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

HRID 219914

반응식

HRID 219914 반응식
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]

참가 물질

8

반응물 5

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

생성물 1

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

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-5972301b156a46bc81840e9ccd4519bd
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202865B2

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