2-Methoxyethanol → 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-(2-methoxyethoxy)quinoline-3-carbonitrile

HRID 1837363

反応式

HRID 1837363 の反応式
[Na].[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19](F)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27].[CH3:28][O:29][CH2:30][CH2:31][OH:32]>>[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:4]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:32][CH2:31][CH2:30][O:29][CH3:28])=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][C:14]=1[C:26]#[N:27]

参加物

4

反応物 3

HCID 80192-MethoxyethanolHCID 5360545SodiumHCID 114861534-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile

生成物 1

HCID 53301104-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-(2-methoxyethoxy)quinoline-3-carbonitrile

反応条件

温度
125 °C

実験手順

A mixture of sodium (118 mg, 5.11 mmol) and 2-methoxyethanol (5 mL) is heated at 120-130° C. for 3 hours. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (500 mg, 1.28 mmol) is added and the reaction mixture is heated at 120-125° C. for 1 hour. The temperature of the reaction mixture is increased to 140-150° C. and this temperature is maintained for 2.5 hours. The reaction mixture is cooled to room temperature and diluted with ice cold aqueous sodium bicarbonate. The solid is collected by filtration washing with water and hexane. Purification by flash column chromatography, eluting with 2% methanol in dichloromethane provides 550 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[2-methoxyethoxy]-3-quinolinecarbonitrile, mp 210-212° C.

後処理

  1. temperaturethe reaction mixture is heated at 120-125° C. for 1 hour
  2. temperatureThe temperature of the reaction mixture is increased to 140-150° C.
  3. temperaturethis temperature is maintained for 2.5 hours
  4. temperatureThe reaction mixture is cooled to room temperature
  5. additiondiluted with ice cold aqueous sodium bicarbonate
  6. filtrationThe solid is collected by filtration
  7. washwashing with water and hexane
  8. customPurification by flash column chromatography
  9. washeluting with 2% methanol in dichloromethane

出典と根拠

ORDレコード
ord-af770a3ee36f4aa78aca38859b1212ac
出典データセット
uspto-grants-2004_08
特許番号
US06780996B2

関連ノート

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