N,N-Dimethylaniline → 4-Chloro-1H-pyrazolo[3,4-d]pyrimidine

HRID 1931603Notes

Reaction equation

HRID 1931603 reaction equation
P(Cl)(Cl)([Cl:3])=O.[CH:6]1[C:7]2[C:14](=O)[NH:13][CH:12]=[N:11][C:8]=2[NH:9][N:10]=1.CN(C)C1C=CC=CC=1>>[Cl:3][C:14]1[N:13]=[CH:12][N:11]=[C:8]2[NH:9][N:10]=[CH:6][C:7]=12

Participants

4

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 135401907Allopurinol

Product 1

HCID 2210954-Chloro-1H-pyrazolo[3,4-d]pyrimidineYield 56.1%

Procedure

Phosphorus oxychloride (300 mL, 3.2 mol) was added to allopurinol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 20 g, 0.15 mol) and then N,N-dimethylaniline (30 mL, 0.24 mol) was added at room temperature. The resulting mixture was heated at reflux for 90 min and then cooled. The solvent was removed under vacuum. The residue was co-evaporated twice with toluene, and the resulting dark colored syrup was poured into a mixture of ice and water (500 mL). The mixture was stirred for 15 min, then transferred to a separatory funnel and extracted with ether (4×500 mL) and ethyl acetate (2×500 mL). The combined organic layers were washed twice with ice-water, dried (sodium sulfate), and concentrated to approximately 1.5 L. Charcoal was added to the slightly purple solution and the mixture was filtered through Celite. The Celite was washed with ethyl acetate and the combined filtrates were evaporated to dryness to give 4-chloro-1H-pyrazolo[3,4-d]pyrimidine (13 g, 56%) as a pale green solid. 1H NMR (300 MHz, DMSO-d6) δ 8.44 (s, 1H), 8.81 (s, 1H), 14.50 (br s, 1H).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 90 min
  3. temperaturecooled
  4. customThe solvent was removed under vacuum
  5. additionthe resulting dark colored syrup was poured into a mixture of ice and water (500 mL)
  6. customtransferred to a separatory funnel
  7. extractionextracted with ether (4×500 mL) and ethyl acetate (2×500 mL)
  8. washThe combined organic layers were washed twice with ice-water
  9. dry with materialdried (sodium sulfate)
  10. concentrationconcentrated to approximately 1.5 L
  11. additionCharcoal was added to the slightly purple solution
  12. filtrationthe mixture was filtered through Celite
  13. washThe Celite was washed with ethyl acetate
  14. customthe combined filtrates were evaporated to dryness

Sources & evidence

ORD record
ord-a8b00a5a851e4c98a6f6dfc04b3c302a
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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