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

HRID 1294432Notes

Reaction equation

HRID 1294432 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([Cl:9])=[C:4]([Cl:10])[N:3]=1.[CH3:11][C:12]1[CH:18]=[C:17]([CH3:19])[CH:16]=[C:15]([CH3:20])[C:13]=1[NH2:14].CC(N(C(C)C)CC)C>O1CCOCC1>[Cl:10][C:4]1[C:5]([Cl:9])=[C:6]([Cl:8])[N:7]=[C:2]([NH:14][C:13]2[C:15]([CH3:20])=[CH:16][C:17]([CH3:19])=[CH:18][C:12]=2[CH3:11])[N:3]=1.[Cl:1][C:2]1[N:3]=[C:4]([NH:14][C:13]2[C:15]([CH3:20])=[CH:16][C:17]([CH3:19])=[CH:18][C:12]=2[CH3:11])[C:5]([Cl:9])=[C:6]([Cl:8])[N:7]=1

Participants

6

Reactant 3

HCID 69132,4,6-TrimethylanilineHCID 156902,4,5,6-TetrachloropyrimidineHCID 81531Diisopropylethylamine

Product 2

HCID 221700912,5,6-trichloro-N-(2,4,6-trimethylphenyl)4-pyrimidinamineHCID 221700944,5,6-trichloro-N-(2,4,6-trimethylphenyl)-2-pyrimidinamine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
55 °C

Procedure

2,4,5,6-tetrachloropyrimidine (0.0134 mol), 1,4-dioxane (30 ml), 2,4,6-trimethyl aniline (0.0134 mol), and N,N-bis(1-methylethyl)ethanamine (0.0136 mol) were added to a flask under argon and stirred at 55° C. for 16 hours. The solvent was evaporated, and the residue was dissolved in CH2Cl2, then purified by column chromatography over silica gel (eluent: CH2Cl2/hexane 1/4, and 1/2). The desired fractions were collected and their solvent was evaporated, yielding 0.15 g 4,5,6-trichloro-N-(2,4,6-trimethylphenyl)-2-pyrimidinamine (interm. 6) and 3.15 g 2,5,6-trichloro-N-(2,4,6-trimethylphenyl)-4-pyrimidinamine (interm. 7). b) A mixture of intermediate 7 (0.00474 mol) in NH3, (2.0 M in 2-propanol; 20 ml) was heated in a pressure vessel at 75–80° C. for 40 hours. The temperature was increased to 110–115° C. The solvent was evaporated to produce 1.85 g of residue. The sample was heated with NH3, (0.5 M in 1,4-dioxane; 20 ml) at 125° C. for 18 hours. The solvent was evaporated, yielding 1.7 g of a mixture of two isomers, i.e. 2,5-dichloro-N4-(2,4,6-trimethylphenyl)-4,6-pyrimidinediamine (interm. 8) and 5,6-dichloro-N4-(2,4,6-trimethylphenyl)-2,4-pyrimidinediamine (interm. 9).

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue was dissolved in CH2Cl2
  3. custompurified by column chromatography over silica gel (eluent: CH2Cl2/hexane 1/4, and 1/2)
  4. customThe desired fractions were collected
  5. customtheir solvent was evaporated

Sources & evidence

ORD record
ord-94e3fe82c0514bfbbaaf2ab01f5046c4
Source dataset
uspto-grants-2007_07
Patent number
US07241458B1

Reaction notes

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