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-thiazole-4-carboxamide

HRID 1874607Notes

Reaction equation

HRID 1874607 reaction equation
[S: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][S: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 3042714-Thiazolecarboxylic acidHCID 516892Sodium BicarbonateHCID 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 57749100N-{6-[5-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)-2-methylphenoxy][1,2,4]triazolo[1,5-a]pyridin-2-yl}-1,3-thiazole-4-carboxamideYield 82%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1,3-thiazole-4-carboxylic acid (121 mg, 938 μmol) in tetrahydrofuran (3 mL) were added oxalyl chloride (102 μL, 1.17 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 (200 mg, 0.469 mmol) were dissolved in pyridine (5 mL), and the mixture was stirred at room temperature for 16 hr. A saturated aqueous sodium hydrogen carbonate solution (15 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20 mL, 5 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→99/1), 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 (206 mg, 82%) as a colorless powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. stirringthe mixture was stirred at room temperature for 16 hr
  3. extractionthe mixture was extracted with ethyl acetate (20 mL, 5 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→99/1), 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-8a113d5448ee4227931414de3dd0be8f
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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