Sodium hydride → 7-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-methylthieno[3,2-b]pyridine-6-carbonitrile

HRID 1611509ノート

反応式

HRID 1611509 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[CH:23]=[C:24]([CH3:26])[S: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[CH:23]=[C:24]([CH3:26])[S:25][C:16]=12

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 14766362,4-Dichloro-5-methoxyanilineHCID 222566287-Chloro-2-methylthieno[3,2-b]pyridine-6-carbonitrile

生成物 1

HCID 117262657-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-methylthieno[3,2-b]pyridine-6-carbonitrile収率 22.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A mixture of 2,4-dichloro-5-methoxyaniline (507 mg, 2.64 mmol) and 60% sodium hydride (105.6 mg, 2.64 mmol) in 15 mL of tetrahydrofuran is heated at reflux for 1 hour. The solution is cooled and 7-chloro-2-methylthieno[3,2-b]pyridine-6-carbonitrile (275.3 mg, 1.32 mmol) is added. The reaction mixture is heated at reflux for 6 hours, cooled to room temperature and partitioned between dichloromethane and water. The organic layer is washed with saturated aqueous sodium chloride, dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of 5% ethyl acetate in hexane to 20% ethyl acetate in hexane followed by preparative thin layer chromatography developing with 20% ethyl acetate in dichloromethane, to provide 108 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-methylthieno[3,2-b]pyridine-6-carbonitrile as an off white solid, mp 213-214° C.; 1H NMR (DMSO-d6) δ 2.51 (s, 3H), 3.85 (s, 3H), 7.20 (s, 1H), 7.35 (s, 1H), 7.75 (s, 1H), 8.55 (s, 1H), 9.56 (s, 1H); MS 362.1, 364.3 (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 6 hours
  6. custompartitioned between dichloromethane and water
  7. washThe organic layer is washed with saturated aqueous sodium chloride
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue is purified by flash column chromatography
  12. washeluting with a gradient of 5% ethyl acetate in hexane to 20% ethyl acetate in hexane

出典と根拠

ORDレコード
ord-f40dfa91632c4fd4a784b4c0dcd9e773
出典データセット
uspto-grants-2006_01
特許番号
US06987116B2

反応ノート

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