Hydrochloric Acid → N4-Phenyl-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine

HRID 1977680Notes

Reaction equation

HRID 1977680 reaction equation
[C:1]1([NH:7][C:8]2[CH:13]=[CH:12][N:11]=[C:10](Cl)[N:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH:21]=[C:22]([O:26][CH3:27])[C:23]=1[O:24][CH3:25])[NH2:20].Cl>CC(C)=O.O>[C:1]1([NH:7][C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:20][C:19]3[CH:21]=[C:22]([O:26][CH3:27])[C:23]([O:24][CH3:25])=[C:17]([O:16][CH3:15])[CH:18]=3)[N:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 322853,4,5-TrimethoxyanilineHCID 219953492-Chloro-N-phenylpyrimidin-4-amine

Product 1

HCID 21995345N4-Phenyl-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamineYield 76.8%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent2×HCID 962WaterSolvent

Procedure

A solution of N-phenyl-2-chloro-4-pyrimidineamine (1.83 g, 8.91 mmol) and 3,4,5-trimethoxyaniline (1.83 g, 10.0 mmol) in acetone (10 ml) and water (15 ml) containing concentrated hydrochloric acid (0.2 ml) was heated at reflux for 10 h. On cooling the acetone was removed under reduced pressure, and the reaction taken to pH10 with 4N NaOH and extracted with ethyl acetate (2×75 ml). The combined organic layers were dried (MgSO4), concentrated under reduced pressure and the residue crystallised from ethyl acetate to give the title compound (2.41 g) as a colourless solid m.p. 191°. δH (CDCl3) 8.04 (1H, d, J 5.8 Hz), 7.37-7.34 (4H, m), 7.16-7.10 (1H, m), 7.05 (1H, br s), 6.85 (2H, s), 6.68 (1H, br s), 6.16 (1H, d, J 5.8 Hz), 3.82 (3H, s) and 3.81 (6H, s). MS m/z 353 (M+H)+. The pyrimidineamine used as starting material was prepared by heating a solution of 2,4-dichloropyrimidine (4.0 g, 26.8 mmol), aniline (2.46 ml, 27.0 mmol) and triethylamine (4.3ml, 30.0 mmol) in ethanol (50 ml) at reflux for 2 h. On cooling a white precipitate was collectd which was washed with cold ethanol (100 ml) and recrystallised from ethyl acetate to give the desired product (6.01 g) as a colourless solid m.p. 186°. MS/mz 206 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 10 h
  3. customwas removed under reduced pressure
  4. extractionextracted with ethyl acetate (2×75 ml)
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customthe residue crystallised from ethyl acetate

Sources & evidence

ORD record
ord-06b45b8ab030445a9a06eeda4b73f9fe
Source dataset
uspto-grants-2001_05
Patent number
US06235746B1

Reaction notes

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