2,4,6-Trimethylaniline → 5-bromo-2-chloro-N-(2,4,6-trimethylphenyl)-4-pyrimidinamine

HRID 1814902

Reaction equation

HRID 1814902 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[NH2:10].[Br:11][C:12]1[C:13]([Cl:19])=[N:14][C:15]([Cl:18])=[N:16][CH:17]=1.CC(N(C(C)C)CC)C>O1CCOCC1>[Br:11][C:12]1[C:13]([Cl:19])=[N:14][C:15]([NH:10][C:3]2[C:4]([CH3:9])=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=2[CH3:1])=[N:16][CH:17]=1.[Br:11][C:12]1[C:13]([NH:10][C:3]2[C:4]([CH3:9])=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=2[CH3:1])=[N:14][C:15]([Cl:18])=[N:16][CH:17]=1

Participants

6

Reactant 3

HCID 69132,4,6-TrimethylanilineHCID 81531DiisopropylethylamineHCID 2899735-Bromo-2,4-dichloropyrimidine

Product 2

HCID 221700865-bromo-2-chloro-N-(2,4,6-trimethylphenyl)-4-pyrimidinamineYield 65%HCID 221701025-bromo4-chloro-N-(2,4,6-trimethylphenyl)-2-pyrimidinamineYield 24%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

Reaction under argon atmosphere. A solution of 2,4,6-trimethylbenzenamine (0.00461 mol) in 1,4-dioxane (5 ml) was added to a solution of 5-bromo-2,4-dichloropyrimidine (0.00439 mol) in 1,4-dioxane (5 ml). N,N-bis(1-methylethyl)ethanamine (0.00548 mol) was added. The reaction mixture was stirred and refluxed for 20 hours. The solvent was evaporated. The residue was dissolved in ethyl acetate, washed with a saturated aqueous sodium bicarbonate solution, water and brine, dried with sodium sulfate, filtered, and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: 1:5, 1:2 and 1:1 CH2Cl2: hexane). Two pure fraction groups were collected and their solvent was evaporated, yielding 0.35 g (24%) of 5-bromo-4-chloro-N-(2,4,6-trimethylphenyl)-2-pyrimidinamine (interm. 1) and 0.93 g (65%) of 5-bromo-2-chloro-N-(2,4,6-trimethylphenyl)-4-pyrimidinamine (interm. 2).

Workup

  1. customReaction under argon atmosphere
  2. temperaturerefluxed for 20 hours
  3. customThe solvent was evaporated
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with a saturated aqueous sodium bicarbonate solution, water and brine
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue was purified by column chromatography over silica gel (eluent: 1:5, 1:2 and 1:1 CH2Cl2: hexane)
  10. customTwo pure fraction groups were collected
  11. customtheir solvent was evaporated

Sources & evidence

ORD record
ord-b186d8c8816945a3972f27eb5457bcd1
Source dataset
uspto-grants-2005_04
Patent number
US06878717B2

Linked notes

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