Phosphorus oxychloride → HCID 178463594, compound

HRID 1976564Notes

Reaction equation

HRID 1976564 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:26]=[CH:27][C:28]=1[O:29][CH3:30])[CH2:12][N:13]1[C:21]2[N:20]=[C:19]([CH:22]([CH3:24])[CH3:23])[NH:18][C:17]=2[C:16](=O)[N:15]=[CH:14]1)C1C=CC=CC=1.P(Cl)(Cl)([Cl:33])=O>>[ClH:33].[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:26]=[CH:27][C:28]=1[O:29][CH3:30])[CH2:12][N:13]1[C:21]2[C:17]([N:18]=[C:19]([CH:22]([CH3:23])[CH3:24])[N:20]=2)=[C:16]([NH:13][CH2:21][CH3:17])[N:15]=[CH:14]1)[C:9]1[CH:10]=[CH:11][CH:26]=[CH:27][CH:28]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 9822510HCID 9822510, compound

Product 1

HCID 178463594HCID 178463594, compound

Procedure

3-(3-Benzyloxy-4-methoxy-benzyl)-8-isopropyl-hypoxanthine (2.02 g, 5 mmole) and phosphorus oxychloride (20 ml) were heated to 70° C. for 35 min. The solution was evaporated to dryness and evaporation repeated twice after the addition of toluene (50 ml). The crude chloropurine residue was dissolved in THF (20 ml) and added at 0-5° C. to 70% aqueous ethylamine (20 ml). After 1 hour at room temperature the solvents were removed in vacuo, the residue was dissolved in dichloromethane (70 ml) and washed with 1M NaOH. The organic phase was filtered through 9 g of silicagel in a column and evaporated to dryness in vacuo. The residue was dissolved in methanol (20 ml), treated with 1M methanolic HCl (4.8 ml) and evaporated to dryness in vacuo to give 3-(3-benzyloxy-4-methoxy-benzyl)-6-ethylamino-8-isopropyl-3H-purine hydrochloride (2.20 g, 94.0%), mp 79-83° C. (after crystallization from water-saturated ether).

Workup

  1. customThe solution was evaporated to dryness and evaporation
  2. additionafter the addition of toluene (50 ml)
  3. dissolutionThe crude chloropurine residue was dissolved in THF (20 ml)
  4. additionadded at 0-5° C. to 70% aqueous ethylamine (20 ml)
  5. customAfter 1 hour at room temperature the solvents were removed in vacuo
  6. dissolutionthe residue was dissolved in dichloromethane (70 ml)
  7. washwashed with 1M NaOH
  8. filtrationThe organic phase was filtered through 9 g of silicagel in a column
  9. customevaporated to dryness in vacuo
  10. dissolutionThe residue was dissolved in methanol (20 ml)
  11. additiontreated with 1M methanolic HCl (4.8 ml)
  12. customevaporated to dryness in vacuo
  13. customto give
  14. custom3-(3-benzyloxy-4-methoxy-benzyl)-6-ethylamino-8-isopropyl-3H-purine hydrochloride (2.20 g, 94.0%), mp 79-83° C. (after crystallization from water-saturated ether)

Sources & evidence

ORD record
ord-1db2c27d3f214ef6a71a393730fc794f
Source dataset
uspto-grants-2001_05
Patent number
US06228859B1

Reaction notes

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