline (376 mg; 2.24 mmol), chloro(2-dicyclohexylphosphino-2′,4′,6′-tri-iso-propyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) methyl-tert-butylether adduct (139 mg; 0.17 mmol; ABCR GmbH & CO. KG) and 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl (80 mg; 0.17 mmol; Aldrich Chemical Company Inc.) and potassium phosphate (2.39 g; 11.24 mmol) in toluene (15 ml) and NMP (3 mL) was stirred at 130° C. for 3 hours. After cooling, the batch was diluted with ethyl acetate and washed with aqueous sodium chloride solution. The organic phase was filtered using a Whatman filter and concentrated. The residue was purified by chromatography (hexane/ethyl acetate 2:1) to give the pure product (536 mg; 1.38 mmol).

Workup

  1. temperatureAfter cooling
  2. washwashed with aqueous sodium chloride solution
  3. filtrationThe organic phase was filtered
  4. filtrationfilter
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography (hexane/ethyl acetate 2:1)
  7. customto give the pure product (536 mg; 1.38 mmol)

Sources & evidence

ORD record
ord-0fb91c6055cc4ddcbcbce59d772fd9fe
Source dataset
uspto-grants-2015_09
Patent number
US09133171B2

Reaction notes

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