Diisopropylethylamine → 6-Chloro-2-pyrazin-2-yl-N-[(1S)-2,2,2-trifluoro-1-methylethyl]-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine

HRID 2112601Notes

Reaction equation

HRID 2112601 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[C:13]([F:14])=[CH:12][C:11]([F:15])=[CH:10][C:9]=2[F:16])=[C:6](Cl)[N:5]=[C:4]([C:18]2[CH:23]=[N:22][CH:21]=[CH:20][N:19]=2)[N:3]=1.Cl.[F:25][C:26]([F:31])([F:30])[C@@H:27]([NH2:29])[CH3:28].C(N(CC)C(C)C)(C)C>CN(C)C=O>[Cl:1][C:2]1[N:3]=[C:4]([C:18]2[CH:23]=[N:22][CH:21]=[CH:20][N:19]=2)[N:5]=[C:6]([NH:29][C@@H:27]([CH3:28])[C:26]([F:31])([F:30])[F:25])[C:7]=1[C:8]1[C:9]([F:16])=[CH:10][C:11]([F:15])=[CH:12][C:13]=1[F:14]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 130939192-Propanamine, 1,1,1-trifluoro-, hydrochloride (1:1), (2S)-HCID 589101014,6-Dichloro-2-(pyrazin-2-yl)-5-(2,4,6-trifluorophenyl)pyrimidine

Product 1

HCID 112819276-Chloro-2-pyrazin-2-yl-N-[(1S)-2,2,2-trifluoro-1-methylethyl]-5-(2,4,6-trifluorophenyl)pyrimidin-4-amineYield 44.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4,6-dichloro-2-pyrazin-2-yl-5-(2,4,6-trifluorophenyl)pyrimidine (205 mg, 0.57 mmol), (1S)-2,2,2-trifluoro-1-methylethylamine hydrogen chloride (298 mg, 2 mmol), and N,N-diisopropylethylamine (258 mg, 2 mmol) in 5 mL of N,N-dimethylformamide is stirred at 90° C. in a sealed tube for 18 h. The reaction mixture is partitioned between ethyl acetate and saturated sodium chloride. The organic layer is washed with saturated sodium chloride (×3), dried over magnesium sulfate, and concentrated. The residue is chromatographed over silica gel, eluting with a gradient of 20% ethyl acetate in hexanes to 50% ethyl acetate in hexanes. Concentration provides 6-chloro-2-pyrazin-2-yl-N-[(1S)-2,2,2-trifluoro-1-methylethyl]-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine as a light yellow solid (111 mg). MS: m/z 434.1 (M+H).

Workup

  1. customThe reaction mixture is partitioned between ethyl acetate and saturated sodium chloride
  2. washThe organic layer is washed with saturated sodium chloride (×3)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue is chromatographed over silica gel
  6. washeluting with a gradient of 20% ethyl acetate in hexanes to 50% ethyl acetate in hexanes
  7. concentrationConcentration

Sources & evidence

ORD record
ord-d78fd58339684d8f978a620fbf971c92
Source dataset
uspto-grants-2009_04
Patent number
US07524849B2

Reaction notes

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