Dimethylformamide → Methyl 4-[5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorobenzoate

HRID 219914Notes

Reaction equation

HRID 219914 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[C:9]([Cl:17])=[N:10][CH:11]=[C:12]([CH:16]=1)[C:13]([OH:15])=O.CN(C=O)C.[NH2:23][C:24](=[N:36]O)[C:25]1[CH:34]=[CH:33][C:28]([C:29]([O:31][CH3:32])=[O:30])=[C:27]([F:35])[CH:26]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.C1COCC1>[Cl:7][C:8]1[CH:16]=[C:12]([C:13]2[O:15][N:36]=[C:24]([C:25]3[CH:34]=[CH:33][C:28]([C:29]([O:31][CH3:32])=[O:30])=[C:27]([F:35])[CH:26]=3)[N:23]=2)[CH:11]=[N:10][C:9]=1[Cl:17]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 2479875,6-Dichloronicotinic acidHCID 76644654Methyl 4-[amino(hydroxyimino)methyl]-2-fluorobenzoate

Product 1

HCID 86645653Methyl 4-[5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorobenzoate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Oxalyl chloride (507.70 μL; 6 mmol) was added to suspension of 5,6-dichloronicotinic acid (FLUKA; 36000-10G; 384 mg; 2 mmol) and DMF (15.40 μL; 0.20 mmol) in DCM (30 mL) and the resulting mixture was stirred at RT for 1 hour. The solution was then evaporated to dryness. The residue was dissolved in THF (5 mL) and added dropwise to a mixture of Intermediate 1 (424.36 mg; 2 mmol), DIEA (1.03 mL; 6 mmol) in THF (5 mL). The reaction mixture was heated in the microwave at 150° C. for 30 min. When cool to RT the solid was filtered, rinsed with ACN, dissolved in DCM and washed with water. The organic layer was then dried over magnesium sulfate, filtered and concentrated to afford the title compound as a slightly yellow solid. 1H NMR (DMSO-d6, 300 MHz) δ 9.18-9.17 (m, 1H), 8.90-8.89 (m, 1H), 8.17-8 (m, 3H), 3.91 (s, 3H). 19F NMR (DMSO-d6, 300 MHz) δ-108.7 ppm. HPLC (Method A) Rt 5.19 min (Purity: 98.0%).

Workup

  1. customThe solution was then evaporated to dryness
  2. dissolutionThe residue was dissolved in THF (5 mL)
  3. temperatureThe reaction mixture was heated in the microwave at 150° C. for 30 min
  4. temperatureWhen cool to RT the solid
  5. filtrationwas filtered
  6. washrinsed with ACN
  7. dissolutiondissolved in DCM
  8. washwashed with water
  9. dry with materialThe organic layer was then dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-5972301b156a46bc81840e9ccd4519bd
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

Loading…