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

HRID 219914

反応式

HRID 219914 の反応式
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]

参加物

8

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-5972301b156a46bc81840e9ccd4519bd
出典データセット
uspto-grants-2012_06
特許番号
US08202865B2

関連ノート

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