Methylamine → 2-Chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine

HRID 1503472Notes

Reaction equation

HRID 1503472 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[CH2:13]([N:15](CC)CC)C.CN>CO>[Cl:1][C:2]1[N:7]=[C:6]([NH:15][CH3:13])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 6329MethylamineHCID 8471TriethylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidine

Product 1

HCID 210775872-Chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amineYield 45.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a cooled (−10° C.) solution of 2,4-dichloro-5-trifluoromethylpyrimidine (20 g, 0.089 mol) in methanol (100 mL) was added triethylamine (12.5 mL, 0.089 mol) and a 2 M solution of methylamine in methanol (45 mL). The reaction was allowed to warm to room temperature and stirred overnight. The reaction was then concentrated and re-dissolved in ethyl acetate. The solution was washed with sat. NaHCO3, brine, dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (5-25% EtOAc in heptane) to give 2-chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine (8.6 g, 45%). 1H-NMR (DMSO): δ 8.37 (s, 1H), 7.90 (s, 1H), 2.90 (s, 3H).

Workup

  1. concentrationThe reaction was then concentrated
  2. dissolutionre-dissolved in ethyl acetate
  3. washThe solution was washed with sat. NaHCO3, brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (5-25% EtOAc in heptane)

Sources & evidence

ORD record
ord-5319360eef6741a2b551cfc8dd76b9e2
Source dataset
uspto-grants-2015_12
Patent number
US09212186B2

Reaction notes

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