Phosphorus oxychloride → 8-Chloro-2-methyl-1,7-naphthyridine

HRID 1787657Notes

Reaction equation

HRID 1787657 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[CH:8]=[CH:7][NH:6][C:5](=O)[C:4]=2[N:3]=1.P(Cl)(Cl)([Cl:15])=O>>[Cl:15][C:5]1[N:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[N:3]=[C:2]([CH3:1])[CH:11]=[CH:10]2

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 22090499HCID 22090499, compound

Product 1

HCID 576003498-Chloro-2-methyl-1,7-naphthyridine

Conditions

Temperature
90 °C

Procedure

A suspension of 2-Methyl-7H-[1,7]naphthyridin-8-one (820 mg, 5.12 mmol) and phosphorus oxychloride (7 ml, 76.8 mmol) was stirred at 90° C. for 4 hours. The reaction mixture was evaporated to dryness, poured on ice and set alkaline with aqueous ammonia. A red solution resulted. The aqueous layer was extracted with dichloromethane (three times). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (ethyl acetate/heptane 0:100->20:80 gradient). The desired compound was obtained as a white solid (810 mg, 89%), MS: m/e=(M+H+).

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. additionpoured on ice and set alkaline with aqueous ammonia
  3. customA red solution resulted
  4. extractionThe aqueous layer was extracted with dichloromethane (three times)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography on silica gel (ethyl acetate/heptane 0:100->20:80 gradient)

Sources & evidence

ORD record
ord-aa36a447ff8b4421940d3e4f44879bc2
Source dataset
uspto-grants-2009_03
Patent number
US07511055B2

Reaction notes

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