Tetrahydrofuran → [5-(5-Cyanopyridin-3-ylethynyl)-2-fluorophenyl]-carbamic acid methyl ester

HRID 606958

反応式

HRID 606958 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]#[C:10][C:11]2[CH:12]=[N:13][CH:14]=[C:15]([CH:18]=2)[C:16]#[N:17])[CH:5]=[CH:6][C:7]=1[F:8].CN[C:21](Cl)=[O:22].[O:24]1CCC[CH2:25]1>N1C=CC=CC=1.O>[CH3:25][O:24][C:21](=[O:22])[NH:1][C:2]1[CH:3]=[C:4]([C:9]#[C:10][C:11]2[CH:12]=[N:13][CH:14]=[C:15]([C:16]#[N:17])[CH:18]=2)[CH:5]=[CH:6][C:7]=1[F:8]

参加物

6

反応物 3

HCID 8028TetrahydrofuranHCID 80931Methylcarbamoyl chlorideHCID 670478225-(3-Amino-4-fluorophenylethynyl)-nicotinonitrile

生成物 1

HCID 67047862[5-(5-Cyanopyridin-3-ylethynyl)-2-fluorophenyl]-carbamic acid methyl ester収率 5%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 1049Pyridine溶媒

実験手順

Dissolve 5-(3-amino-4-fluorophenylethynyl)-nicotinonitrile, (prepared as described in EXAMPLE 160), (0.4 g, 1.7 mmol) in anhydrous pyridine. Add a solution of methylcarbamyl chloride (0.17 g, 1.8 mmol) in anhydrous tetrahydrofuran carefully to the reaction and stir overnight at room temperature. Concentrate and dissolve the crude reaction in ethyl acetate and water. Wash the organic layer with water, an aqueous saturated solution of sodium chloride, dry (potassium carbonate), filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 10:90 ethyl acetate:dichloromethane, and then further purify on C-18 silica, eluting with 10:90 to 50:50 using an aqueous 0.1% solution of trifluoroacetic acid and a 0.1% solution of trifluoroacetic acid in acetonitrile). Concentrate, partition the residue between ethyl acetate and an aqueous saturated solution of sodium bicarbonate and separate the layers. Wash the organic layer with an aqueous saturated solution of sodium chloride, dry (potassium carbonate), filter and concentrate to give the title compound as a white solid (25 mg, 5%).

後処理

  1. customcarefully to the reaction
  2. concentrationConcentrate
  3. dissolutiondissolve the crude
  4. customreaction in ethyl acetate
  5. washWash the organic layer with water
  6. dry with materialan aqueous saturated solution of sodium chloride, dry (potassium carbonate)
  7. filtrationfilter
  8. concentrationconcentrate
  9. custompurify (silica gel chromatography
  10. washeluting with 0:100 to 10:90 ethyl acetate
  11. customdichloromethane, and then further purify on C-18 silica
  12. washeluting with 10:90 to 50:50 using an aqueous 0.1% solution of trifluoroacetic acid
  13. concentrationConcentrate
  14. custompartition the residue between ethyl acetate
  15. customan aqueous saturated solution of sodium bicarbonate and separate the layers
  16. washWash the organic layer with an aqueous saturated solution of sodium chloride
  17. dry with materialdry (potassium carbonate)
  18. filtrationfilter
  19. concentrationconcentrate

出典と根拠

ORDレコード
ord-0ecb0489d36a4e9e8a046ec05c8f5882
出典データセット
uspto-grants-2011_03
特許番号
US07915424B2

関連ノート

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