3-benzylamino-4-(3-chloro-phenylamino)-1H-pyrazolo[3,4-d]pyrimidine → HCID 178509242, compound

HRID 1068876Notes

Reaction equation

HRID 1068876 reaction equation
C([NH:8][C:9]1[C:17]2[C:12](=[N:13][CH:14]=[N:15][C:16]=2[NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=2)[NH:11][N:10]=1)C1C=CC=CC=1>C1C=CC=CC=1>[NH2:8][C:9]1[C:17]2[C:12](=[N:13][CH:14]=[N:15][C:16]=2[NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=2)[NH:11][N:10]=1

Participants

3

Reactant 1

HCID 53278353-benzylamino-4-(3-chloro-phenylamino)-1H-pyrazolo[3,4-d]pyrimidine

Product 1

HCID 178509242HCID 178509242, compound

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Conditions

Temperature
80 °C

Procedure

Starting with a suspension of 75.8 g (216 mmol) of 3-benzylamino-4-(3-chlorophenylamino)-1H-pyrazolo[3,4-d]pyrimidine in 1.5 liters of benzene, some of the solvent is distilled off for the purpose of removing residual water. Then, with the exclusion of moisture, the suspension is added to 84 g of aluminium chloride (Fluka, Buchs/Switzerland) in 500 ml of benzene and heated at 80° C. for 2.5 hours. The reaction mixture is cooled to RT, the supernatant benzene phase is poured into 2 kg of ice-water (leaving behind a green oily residue), and the solid that separates out is filtered off with suction and washed thoroughly with water (→K1). Using a rotary evaporator, the benzene is evaporated off from the filtrate and the aqueous phase that remains behind is added to the green oily residue together with 1 kg of ice and hydrolyzed at 40° C. for 2 hours. The crystalline product is filtered off with suction and washed with water (K2). K1 and K2 are taken up in 1 liter of methanol, acidified with 4N aqueous HCl and partially concentrated by evaporation. Water is added and the methanol is evaporated off completely. The crystals are filtered off and washed with water. The same purification procedure is repeated using semi-saturated Na2CO3 solution/methanol and water/methanol. Stirring at 50° C. in methanol, precipitation with diethyl ether, filtration and drying yield 3-amino-4-(3-chloro-phenylamino)-1H-pyrazolo[3,4-d]pyrimidine; m.p. 232-234° C.; TLC: Rf=0.50 (ethyl acetate).

Workup

  1. distillationsome of the solvent is distilled off for the purpose
  2. customof removing residual water
  3. additionThen, with the exclusion of moisture, the suspension is added to 84 g of aluminium chloride (Fluka, Buchs/Switzerland) in 500 ml of benzene
  4. temperatureThe reaction mixture is cooled to RT
  5. additionthe supernatant benzene phase is poured into 2 kg of ice-water (
  6. customleaving behind a green oily residue), and the solid that separates
  7. filtrationout is filtered off with suction
  8. washwashed thoroughly with water (→K1)
  9. customa rotary evaporator
  10. customthe benzene is evaporated off from the filtrate
  11. additionbehind is added to the green oily residue together with 1 kg of ice and hydrolyzed at 40° C. for 2 hours
  12. filtrationThe crystalline product is filtered off with suction
  13. washwashed with water (K2)
  14. concentrationpartially concentrated by evaporation
  15. additionWater is added
  16. customthe methanol is evaporated off completely
  17. filtrationThe crystals are filtered off
  18. washwashed with water
  19. customThe same purification procedure
  20. customprecipitation
  21. filtrationwith diethyl ether, filtration
  22. customdrying

Sources & evidence

ORD record
ord-02956fcb1c214dfe9cd8529ce5bf1830
Source dataset
uspto-grants-2001_06
Patent number
US06251911B1

Reaction notes

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