Sodium hydride → 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-iodothieno[2,3-b]pyridine-5-carbonitrile

HRID 1178634

反応式

HRID 1178634 の反応式
[Cl:1][C:2]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:3]=1[NH2:4].[H-].[Na+].Cl[C:15]1[C:20]([C:21]#[N:22])=[CH:19][N:18]=[C:17]2[S:23][C:24]([I:26])=[CH:25][C:16]=12>O1CCCC1>[Cl:1][C:2]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:3]=1[NH:4][C:15]1[C:20]([C:21]#[N:22])=[CH:19][N:18]=[C:17]2[S:23][C:24]([I:26])=[CH:25][C:16]=12

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 14766362,4-Dichloro-5-methoxyanilineHCID 100417134-Chloro-2-iodothieno[2,3-B]pyridine-5-carbonitrile

生成物 1

HCID 102543834-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-iodothieno[2,3-b]pyridine-5-carbonitrile収率 18.8%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A mixture of 2,4-dichloro-5-methoxyaniline (1.1 g, 5.7 mmol) and 60% sodium hydride (285 mg, 9.9 mmol) in 30 mL of tetrahydrofuran is heated at reflux for 1 hour. The solution is cooled and 4-chloro-2-iodothieno[2,3-b]pyridine-5-carbonitrile (1.0 g, 3.12 mmol) is added. The reaction mixture is heated at reflux for 5 hours then allowed to stir at room temperature overnight. The resultant dark solution is partitioned between ethyl acetate and water. The organic layer is washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with 0.5: 9.5 methanol:dichloromethane to provide 0.28 g of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-2-iodothieno[2,3-b]pyridine-5-carbonitrile as an off white solid, mp 231–233° C. An additional 0.09 g is obtained by chromatography of a mixture of unreacted starting material and product using a gradient of 9:1 to 1:1 hexane:ethyl acetate. 1H NMR (DMSO-d6) δ 3.87 (s, 3H), 7.36 (s, 1H), 7.76 (s, 1H), 8.11 (s, 1H), 8.39 (s, 1H), 9.76 (s, 1H); MS 473.8 (M−H)−.

後処理

  1. temperatureis heated
  2. temperatureat reflux for 1 hour
  3. temperatureThe solution is cooled
  4. temperatureThe reaction mixture is heated
  5. temperatureat reflux for 5 hours
  6. customThe resultant dark solution is partitioned between ethyl acetate and water
  7. washThe organic layer is washed with water
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue is purified by flash column chromatography
  12. washeluting with 0.5: 9.5 methanol

出典と根拠

ORDレコード
ord-7ac6c9d74fe246139a1a5e165eeab302
出典データセット
uspto-grants-2007_10
特許番号
US07276519B2

関連ノート

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