N,N-Dimethylaniline → 7-CHLOROPYRAZOLO[1,5-A]PYRIMIDINE

HRID 1051755Notes

Reaction equation

HRID 1051755 reaction equation
[N:1]1[N:5]2[C:6](O)=[CH:7][CH:8]=[N:9][C:4]2=[CH:3][CH:2]=1.O=P(Cl)(Cl)[Cl:13].CN(C)C1C=CC=CC=1>>[Cl:13][C:6]1[N:5]2[N:1]=[CH:2][CH:3]=[C:4]2[N:9]=[CH:8][CH:7]=1

Participants

4

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 178516450HCID 178516450, compound

Product 1

HCID 122816477-CHLOROPYRAZOLO[1,5-A]PYRIMIDINE

Procedure

To a solution of pyrazolo[1,5-a]pyrimidin-7-ol (C-1) (19.0 g, 14.1 mmol, 1.0 eq) in phosphoroxychloride (100 mL, 1.06 mol, 76 eq) at RT, N,N-dimethylaniline (7.0 g, 58.0 mmol, 4.1 eq) is added dropwise and the resulting mixture is stirred at reflux overnight. The mixture is allowed to cool to RT and concentrated in vacuo to remove the phosphoroxychloride. The residue is poured into ice water (200 mL), neutralized with saturated aqueous NaHCO3 solution to adjust the pH to 8-9 while keeping the temperature below 5° C. The mixture is stirred at RT for 30 min and then extracted with ethyl acetate (4×200 mL). The combined organic layers are washed with brine, dried over Na2SO4 and filtered. The filtrate is concentrated in vacuo and the residue is purified by flash column chromatography on silica gel (1-3% ethyl acetate-petroleum ether) to afford the product, 7-chloropyrazolo[1,5-a]pyrimidine (C-2).

Workup

  1. temperatureat reflux overnight
  2. concentrationconcentrated in vacuo
  3. customto remove the phosphoroxychloride
  4. additionThe residue is poured into ice water (200 mL)
  5. customthe temperature below 5° C
  6. stirringThe mixture is stirred at RT for 30 min
  7. extractionextracted with ethyl acetate (4×200 mL)
  8. washThe combined organic layers are washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationThe filtrate is concentrated in vacuo
  12. customthe residue is purified by flash column chromatography on silica gel (1-3% ethyl acetate-petroleum ether)

Sources & evidence

ORD record
ord-e5ea8f5600b74869b4dbe6ffdc1bd89d
Source dataset
uspto-grants-2016_07
Patent number
US09388183B2

Reaction notes

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