Potassium Phosphate, Tribasic → HCID 17218092, compound

HRID 1754343Notes

Reaction equation

HRID 1754343 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[F:9][C:10]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:11]=1[C:12]([NH2:14])=[O:13].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C)CCN>O1CCOCC1.[Cu](I)I>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([NH:14][C:12](=[O:13])[C:11]2[C:10]([F:9])=[CH:18][CH:17]=[CH:16][C:15]=2[F:19])=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 66053N,N-DimethylethylenediamineHCID 874392,6-DifluorobenzamideHCID 27344145-Bromo-2-chloropyridine

Product 1

HCID 17218092HCID 17218092, compoundYield 63.9%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of 2-chloro-5-bromopyridine (370 mg, 1.9 mmol, 1.2 eq) and 2,6-difluorobenzamide (250 mg, 1.5 mmol, 1.0 eq) in dioxane (10 mL), copper iodide (151 mg, 0.75 mmol, 0.5 eq), potassium phosphate (670 mg, 3.15 mmol, 2.1 eq) and N,N-dimethylethylene diamine (0.1 mL, 1.05 mmol, 0.7 eq) were added sequentially. The resulting mixture was stirred at reflux for 15 h. The reaction was cooled to room temperature, filtered to remove the solid components and the filtrate was concentrated under vacuum. The residue was dissolved in ethyl acetate (50 mL), washed with water (20 mL), brine (20 mL), dried (Na2SO4) and filtered. The filtrate was concentrated under vacuum and the crude product was purified by flash column chromatography (silica gel, ethyl acetate and hexane) to afford 300 mg of the solid product as a white solid. 1HNMR (400 MHz, DMSO-d6) δ 11.22 (s, 1H, D2O exchangeable), 8.70 (d, J=2.5 Hz, 1H), 8.18 (dd, J=8.0, 2.5 Hz, 1H), 7.67-7.59 (m, 1H), 7.55 (d, J=8.0 Hz, 1H), 7.29 (t, J=8.0 Hz, 2H); ESI-MS (m/z) 313, 315 [(MH)+ Br79,81].

Workup

  1. additionwere added sequentially
  2. temperatureat reflux for 15 h
  3. filtrationfiltered
  4. customto remove the solid components
  5. concentrationthe filtrate was concentrated under vacuum
  6. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
  7. washwashed with water (20 mL), brine (20 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under vacuum
  11. customthe crude product was purified by flash column chromatography (silica gel, ethyl acetate and hexane)

Sources & evidence

ORD record
ord-876a1f56260c43c98702942288b7a5b7
Source dataset
uspto-grants-2015_10
Patent number
US09169242B2

Reaction notes

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