Phosphorus oxychloride → 2-amino-6-chloro-8-methylpurine

HRID 260044Notes

Reaction equation

HRID 260044 reaction equation
[CH3:1][C:2]1[NH:10][C:9]2[C:8](=O)[NH:7][C:6]([NH2:12])=[N:5][C:4]=2[N:3]=1.P(Cl)(Cl)([Cl:15])=O>C(N(CC)C1C=CC=CC=1)C>[NH2:12][C:6]1[N:5]=[C:4]2[C:9]([NH:10][C:2]([CH3:1])=[N:3]2)=[C:8]([Cl:15])[N:7]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1354218828-Methylguanine

Product 1

HCID 120475922-amino-6-chloro-8-methylpurine

Reagents, catalysts & solvents 1

HCID 7061N,N-DiethylanilineSolvent

Procedure

A suspension of 8-methylguanine (Daves et al., J. Am. Chem. Soc., 82, 2633-2640 (1960)) (1.0 g, 6.1 mmol) in phosphorous oxychloride (30 mL) and N,N-diethylaniline (1 mL) was refluxed for 3 h. The excess phosphorous oxychloride was evaporated under reduced pressure. The resulting brown oil was dissolved in ice-water and was neutralized with a concentrated aqueous NaOH solution. After evaporation of the solvent, the solid residue was suspended in 70 mL of H2O. Undissolved solid was filtered off, and the filtrate was loaded on a 3×80 cm Sephadex LH-20 column eluted with methanol/water (1:1) at 1 mL/min. Column eluent was continuously monitored at 280 nm and fractions (10 mL) were collected. Evaporation of pooled fractions 50-60 produced 2-amino-6-chloro-8-methylpurine as a crude solid. Crystallization from ethanol/water with charcoal treatment afforded 2-amino-6-chloro-8-methylpurine as a white solid: yield, 0.57 g (51%); mp >265° C. dec.; 1H NMR δ2.39 (s, 3H, CH3), 6.62 (s, 2H, NH2, exchange with D2O), 12.56 (s, 1H, NH, exchanges with D2O); MS (EI) calcd. m/z for C6H6N535Cl 183.0312, found 183.0309; calcd. m/z for C6H6N537Cl 185.0283, found 185.0286.

Workup

  1. temperaturewas refluxed for 3 h
  2. customThe excess phosphorous oxychloride was evaporated under reduced pressure
  3. dissolutionThe resulting brown oil was dissolved in ice-water
  4. customAfter evaporation of the solvent
  5. filtrationwas filtered off
  6. washcolumn eluted with methanol/water (1:1) at 1 mL/min
  7. customwere collected
  8. customEvaporation of pooled fractions 50-60 produced 2-amino-6-chloro-8-methylpurine as a crude solid
  9. customCrystallization from ethanol/water with charcoal treatment

Sources & evidence

ORD record
ord-9b1573b1972d47dc80931d541062b5b5
Source dataset
uspto-grants-1996_06
Patent number
US05525606

Reaction notes

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