Hydrochloric Acid → HCID 67503344, compound

HRID 219291Notes

Reaction equation

HRID 219291 reaction equation
Br.[OH:2][C:3]1[CH:4]=[N:5][C:6]2[CH:7]=[CH:8][N:9]([CH:14]([CH3:18])[C:15]([OH:17])=[O:16])[C:10](=[O:13])[C:11]=2[CH:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)S(O[CH2:31][C:32]([F:35])([F:34])[F:33])(=O)=O.CN(C)C=O.[ClH:43]>CCOC(C)=O>[ClH:43].[O:13]=[C:10]1[N:9]([CH:14]([CH3:18])[C:15]([OH:17])=[O:16])[CH:8]=[CH:7][C:6]2[N:5]=[CH:4][C:3]([O:2][CH2:31][C:32]([F:35])([F:34])[F:33])=[CH:12][C:11]1=2

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 67503082HCID 67503082, compound

Product 1

HCID 67503344HCID 67503344, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A resealable pressurized vial was charged with 2-(3-hydroxy-5-oxo-1,6-naphthyridin-6(5H)-yl)propanoic acid hydrobromide (0.54 g, 2 mmol), cesium carbonate (2 g, 7 mmol), 2,2,2-trifluoroethyl trifluoromethanesulfonate (2 g, 7 mmol), and N,N-dimethylformamide (6 mL, 0.3M). The vessel was sealed and the mixture was stirred at 60° C. for 1 hr. The reaction mixture was diluted with EtOAc and washed with water. The organic layer was collected, dried over sodium sulfate, and concentrated under reduced pressure to afford brown oil. This was purified via MPLC (10-50% EtOAC/Hexanes) to afford tan solid of bis alkylated material. This was suspended and refluxed in 5 mL of 6N HCl for 2 hours. Reaction mixture concentrated and dried under reduced pressure to afford 2-(5-oxo-3-(2,2,2-trifluoroethoxy)-1,6-naphthyridin-6(5H)-yl)propanoic acid hydrochloride (0.3 g, 50% yield). This was concentrated under reduced pressure to dryness to afford 2-(5-oxo-3-(2,2,2-trifluoroethoxy)-1,6-naphthyridin-6(5H)-yl)propanoic acid hydrochloride (0.3 g, 50% yield) as yellow solid. Free base material MS m/z=317.0 [M+1]+. Calc'd for C13H12ClF3N2O4: 352.7.

Workup

  1. customThe vessel was sealed
  2. washwashed with water
  3. customThe organic layer was collected
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto afford brown oil
  7. customThis was purified via MPLC (10-50% EtOAC/Hexanes)
  8. customto afford tan solid of bis
  9. customReaction mixture
  10. concentrationconcentrated
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-4511f11690564d989086a965baaaede4
Source dataset
uspto-grants-2012_06
Patent number
US08198448B2

Reaction notes

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