Pyridine → N-[4-(3-benzyl-[1,2,4]oxadiazol-5-yl)-pyridin-2-yl]-benzamide

HRID 714350

Reaction equation

HRID 714350 reaction equation
[C:1]([NH:9][C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][N:18]=1)[C:13]([OH:15])=O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.O[N:26]=[C:27]([NH2:35])[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.N1C=CC=CC=1.[OH-].COC(NS([N+](CC)(CC)CC)(=O)=O)=O>ClCCl.CN(C)C=O.C(OCC)(=O)C>[CH2:28]([C:27]1[N:35]=[C:13]([C:12]2[CH:16]=[CH:17][N:18]=[C:10]([NH:9][C:1](=[O:8])[C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:11]=2)[O:15][N:26]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

9

Reactant 5

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 2731007N'-hydroxy-2-phenylethanimidamideHCID 11032497(Methoxycarbonylsulfamoyl)triethylammonium hydroxideHCID 64393851HCID 64393851, compound

Product 1

HCID 67153834N-[4-(3-benzyl-[1,2,4]oxadiazol-5-yl)-pyridin-2-yl]-benzamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-benzamidoisonicotinic acid (0.35 g, 1.44 mmol) and N,N-dimethylformamide (0.1 mL) in dichloromethane (5 mL) was added oxalyl chloride (0.15 mL, 1.73 mmol) at ambient temperature. The resulting mixture was stirred at ambient temperature for 1 hour and concentrated in vacuo to dryness. The residue was dissolved in N,N-dimethylformamide (2 mL) and added to a solution of N′-hydroxy-2-phenylacetimidamide (0.24 g, 1.59 mmol) and pyridine (0.3 mL, 3.70 mmol) in N,N-dimethylformamide (1 mL) at 0° C. The reaction mixture was stirred at ambient temperature for 3 hours, diluted with ethyl acetate (40 mL), washed with water (20 mL) and brine (20 mL). The organic solution was dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The residue was dissolved in toluene (10 mL), followed by the addition of (methoxycarbonylsulfamoyl)triethylammonium hydroxide (0.53 g, 2.16 mmol). The mixture was refluxed for 1 hour and concentrated in vacuo. The residue was purified by column chromatography to give N-[4-(3-benzyl-[1,2,4]oxadiazol-5-yl)-pyridin-2-yl]-benzamide as a colorless solid (0.06 g 12%): mp 150-151° C.; 1H NMR (300 MHz, CDCl3) δ 9.06 (s, 1H), 8.69 (s, 1H), 8.46 (d, J=4.9 Hz, 1H), 7.94-7.91 (m, 2H), 7.72-7.69 (m, 1H), 7.62-7.48 (m, 3H), 7.39-7.24 (m, 5H), 4.16 (s, 2H); MS (ES+) m/z 357.5 (M+1).

Workup

  1. concentrationconcentrated in vacuo to dryness
  2. dissolutionThe residue was dissolved in N,N-dimethylformamide (2 mL)
  3. stirringThe reaction mixture was stirred at ambient temperature for 3 hours
  4. washwashed with water (20 mL) and brine (20 mL)
  5. dry with materialThe organic solution was dried over anhydrous sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in toluene (10 mL)
  9. temperatureThe mixture was refluxed for 1 hour
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-a056803727484e82aaaf77c0a5bf2208
Source dataset
uspto-grants-2015_11
Patent number
US09187426B2

Linked notes

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