Ethanol → 2-Amino-4-anilino-6-methylaminopyrimidine

HRID 931697Notes

Reaction equation

HRID 931697 reaction equation
[NH2:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([NH:9][CH3:10])[N:3]=1.NC1[N:17]=[C:16](Cl)[CH:15]=[C:14](Cl)N=1.[CH3:20]N.[CH2:22](O)[CH3:23]>>[NH2:1][C:2]1[N:7]=[C:6]([NH:17][C:16]2[CH:15]=[CH:14][CH:23]=[CH:22][CH:20]=2)[CH:5]=[C:4]([NH:9][CH3:10])[N:3]=1

Participants

5

Reactant 4

HCID 702EthanolHCID 6329MethylamineHCID 655222-Amino-4,6-dichloropyrimidine2×HCID 2354466-Chloro-n4-methylpyrimidine-2,4-diamine

Product 1

HCID 807680532-Amino-4-anilino-6-methylaminopyrimidine

Conditions

Temperature
70 °C

Procedure

2-Amino-4-anilino-6-methylaminopyrimidine was synthesized, via 2-amino-4-chloro-6-methylaminopyrimidine, with 2-amino-4,6-dichloropyrimidine as a starting material. 2-Amino-4,6-dichloropyrimidine (32.8 g), a 40% aqueous methylamine solution (34.5 mL), and ethanol (300 mL) were mixed, followed by stirring at an internal temperature of 70° C. for 4 hours. Subsequently, the solvent was concentrated under reduced pressure, and crystallization from acetonitrile was performed. The product was collected by filtration and was used without purification for the subsequent step. The crude product of 2-amino-4-chloro-6-methylaminopyrimidine, aniline (27.4 mL), methoxyethanol (100 mL), and hydrochloric acid (0.2 mL) were mixed, followed by stirring with heating at 120° C. for 3 hours. After cooling, the reaction solution was added to sodium bicarbonate water (500 mL)/ethyl acetate under ice cooling to extract the product with ethyl acetate. After concentration, purification by column chromatography (ethyl acetate/methanol) was performed to yield 18 g of 2-amino-4-anilino-6-methylaminopyrimidine. Synthesis was performed as in Synthetic example 1a-1 with 2-amino-4-anilino-6-methylaminopyrimidine, methyl m-methylbenzoate, and sodium methoxide. The product was purified by silica gel column chromatography using ethyl acetate/n-hexane and recrystallization from ethyl acetate/n-hexane to yield compound (6-14).

Workup

  1. concentrationSubsequently, the solvent was concentrated under reduced pressure, and crystallization from acetonitrile
  2. filtrationThe product was collected by filtration
  3. customwas used without purification for the subsequent step
  4. additionThe crude product of 2-amino-4-chloro-6-methylaminopyrimidine, aniline (27.4 mL), methoxyethanol (100 mL), and hydrochloric acid (0.2 mL) were mixed
  5. stirringby stirring
  6. temperaturewith heating at 120° C. for 3 hours
  7. temperatureAfter cooling
  8. additionthe reaction solution was added to sodium bicarbonate water (500 mL)/ethyl acetate under ice cooling
  9. extractionto extract the product with ethyl acetate
  10. concentrationAfter concentration, purification by column chromatography (ethyl acetate/methanol)

Sources & evidence

ORD record
ord-0d0d9d0435ef49dc965ba775ff927d5f
Source dataset
uspto-grants-2016_03
Patent number
US09296877B2

Reaction notes

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