Diisopropylethylamine → (+/-)-[1-(2,4-Dichloro-pyrimidin-5-yl)-ethyl]-(2-fluoro-4-methoxy-phenyl)-amine

HRID 2216971Notes

Reaction equation

HRID 2216971 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([CH:9](Br)[CH3:10])=[CH:4][N:3]=1.C(N(CC)C(C)C)(C)C.[F:21][C:22]1[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[CH:25][C:23]=1[NH2:24]>C(#N)C>[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([CH:9]([NH:24][C:23]2[CH:25]=[CH:26][C:27]([O:29][CH3:30])=[CH:28][C:22]=2[F:21])[CH3:10])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 37563832-Fluoro-4-methoxyanilineHCID 21908975(+/-)-2,4-Dichloro-5-(1-bromoethyl)-pyrimidine

Product 1

HCID 10358358(+/-)-[1-(2,4-Dichloro-pyrimidin-5-yl)-ethyl]-(2-fluoro-4-methoxy-phenyl)-amine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of (±)-2,4-dichloro-5-(1-bromoethyl)-pyrimidine (0.20 g; 0.79 mmol) (from Example 1c supra), N,N-diisopropylethyl-amine (140 μL; 0.80 mmol) (Aldrich) and 2-fluoro-4-methoxyaniline (0.11 g; 0.78 mmol) (from Example 8a supra) were combined in acetonitrile (3 mL) and stirred at room temperature overnight. The reaction was found to be incomplete and was then heated in an oil bath at 40–50° C. overnight. Upon cooling, the reaction was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. Purification by flash chromatography (Biotage, 40S; 10:90 to 20:80 ethyl acetate-hexanes gradient) gave (±)-[1-(2,4-dichloro-pyrimidin-5-yl)-ethyl]-(2-fluoro-4-methoxy-phenyl)-amine. (Yield 0.12 g; 49.1%).

Workup

  1. temperaturewas then heated in an oil bath at 40–50° C. overnight
  2. temperatureUpon cooling
  3. customthe reaction was partitioned between ethyl acetate and water
  4. washThe organic phase was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash chromatography (Biotage, 40S; 10:90 to 20:80 ethyl acetate-hexanes gradient)

Sources & evidence

ORD record
ord-fe35d0f949864b499c3889292d5b1ece
Source dataset
uspto-grants-2006_09
Patent number
US07112676B2

Reaction notes

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