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

HRID 1804532Notes

Reaction equation

HRID 1804532 reaction equation
O[C:2]1[N:7]=[CH:6][N:5]=[C:4]2[NH:8][N:9]=[CH:10][C:3]=12.CN(C)C1C=CC=CC=1.O=P(Cl)(Cl)[Cl:22]>>[Cl:22][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[NH:8][N:9]=[CH:10][C:3]=12

Participants

4

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 178518059HCID 178518059, compound

Product 1

HCID 2210954-Chloro-1H-pyrazolo[3,4-d]pyrimidine

Procedure

To a mixture of commercially available 4-hydroxypyrazolo[3,4-d]pyrimidine (78) (Acros, 14.5 g, 106.5 mmol) stirred in POCl3 (375 mL) was added N,N-dimethylaniline (21 mL). The mixture was refluxed for 1.5 h. After cooling, excess POCl3 was removed by rotarty evaporation and pumped on high vacuum before pouring over 500 mL ice while stirring. The mixture was stirred for 10 min before extracting with ethyl ether (6×250 mL). The combined organic layer was washed with ice water (3×100 mL) and dried over MgSO4 and filtered. The ethyl ether was stripped and the resulting pale yellow solid (10 g, 61%) was pumped on high vacuum overnight. Compound 79: mp>300° C., dec. 125° C.; MS (ES+ calculated: 154.56; found: 156.21 M+H). HPLC (98% purity, retention time 6.033 minutes—method D) 1H NMR (400 MHz, DMSO-d6) δ 14.55 (bs, 1H), 8.84 (s, 1H), 8.46 (s, 1H).

Workup

  1. temperatureThe mixture was refluxed for 1.5 h
  2. temperatureAfter cooling
  3. customexcess POCl3 was removed by rotarty evaporation
  4. additionbefore pouring over 500 mL ice
  5. stirringThe mixture was stirred for 10 min
  6. extractionbefore extracting with ethyl ether (6×250 mL)
  7. washThe combined organic layer was washed with ice water (3×100 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customwas pumped on high vacuum overnight
  11. custom125° C.

Sources & evidence

ORD record
ord-a9a5039f25124f33b0d013d8a57b7032
Source dataset
uspto-grants-2013_01
Patent number
US08354414B2

Reaction notes

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