Trifluoroacetic anhydride → N-{3-[(2-aminoimidazo[1,2-a]pyridin-6-yl)oxy]phenyl}-6-methylpyridine-2-carboxamide

HRID 1874547Notes

Reaction equation

HRID 1874547 reaction equation
[NH2:1][C:2](=O)[CH2:3][N:4]1[C:9](=[N:10]S(C2C=CC(C)=CC=2)(=O)=O)[CH:8]=[CH:7][C:6]([O:21][C:22]2[CH:23]=[C:24]([NH:28][C:29]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[N:32]=3)=[O:30])[CH:25]=[CH:26][CH:27]=2)=[CH:5]1.FC(F)(F)C(OC(=O)C(F)(F)F)=O>O1CCCC1>[NH2:1][C:2]1[N:10]=[C:9]2[CH:8]=[CH:7][C:6]([O:21][C:22]3[CH:23]=[C:24]([NH:28][C:29]([C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[N:32]=4)=[O:30])[CH:25]=[CH:26][CH:27]=3)=[CH:5][N:4]2[CH:3]=1

Participants

4

Reactant 2

HCID 9845Trifluoroacetic anhydrideHCID 68986248N-(3-{[1-(2-amino-2-oxoethyl)-6-{[(4-methylphenyl)sulfonyl]imino}-1,6-dihydropyridin-3-yl]oxy}phenyl)-6-methylpyridine-2-carboxamide

Product 1

HCID 57749229N-{3-[(2-aminoimidazo[1,2-a]pyridin-6-yl)oxy]phenyl}-6-methylpyridine-2-carboxamideYield 22.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of N-(3-{[1-(2-amino-2-oxoethyl)-6-{[(4-methylphenyl)sulfonyl]imino}-1,6-dihydropyridin-3-yl]oxy}phenyl)-6-methylpyridine-2-carboxamide (14.6 g, 27.5 mmol), trifluoroacetic anhydride (31 mL) and tetrahydrofuran (300 mL) was stirred at room temperature for 1 hr. The reaction solution was concentrated under reduced pressure, and ethyl acetate was added to the residue. The mixture was washed with aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, ethanol (200 mL) and 4M aqueous sodium hydroxide solution (80 mL) were added to the residue, and the mixture was stirred at 60° C. for 24 hr. The reaction solution was concentrated under reduced pressure, and ethyl acetate was added to the residue. The mixture was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH silica gel, 0%→100% ethyl acetate-hexane) to give the title compound (2.22 g, 22%) as a pale-brown solid.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure, and ethyl acetate
  2. additionwas added to the residue
  3. washThe mixture was washed with aqueous sodium hydrogen carbonate solution and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltrated
  6. concentrationThe filtrate was concentrated under reduced pressure, ethanol (200 mL) and 4M aqueous sodium hydroxide solution (80 mL)
  7. additionwere added to the residue
  8. stirringthe mixture was stirred at 60° C. for 24 hr
  9. concentrationThe reaction solution was concentrated under reduced pressure, and ethyl acetate
  10. additionwas added to the residue
  11. washThe mixture was washed with water and saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. filtrationfiltrated
  14. concentrationThe filtrate was concentrated under reduced pressure
  15. customthe residue was purified by silica gel column chromatography (NH silica gel, 0%→100% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-97bf83c8f855436184a1e3bc886b7d94
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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