Hydrochloric Acid → HCID 25055215, compound

HRID 1513029Notes

Reaction equation

HRID 1513029 reaction equation
Cl[C:2]1[N:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1C(O)=O.Cl.[F:13][C:14]1[CH:20]=[C:19]([O:21][CH3:22])[C:18]([O:23][CH2:24][C:25]2[C:30]([O:31][CH3:32])=[CH:29][CH:28]=[C:27]([F:33])[C:26]=2[F:34])=[CH:17][C:15]=1[NH2:16].[H-].[Na+].Cl.C[N:39]1CCC[C:40]1=[O:44]>>[Cl:11][C:9]1[N:10]=[C:2]2[N:16]([C:15]3[CH:17]=[C:18]([O:23][CH2:24][C:25]4[C:30]([O:31][CH3:32])=[CH:29][CH:28]=[C:27]([F:33])[C:26]=4[F:34])[C:19]([O:21][CH3:22])=[CH:20][C:14]=3[F:13])[C:40](=[O:44])[NH:39][C:3]2=[CH:7][CH:8]=1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 13387N-methyl-2-pyrrolidoneHCID 24758Sodium hydrideHCID 8540472,6-Dichloronicotinic acidHCID 68511734HCID 68511734, compound

Product 1

HCID 25055215HCID 25055215, compound

Conditions

Temperature
120 °C

Procedure

To a mixture of 2,6-dichloronicotinic acid (0.58 g) and 2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyaniline hydrochloride (0.7 g) in 1-methyl-2-pyrrolidone (4 mL) was added sodium hydride (55%, 0.35 g), and the mixture was stirred at 120° C. overnight. The reaction mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residual solids were suspended in a mixed solvent (n-hexane/ethyl acetate=2/1), and collected by filtration. The collected solids were washed with the same solvent, and dried under reduced pressure. To the obtained solids were added 1,4-dioxane (5 mL), triethylamine (0.31 mL) and diphenylphosphoryl azide (0.24 mL), and the mixture was stirred at room temperature for 1 hour, and then heated at reflux for 4 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/1−1/3) to give the title compound (0.16 g).

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. washThe extract was washed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was removed under reduced pressure
  5. filtrationcollected by filtration
  6. washThe collected solids were washed with the same solvent
  7. customdried under reduced pressure
  8. additionTo the obtained solids were added 1,4-dioxane (5 mL), triethylamine (0.31 mL) and diphenylphosphoryl azide (0.24 mL)
  9. stirringthe mixture was stirred at room temperature for 1 hour
  10. temperatureheated
  11. temperatureat reflux for 4 hours
  12. concentrationThe reaction mixture was concentrated under reduced pressure
  13. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/1−1/3)

Sources & evidence

ORD record
ord-4e085f1d8d444e12ae371898112aabc6
Source dataset
uspto-grants-2012_07
Patent number
US08217069B2

Reaction notes

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