Formamide → Arprinocid

HRID 905327Notes

Reaction equation

HRID 905327 reaction equation
[NH2:1][C:2]1[C:7](C2C=CC=CC=2)=[C:6]([NH:14][CH2:15][C:16]2[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:23])[N:5]=[C:4](N=NC2N=CC=CN=2)[N:3]=1.S(S([O-])=O)([O-])=O.[Na+].[Na+].[CH:40]([NH2:42])=O>>[NH2:1][C:2]1[N:3]=[CH:4][N:5]=[C:6]2[C:7]=1[N:42]=[CH:40][N:14]2[CH2:15][C:16]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=1[Cl:23]

Participants

4

Reactant 3

HCID 713FormamideHCID 24489Sodium DithioniteHCID 70525502HCID 70525502, compound

Product 1

HCID 41574ArprinocidYield 42%

Procedure

In formamide (60 ml) was suspended 4-amino-6-(2-chloro-6-fluorobenzyl)amino-5-phenylazopyrimidine (1.07 g, 3 mmols). To the suspension was added portionwise sodium dithionite (3.28 g, 15 mmols; purity 80%) with stirring at 120°-130° C. After stirring at the same temperature for 30 minutes, the mixture was stirred at 140°-150° C. for another 1 hour. The reaction mixture was concentrated to dryness under reduced pressure, the residue washed with ether (2×30 ml), and water (50 ml) added. After ice-cooling, the insoluble matter was collected by filtration and washed. This product was put in 2 N NaOH (10 ml) and the mixture was stirred at room temperature for 30 minutes. The insoluble matter was collected by filtration, dissolved in chloroform, and purified by silica gel column chromatography [100 g, eluent: chloroform and, then, chloroformmethanol (19:1)]. Recrystallization from ethanol gave 6-amino-9-(2-chloro-6-fluorobenzyl)purine as colorless crystals (350 mg, yield 42%), m.p. 249°-250° C.

Workup

  1. stirringAfter stirring at the same temperature for 30 minutes
  2. stirringthe mixture was stirred at 140°-150° C. for another 1 hour
  3. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
  4. washthe residue washed with ether (2×30 ml), and water (50 ml)
  5. additionadded
  6. temperatureAfter ice-cooling
  7. filtrationthe insoluble matter was collected by filtration
  8. washwashed
  9. stirringthe mixture was stirred at room temperature for 30 minutes
  10. filtrationThe insoluble matter was collected by filtration
  11. dissolutiondissolved in chloroform
  12. custompurified by silica gel column chromatography [100 g, eluent
  13. customRecrystallization from ethanol

Sources & evidence

ORD record
ord-a6908412601a40c391a7063cb06e8490
Source dataset
uspto-grants-1983_12
Patent number
US04423219

Reaction notes

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