Phosphorus oxychloride → 4-Chloro-1H-pyrazolo[3,4-d]pyrimidine

HRID 2194475Notes

Reaction equation

HRID 2194475 reaction equation
[CH:1]1[C:2]2[C:9](=O)[NH:8][CH:7]=[N:6][C:3]=2[NH:4][N:5]=1.P(Cl)(Cl)([Cl:13])=O.C(N(C(C)C)CC)(C)C>C1(C)C=CC=CC=1>[Cl:13][C:9]1[N:8]=[CH:7][N:6]=[C:3]2[NH:4][N:5]=[CH:1][C:2]=12

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 135401907Allopurinol

Product 1

HCID 2210954-Chloro-1H-pyrazolo[3,4-d]pyrimidineYield 70.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of allopurinol (20 g; 146.94 mmoles) in toluene (205.71 mL), add phosphoryl chloride (68.27 mL; 734.68 mmoles) and diisopropylethylamine (56.38 mL; 323.26 mmoles) and heat the mixture at 80° C. for 2 hours. Remove the solvent in vacuo to half and pour the mixture into 2 M potassium phosphate, dibasic (734.68 mL; 1.47 moles) in water at 4° C. Stir the mixture overnight at room temperature (RT). Filter off the precipitate through a pad of Celite® and wash it subsequently with EtOAc. Separate the filtrate, wash the aqueous layer with more EtOAc, join the organic layers, dry it over MgSO4, filter and concentrate in vacuo to afford the title compound (16 g; 70.45% yield) as a yellow solid. MS (APCI): m/z=155.1 [M+H].

Workup

  1. customRemove the solvent in vacuo to half
  2. additionpour the mixture into 2 M potassium phosphate, dibasic (734.68 mL; 1.47 moles) in water at 4° C
  3. filtrationFilter off the precipitate through a pad of Celite®
  4. washwash it subsequently with EtOAc
  5. customSeparate the filtrate
  6. washwash the aqueous layer with more EtOAc
  7. dry with materialdry it over MgSO4
  8. filtrationfilter
  9. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-b63669ddaf0c4541a42263b9930dd765
Source dataset
uspto-grants-2012_12
Patent number
US08334293B2

Reaction notes

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