Hydrochloric Acid → 5-Chloro-8-[(6-methoxy-pyridin-3-yl)-methyl]-[1,6]naphthyridine

HRID 49229Notes

Reaction equation

HRID 49229 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([CH2:9][C:10]2[C:19]3[N:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:13](=O)[NH:12][CH:11]=2)=[CH:5][CH:4]=1.P(Cl)(Cl)([Cl:23])=O.Cl>C(#N)C.O1CCOCC1>[Cl:23][C:13]1[N:12]=[CH:11][C:10]([CH2:9][C:6]2[CH:7]=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[C:19]2[C:14]=1[CH:15]=[CH:16][CH:17]=[N:18]2

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 24813Phosphorus oxychlorideHCID 20636431HCID 20636431, compound

Product 1

HCID 206364295-Chloro-8-[(6-methoxy-pyridin-3-yl)-methyl]-[1,6]naphthyridine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Procedure

396 mg (1.48 mmol) of 8-[(6-methoxy-pyridin-3-yl)-methyl]-6H-[1,6]naphthyridin-5-one in 24 ml of acetonitrile are mixed, whilst excluding air, with 1.4 ml (15 mmol) of phosphorus oxychloride and 0.78 ml of 4 N HCl in dioxane and stirred for 96 h at 65° C. After cooling to RT, partial concentration by evaporation takes place on a RE, then 40 ml of ice water and 10 ml of NH3 solution are added and extraction carried out 3 times with EtOAc. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated by evaporation to form 5-chloro-8-[(6-methoxy-pyridin-3-yl)-methyl]-[1,6]naphthyridine (contaminated with a little 5-chloro-8-[(6-chloro-pyridin-3-yl)-methyl]-[1,6]naphthyridine); FAB-MS: (M+H)+=286; HPLC(gradient20-100) tRet=10.2.

Workup

  1. concentrationpartial concentration
  2. customby evaporation
  3. additionare added
  4. extractionextraction
  5. washThe organic phases are washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-b832b55a3c81463b862bbbabb19fb4e7
Source dataset
uspto-grants-2004_03
Patent number
US06706731B2

Reaction notes

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