Ammonia → HCID 178490822, compound

HRID 1976565Notes

Reaction equation

HRID 1976565 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)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:33])=O.[NH3:36].Cl>CO>[ClH:33].[NH2:36][C:16]1[N:15]=[CH:14][N:13]([CH2:12][C:11]2[CH:26]=[CH:27][C:28]([O:29][CH3:30])=[C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:10]=2)[C:21]2[C:17]=1[N:18]=[C:19]([CH:22]([CH3:24])[CH3:23])[N:20]=2

Participants

6

Reactant 4

HCID 222Ammonia2×HCID 313Hydrochloric AcidHCID 24813Phosphorus oxychlorideHCID 9822510HCID 9822510, compound

Product 1

HCID 178490822HCID 178490822, compoundYield 91.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

3-(3-Benzyloxy-4-methoxy-benzyl)-8-isopropyl-hypoxanthine (Example 6C) (4.04 g, 10 mmole) and phosphorus oxychloride (40 ml) were heated to 70° C. for 35 minutes. The reaction mixture was evaporated to dryness in vacuo and, after the addition of toluene, evaporation repeated twice. The crude chloropurine was dissolved in THF (40 ml) and added slowly with cooling to 32% aqueous ammonia (12 ml, 200 mmole) in a 450 ml pressure reactor. After the addition of liquid ammonia (50 g) at −30° C. the mixture was heated to 60° C. (340 psi) for 3 hours. The solid was filtered off and the solution evaporated to dryness in vacuo. The residue was suspended in water (100 ml) and the mixture filtered to give the crude product (4.09 g) as a crystalline solid. This was dissolved in methanol (60 ml), treated with 1M methanolic HCl solution (10 ml), evaporated to dryness in vacuo, suspended in acetone and filtered to give 6-amino-3-(3-benzyloxy-4-methoxy-benzyl)-8-isopropyl-3H-purine hydrochloride (4.04 g, 91.8%), as a crystalline solid mp 200° C., (sublimation)/240-243° C.

Workup

  1. customThe reaction mixture was evaporated to dryness in vacuo
  2. additionafter the addition of toluene, evaporation
  3. dissolutionThe crude chloropurine was dissolved in THF (40 ml)
  4. additionadded slowly
  5. filtrationThe solid was filtered off
  6. customthe solution evaporated to dryness in vacuo
  7. filtrationthe mixture filtered
  8. customto give the crude product (4.09 g) as a crystalline solid
  9. customevaporated to dryness in vacuo
  10. filtrationfiltered

Sources & evidence

ORD record
ord-f223217fe02c494cb0ac0604fe2d9b92
Source dataset
uspto-grants-2001_05
Patent number
US06228859B1

Reaction notes

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