N,N-Dimethylaniline → HCID 86732869, compound

HRID 1579322Notes

Reaction equation

HRID 1579322 reaction equation
CN(C)C1C=CC=CC=1.[CH3:10][O:11][C:12]([C:14]1[CH:19]=[C:18]([O:20][CH3:21])[C:17]([CH2:22][C:23]2[C:24]([NH2:31])=[N:25][C:26]([NH2:30])=[N:27][C:28]=2O)=[C:16]([O:32][CH3:33])[CH:15]=1)=[O:13].P(Cl)(Cl)([Cl:36])=O>>[CH3:10][O:11][C:12]([C:14]1[CH:19]=[C:18]([O:20][CH3:21])[C:17]([CH2:22][C:23]2[C:24]([NH2:31])=[N:25][C:26]([NH2:30])=[N:27][C:28]=2[Cl:36])=[C:16]([O:32][CH3:33])[CH:15]=1)=[O:13]

Participants

4

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 178498553HCID 178498553, compound

Product 1

HCID 86732869HCID 86732869, compound

Procedure

2.4 G. of N,N-dimethyl-aniline were added dropwise with stirring to a suspension of 3.4 g. of α-(2,4-diamino-6-hydroxy-5-pyrimidinyl)-2,6-dimethoxy-p-toluic acid methyl ester in 25.6 g. of phosphorus oxychloride. The resulting mixture was brought to the boiling temperature in the course of 1 hour and then boiled at reflux for 4 hours. Thereafter, two thirds of the phosphorus oxychloride were removed by distillation under reduced pressure. The residue was poured onto 80 g. of ice with stirring and left to stand for two days at room temperature. The suspension was treated with 38 ml. of 25% aqueous ammonia, while the temperature did not exceed 20°C. After 2 hours, the solid material was removed by filtration with suction, rinsed with a small amount of water in a flask and separated from the N,N-dimethyl-aniline with steam. After cooling, the compound in suspension was removed by filtration with suction and taken up in ethyl acetate. The solution was dried over magnesium sulfate and the solvent evaporated. The dark residue (1.6 g.) was purified by column chromatography on 60 g. of silica gel (Merck) using chloroform/n-propanol/25% ammonia (80:20:1) as the eluant, whereby there was obtained α-(2,4-diamino-6-chloro-5-pyrimidinyl)-2,6-dimethoxy-p-toluic acid methyl ester having a m.p. of 228°-229°C. (from methanol).

Workup

  1. customwas brought to the boiling temperature in the course of 1 hour
  2. temperatureat reflux for 4 hours
  3. customThereafter, two thirds of the phosphorus oxychloride were removed by distillation under reduced pressure
  4. additionThe residue was poured onto 80 g
  5. stirringof ice with stirring
  6. waitleft
  7. additionThe suspension was treated with 38 ml
  8. customdid not exceed 20°C
  9. waitAfter 2 hours
  10. customthe solid material was removed by filtration with suction
  11. washrinsed with a small amount of water in a flask
  12. customseparated from the N,N-dimethyl-aniline with steam
  13. temperatureAfter cooling
  14. customthe compound in suspension was removed by filtration with suction
  15. dry with materialThe solution was dried over magnesium sulfate
  16. customthe solvent evaporated
  17. customThe dark residue (1.6 g.) was purified by column chromatography on 60 g

Sources & evidence

ORD record
ord-85116bbca8744ab0800129ea09f0c6a7
Source dataset
uspto-grants-1976_01
Patent number
US03931181

Reaction notes

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