1-[2-(2-Hydroxyethoxy)ethyl]piperazine → 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-{2-[2-(1-piperazinyl)-ethoxy]ethoxy)-3-quinolinecarbonitrile

HRID 1837354

反応式

HRID 1837354 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].[N:28]1([CH2:34][CH2:35][O:36][CH2:37][CH2:38][OH:39])[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1>>[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:39][CH2:38][CH2:37][O:36][CH2:35][CH2:34][N:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[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 1394361-[2-(2-Hydroxyethoxy)ethyl]piperazineHCID 5360545SodiumHCID 114861534-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile

生成物 1

HCID 104601024-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-{2-[2-(1-piperazinyl)-ethoxy]ethoxy)-3-quinolinecarbonitrile

反応条件

温度
120 °C

実験手順

A mixture of sodium (50 mg, 2.2 mmol) in 1 mL of 2-[2-(1-piperazinyl)ethoxy]ethanol is heated at 120° C. for 2 hours. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (150 mg, 0.38 mmol) is added and the reaction mixture is heated at 140-145° C. for 2 hours, then cooled to room temperature. The reaction mixture is partitioned between saturated sodium bicarbonate and ethyl acetate. The organic layer is dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of 3% methanol in dichloromethane to 1% ammonium hydroxide and 30% methanol in dichloromethane followed by recrystallization from acetone and hexane to provide 124 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-{2-[2-(1-piperazinyl)-ethoxy]ethoxy)-3-quinolinecarbonitrile, mp 88-90° C.

後処理

  1. temperaturethe reaction mixture is heated at 140-145° C. for 2 hours
  2. temperaturecooled to room temperature
  3. customThe reaction mixture is partitioned between saturated sodium bicarbonate and ethyl acetate
  4. dry with materialThe organic layer is dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by flash column chromatography
  8. washeluting with a gradient of 3% methanol in dichloromethane to 1% ammonium hydroxide and 30% methanol in dichloromethane
  9. customfollowed by recrystallization from acetone and hexane

出典と根拠

ORDレコード
ord-528d8a2078a94c878a1a524dbed2cb81
出典データセット
uspto-grants-2004_08
特許番号
US06780996B2

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