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

HRID 1874606Notes

Reaction equation

HRID 1874606 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:46]=[C:19]2[CH:20]=[CH:21][C:22]([O:24][C:25]3[CH:26]=[C:27]([NH:32][C:33](=[O:45])[C:34]4[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([C:43]#[N:44])([CH3:42])[CH3:41])[CH:35]=4)[CH:28]=[CH:29][C:30]=3[CH3:31])=[CH:23][N:18]2[N:17]=1.C(=O)([O-])O.[Na+]>O1CCCC1.N1C=CC=CC=1.CN(C)C=O>[C:43]([C:40]([C:36]1[CH:35]=[C:34]([C:33]([NH:32][C:27]2[CH:28]=[CH:29][C:30]([CH3:31])=[C:25]([CH:26]=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:46]=3)[CH:23]=2)=[O:45])[CH:39]=[CH:38][CH:37]=1)([CH3:42])[CH3:41])#[N:44]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 142814301,3-Oxazole-4-carboxylic acidHCID 68985382N-{3-[(2-amino[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy]-4-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 57749336N-{6-[5-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)-2-methylphenoxy][1,2,4]triazolo[1,5-a]pyridin-2-yl}-1,3-oxazole-4-carboxamideYield 79.5%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1,3-oxazole-4-carboxylic acid (107 mg, 946 μmol) in tetrahydrofuran (3 mL) were added oxalyl chloride (123 μL, 1.42 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 N-{3-[(2-amino[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy]-4-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide (202 mg, 473 μmol) were dissolved in pyridine (5 mL), and the mixture was stirred at room temperature for 15 hr. A saturated aqueous sodium hydrogen carbonate solution (10 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (30 mL, 2×10 mL). The combined organic layer was washed with saturated brine (10 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 basic silica gel column chromatography (NH silica gel, ethyl acetate/methanol=100/0→98/2), and fractions containing the desired product were concentrated under reduced pressure. The obtained residue was recrystallized from ethanol to give the title compound (196 mg, 79%) as a colorless powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. stirringthe mixture was stirred at room temperature for 15 hr
  3. extractionthe mixture was extracted with ethyl acetate (30 mL, 2×10 mL)
  4. washThe combined organic layer was washed with saturated brine (10 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 basic silica gel column chromatography (NH silica gel, ethyl acetate/methanol=100/0→98/2), and fractions
  9. additioncontaining the desired product
  10. concentrationwere concentrated under reduced pressure
  11. customThe obtained residue was recrystallized from ethanol

Sources & evidence

ORD record
ord-87c36c12832a47be98871427f4b80ca7
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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