N,N-Dimethylaniline → HCID 178431609, compound

HRID 2220135Notes

Reaction equation

HRID 2220135 reaction equation
[OH:1][C:2]1[C:7]([CH3:8])=[C:6](O)[N:5]2[N:10]=[CH:11][CH:12]=[C:4]2[C:3]=1[C:13]#[N:14].CN(C)C1C=CC=CC=1.P(Cl)(Cl)([Cl:26])=O>>[Cl:26][C:6]1[N:5]2[N:10]=[CH:11][CH:12]=[C:4]2[C:3]([C:13]#[N:14])=[C:2]([OH:1])[C:7]=1[CH3:8]

Participants

4

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 178431610HCID 178431610, compound

Product 1

HCID 178431609HCID 178431609, compound

Procedure

To the crude product (378 mg) of 5,7-dihydroxy-6-methylpyrazolo[1,5-a]pyridine-4-carbonitrile (5), N,N-dimethylaniline (380 μL) was added and this mixture was suspended in phosphoryl chloride (20 mL). This suspension was stirred under reflux with heating for 3 h. After the reaction solution was cooled to room temperature, excessive phosphoryl chloride was removed under reduced pressure. The residue was diluted with ethyl acetate and water, and two layers were separated. The organic layer was reversely extracted with saturated aqueous sodium hydrogen carbonate solution, and the aqueous extract was combined with the aqueous layer. The pH of combined aqueous layers were adjusted to 10 with 2 mol/L aqueous sodium hydroxide solution, and the solution was stirred for 4 days. This mixture was acidified to pH 2 with 1 mol/L hydrochloric acid and extracted with ethyl acetate three times. The combined organic layers were washed with a mixture of brine and 1 mol/L hydrochloric acid (5:1) and dried over sodium sulfate. The solvent was removed under reduced pressure to obtain the title compound (13) (211 mg), a part of which was purified with preparative HPLC and the NMR spectrum was recorded.

Workup

  1. temperatureunder reflux
  2. temperaturewith heating for 3 h
  3. customexcessive phosphoryl chloride was removed under reduced pressure
  4. additionThe residue was diluted with ethyl acetate and water, and two layers
  5. customwere separated
  6. extractionThe organic layer was reversely extracted with saturated aqueous sodium hydrogen carbonate solution
  7. extractionthe aqueous extract
  8. stirringthe solution was stirred for 4 days
  9. extractionextracted with ethyl acetate three times
  10. washThe combined organic layers were washed with a mixture of brine and 1 mol/L hydrochloric acid (5:1)
  11. dry with materialdried over sodium sulfate
  12. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-7767743a426747f2b39604c0d59dd960
Source dataset
uspto-grants-2008_08
Patent number
US07417053B2

Reaction notes

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