Water → HCID 118020764, compound

HRID 1777387Notes

Reaction equation

HRID 1777387 reaction equation
[OH:1][NH:2][C:3](=[NH:10])[CH2:4][CH:5]([O:8][CH3:9])[O:6][CH3:7].[F:11][C:12]1[CH:13]=[CH:14][C:15]([C:18](O)=O)=[N:16][CH:17]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.O>CN(C=O)C>[CH3:7][O:6][CH:5]([O:8][CH3:9])[CH2:4][C:3]1[N:10]=[C:18]([C:15]2[CH:14]=[CH:13][C:12]([F:11])=[CH:17][N:16]=2)[O:1][N:2]=1

Participants

6

Reactant 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 27628765-fluoropyridine-2-carboxylic AcidHCID 178495319HCID 178495319, compound

Product 1

HCID 118020764HCID 118020764, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
40 °C

Procedure

A solution of N-hydroxy-3,3-dimethoxypropanimidamide obtained in Reference Example 19 (1.0 g, 6.8 mmol) in DMF (3 mL) was added to a solution of 5-fluoropyridine-2-carboxylic acid (1.0 g, 7.1 mmol) and carbonyldiimidazole (1.3 g, 8.1 mmol) in DMF (4 mL), which was stirred for 1 hour at 40° C., and the mixture was stirred for 30 minutes. The reaction solution was heated to 90° C. and stirred for 15 hours. Water was added to the reaction mixture, followed by extraction with EtOAc. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, dried over Na2SO4, then the drying agent was filtered off, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (HP-Sil 25 g, hexane/EtOAc=75/25 to 0/100) to obtain the title compound (1.2 g) (colorless solid).

Workup

  1. stirringthe mixture was stirred for 30 minutes
  2. temperatureThe reaction solution was heated to 90° C.
  3. stirringstirred for 15 hours
  4. extractionfollowed by extraction with EtOAc
  5. washThe organic layer was washed with water
  6. dry with materiala saturated aqueous solution of sodium chloride, dried over Na2SO4
  7. filtrationthe drying agent was filtered off
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe obtained residue was purified by column chromatography (HP-Sil 25 g, hexane/EtOAc=75/25 to 0/100)

Sources & evidence

ORD record
ord-d687d270f0fb466f860fb964c84f1e93
Source dataset
uspto-grants-2016_02
Patent number
US09266870B2

Reaction notes

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