Phosphorus oxychloride → 4-Chloro-1,5-naphthyridine-3-carbonitrile

HRID 869447Notes

Reaction equation

HRID 869447 reaction equation
O[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][N:10]=2)[N:5]=[CH:4][C:3]=1[C:12]#[N:13].O=P(Cl)(Cl)[Cl:16]>>[Cl:16][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][N:10]=2)[N:5]=[CH:4][C:3]=1[C:12]#[N:13]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178510307HCID 178510307, compound

Product 1

HCID 185489474-Chloro-1,5-naphthyridine-3-carbonitrile

Procedure

A mixture of 4-hydroxy-1,5-naphthyridine-3-carbonitrile (C-4) (2.0 g, 11.7 mmol, 1.0 eq) in phosphoroxychloride (40 mL, 424 mol, 36.2 eq) is stirred at reflux for 3 h. The mixture is cooled to RT and concentrated in vacuo. The residue is poured into ice-water (50 mL) and neutralized with saturated aqueous NaHCO1 solution to adjust the pH to 8 while keeping the temperature below 5° C. The mixture is extracted with DCM (3×50 mL). The combined organic layer is 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 (1.25% MeOH-DCM) to afford the product, 4-chloro-1,5-naphthyridine-3-carbonitrile (C-5).

Workup

  1. temperatureat reflux for 3 h
  2. concentrationconcentrated in vacuo
  3. additionThe residue is poured into ice-water (50 mL)
  4. customthe temperature below 5° C
  5. extractionThe mixture is extracted with DCM (3×50 mL)
  6. washThe combined organic layer is washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationThe filtrate is concentrated in vacuo
  10. customthe residue is purified by flash column chromatography on silica gel (1.25% MeOH-DCM)

Sources & evidence

ORD record
ord-0f6588348dea426fa1674db7c9d34893
Source dataset
uspto-grants-2015_03
Patent number
US08969363B2

Reaction notes

Loading…