Phosphorus oxychloride → HCID 86661440, compound

HRID 474325Notes

Reaction equation

HRID 474325 reaction equation
O=[C:2]1[N:7]=[CH:6][N:5]2[N:8]=[CH:9][C:10]([C:11]([OH:13])=O)=[C:4]2[CH2:3]1.P(Cl)(Cl)([Cl:16])=O.[CH:19]([N:22](CC)C(C)C)([CH3:21])[CH3:20]>>[Cl:16][C:2]1[N:7]=[CH:6][N:5]2[N:8]=[CH:9][C:10]([C:11]([NH:22][CH:19]([CH3:21])[CH3:20])=[O:13])=[C:4]2[CH:3]=1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 66677260HCID 66677260, compound

Product 1

HCID 86661440HCID 86661440, compoundYield 90%

Procedure

A mixture of 5-oxo-4,5-dihydropyrazolo[1,5-c]pyrimidine-3-carboxylic acid (2.0 g, 10 mM, 1.0 equiv), 30 mL of phosphorus oxychloride (300 mM, 30 equiv) and N,N-diisopropylethylamine (8 mL, 40 mM, 4 equiv) was heated with stirring to reflux for 2 hours. The reaction mixture was cooled and concentrated under vacuum. The brown oil was taken up in dichloromethane and isopropylamine added (3 mL, 30 mM, 3 equiv). The reaction mixture was stirred 5 minutes then partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over sodium sulfate and vacuum filtered through a pad of silica gel. The filtrate was concentrated and cooled and the crystallized product collected by filtration to give 2.31 g (90%) of 5-chloro-N-isopropylpyrazolo[1,5-c]pyrimidine-3-carboxamide. LCMS (ESI) m+H=239.1 (mono chlorinated isotope pattern) 1H NMR (400 MHz, DMSO-d6) δ: 9.33 (d, 1H), 8.60 (s, 1H), 7.47 (d, 1H), 7.36 (d, 1H), 4.09 (m, 1H), 1.20 (d, 6H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2 hours
  3. temperatureThe reaction mixture was cooled
  4. concentrationconcentrated under vacuum
  5. additionisopropylamine added (3 mL, 30 mM, 3 equiv)
  6. stirringThe reaction mixture was stirred 5 minutes
  7. customthen partitioned between ethyl acetate and water
  8. washThe organic phase was washed with brine
  9. dry with materialdried over sodium sulfate and vacuum
  10. filtrationfiltered through a pad of silica gel
  11. concentrationThe filtrate was concentrated
  12. temperaturecooled
  13. filtrationthe crystallized product collected by filtration

Sources & evidence

ORD record
ord-31a8d0daef10414b8a2e8e1ae57b9edf
Source dataset
uspto-grants-2014_01
Patent number
US08637526B2

Reaction notes

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