Ethanol → N-{3-[(2-amino[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy]-4-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide

HRID 1874605Notes

Reaction equation

HRID 1874605 reaction equation
[C:1]([C:3]([C:6]1[CH:7]=[C:8]([C:12]([NH:14][C:15]2[CH:16]=[CH:17][C:18]([CH3:37])=[C:19]([CH:36]=2)[O:20][C:21]2[CH:22]=[CH:23][C:24]([NH:27][C:28]([NH:30]C(=O)OCC)=S)=[N:25][CH:26]=2)=[O:13])[CH:9]=[CH:10][CH:11]=1)([CH3:5])[CH3:4])#[N:2].C(O)C.Cl.NO.C([N:47](CC)C(C)C)(C)C>CO>[NH2:47][C:28]1[N:27]=[C:24]2[CH:23]=[CH:22][C:21]([O:20][C:19]3[CH:36]=[C:15]([NH:14][C:12](=[O:13])[C:8]4[CH:9]=[CH:10][CH:11]=[C:6]([C:3]([C:1]#[N:2])([CH3:5])[CH3:4])[CH:7]=4)[CH:16]=[CH:17][C:18]=3[CH3:37])=[CH:26][N:25]2[N:30]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 81531DiisopropylethylamineHCID 443297Hydroxyamine hydrochlorideHCID 86631986Ethyl ({5-[5-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)-2-methylphenoxy]pyridin-2-yl}carbamothioyl)carbamate

Product 1

HCID 68985382N-{3-[(2-amino[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy]-4-methylphenyl}-3-(1-cyano-1-methylethyl)benzamideYield 35%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of the above-mentioned crude product, ethyl ({5-[5-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)-2-methylphenoxy]pyridin-2-yl}carbamothioyl)carbamate, in methanol (100 mL)/ethanol (100 mL) were added hydroxylamine hydrochloride (5.08 g, 73.1 mmol) and N,N-diisopropylethylamine (15.3 mL, 87.8 mmol), and the mixture was stirred with heating at 60° C. for 15 hr. The reaction mixture was concentrated under reduced pressure, water (100 mL) was added to the residue, and the mixture was extracted with ethyl acetate (200 mL, 50 mL). The combined organic layer was washed with saturated brine (20 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, hexane/ethyl acetate=30/70→0/100), and fractions containing the desired product were concentrated under reduced pressure to give the title compound (1.81 g, 35%) as a colorless solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, water (100 mL)
  2. additionwas added to the residue
  3. extractionthe mixture was extracted with ethyl acetate (200 mL, 50 mL)
  4. washThe combined organic layer was washed with saturated brine (20 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, hexane/ethyl acetate=30/70→0/100), and fractions
  9. additioncontaining the desired product
  10. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-55e1b260f6d347c4afc2f6212086cbe3
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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