Phosphorus oxychloride → HCID 15896244, compound

HRID 1290875Notes

Reaction equation

HRID 1290875 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]1[NH:11][C:10]2[C:9](=O)[NH:8][C:7]([NH2:13])=[N:6][C:5]=2[N:4]=1.P(Cl)(Cl)([Cl:18])=O>>[NH2:13][C:7]1[N:6]=[C:5]2[C:10]([NH:11][C:3]([C:2]([F:15])([F:14])[F:1])=[N:4]2)=[C:9]([Cl:18])[N:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 135709864HCID 135709864, compound

Product 1

HCID 15896244HCID 15896244, compound

Procedure

A suspension of 8-trifluoromethylguanine (Pfleiderer and Shanshal, Liebigs Ann. Chem., 726, 201-215 (1969)) (2.0 g, 9.1 mmol) in phosphorous oxychloride (20 mL) was refluxed for 3 h. Excess phosphorous oxychloride was evaporated under reduced pressure. The resulting residue was mixed with ice-water (100 g), and the pH was adjusted to 3-4 with a concentrated aqueous NaOH solution. The resulting solution was mixed with MeOH (100 mL) and approximately half (i.e., 100 mL) of the aqueous methanol solution 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. The remainder of the reaction mixture in MeOH/H2O was chromatographed separately under identical conditions. The desired product eluted in fractions 73-85. Evaporation of solvent from the pooled fractions 73-85 from both chromatographic runs afforded analytically pure 2-amino-6-chloro-8-trifluoromethylpurine: yield, 0.94 g (43%); mp >225° C. dec.; UV (pH 1) λmax 245 nm (ε=0.501×104), 314 (0.746×104); (pH 6.9) 270 (0.265×104), 315 (0.612×104); (pH 13) 272 (0.269×104), 314 (0.612×104); 1H NMR δ7.19 (s, 2H, NH2, exchange with D2O), 14.25 (br s, 1H, NH, exchanges with D2O); MS (EI) calcd. m/z for C6H3 N5F335Cl237.0029, found 237.0011; calcd. m/z for C6 H3N F 37Cl 239.0000, found 238.9987; Anal. (C6H3 N5F3C) C, H, N, F, Cl.

Workup

  1. temperaturewas refluxed for 3 h
  2. customExcess phosphorous oxychloride was evaporated under reduced pressure
  3. additionThe resulting residue was mixed with ice-water (100 g)
  4. additionThe resulting solution was mixed with MeOH (100 mL) and approximately half (i.e., 100 mL) of the aqueous methanol solution
  5. washcolumn eluted with methanol/water (1:1) at 1 mL/min
  6. customwere collected
  7. customThe remainder of the reaction mixture in MeOH/H2O was chromatographed separately under identical conditions
  8. washThe desired product eluted in fractions 73-85
  9. customEvaporation of solvent from the pooled fractions 73-85 from both chromatographic runs

Sources & evidence

ORD record
ord-3b041cc9d43f449a8ec94b6929df45fd
Source dataset
uspto-grants-1998_05
Patent number
US05753668

Reaction notes

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