Oxalyl chloride → N-{6-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy][1,2,4]triazolo[1,5-a]pyridin-2-yl}-1,3-oxazole-4-carboxamide

HRID 1874597Notes

Reaction equation

HRID 1874597 reaction equation
[O:1]1[CH:5]=[C:4]([C:6]([OH:8])=O)[N:3]=[CH:2]1.C(Cl)(=O)C(Cl)=O.[NH2:15][C:16]1[N:45]=[C:19]2[CH:20]=[CH:21][C:22]([O:24][C:25]3[CH:26]=[C:27]([NH:31][C:32](=[O:44])[C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([C:42]#[N:43])([CH3:41])[CH3:40])[CH:34]=4)[CH:28]=[CH:29][CH:30]=3)=[CH:23][N:18]2[N:17]=1.C(=O)([O-])O.[Na+]>O1CCCC1.N1C=CC=CC=1.CN(C)C=O>[C:42]([C:39]([C:35]1[CH:34]=[C:33]([C:32]([NH:31][C:27]2[CH:26]=[C:25]([CH:30]=[CH:29][CH:28]=2)[O:24][C:22]2[CH:21]=[CH:20][C:19]3[N:18]([N:17]=[C:16]([NH:15][C:6]([C:4]4[N:3]=[CH:2][O:1][CH:5]=4)=[O:8])[N:45]=3)[CH:23]=2)=[O:44])[CH:38]=[CH:37][CH:36]=1)([CH3:41])[CH3:40])#[N:43]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 142814301,3-Oxazole-4-carboxylic acidHCID 68990682N-{3-[(2-amino[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 57749182N-{6-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy][1,2,4]triazolo[1,5-a]pyridin-2-yl}-1,3-oxazole-4-carboxamideYield 81%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1,3-oxazole-4-carboxylic acid (145 mg, 1.29 mmol) in tetrahydrofuran (3 mL) were added oxalyl chloride (157 μL, 1.80 mmol) and N,N-dimethylformamide (20 μL), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure. The obtained residue and the above-mentioned N-{3-[(2-amino[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide (213 mg, 516 μmol) were dissolved in pyridine (8 mL), and the mixture was stirred at room temperature for 25 hr. A saturated aqueous sodium hydrogen carbonate solution (10 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20 mL, 2×10 mL). The combined organic layer was washed with saturated brine (5 mL) and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/methanol=100/0→97/3), and fractions containing the desired product were concentrated under reduced pressure. Diisopropyl ether was added to the obtained residue. The obtained precipitate was collected by filtration and dried to give the title compound (211 mg, 81%) as a colorless powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. stirringthe mixture was stirred at room temperature for 25 hr
  3. extractionthe mixture was extracted with ethyl acetate (20 mL, 2×10 mL)
  4. washThe combined organic layer was washed with saturated brine (5 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationThe insoluble material was filtered off
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/methanol=100/0→97/3), and fractions
  9. additioncontaining the desired product
  10. concentrationwere concentrated under reduced pressure
  11. additionDiisopropyl ether was added to the obtained residue
  12. filtrationThe obtained precipitate was collected by filtration
  13. customdried

Sources & evidence

ORD record
ord-62a6c51a1d7f403899c0e7a6adb57761
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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