Sodium hydride → 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-(pyridin-4-yloxy)-3-quinolinecarbonitrile

HRID 1837362노트

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HRID 1837362 반응식
[H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][N:7]=[CH:6][CH:5]=1.[Cl:10][C:11]1[CH:16]=[C:15]([Cl:17])[C:14]([O:18][CH3:19])=[CH:13][C:12]=1[NH:20][C:21]1[C:30]2[C:25](=[CH:26][C:27](F)=[C:28]([O:31][CH3:32])[CH:29]=2)[N:24]=[CH:23][C:22]=1[C:34]#[N:35]>CN(C=O)C>[Cl:10][C:11]1[CH:16]=[C:15]([Cl:17])[C:14]([O:18][CH3:19])=[CH:13][C:12]=1[NH:20][C:21]1[C:30]2[C:25](=[CH:26][C:27]([O:3][C:4]3[CH:9]=[CH:8][N:7]=[CH:6][CH:5]=3)=[C:28]([O:31][CH3:32])[CH:29]=2)[N:24]=[CH:23][C:22]=1[C:34]#[N:35]

참가 물질

5

반응물 3

HCID 24758Sodium hydride2회HCID 114861534-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrileHCID 178418642HCID 178418642, 화합물

생성물 1

HCID 234980894-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-(pyridin-4-yloxy)-3-quinolinecarbonitrile수율 54.5%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
100 °C

실험 절차

A mixture of sodium hydride (128 mg, 3.2 mmol) and 4-hydroxypyridine (750 mg, 7.89 mmol) in 5 mL of N, N′-dimethylformamide is heated at 100° C. for 1 hour. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (200 mg, 0.51 mmol) is added and the reaction mixture is heated at 130° C. for 2 hours. An additional 21 mg of sodium hydride is added and the reaction mixture is heated at 130° C. for an additional 30 minutes. The reaction mixture is partitioned between ethyl acetate and water. The organic layer is dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by heating with methanol and dichloromethane to provide 130 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-(pyridin-4-yloxy)-3-quinolinecarbonitrile, mp 267-269° C.

후처리

  1. temperaturethe reaction mixture is heated at 130° C. for 2 hours
  2. temperaturethe reaction mixture is heated at 130° C. for an additional 30 minutes
  3. customThe reaction mixture is partitioned between ethyl acetate and water
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified
  8. temperatureby heating with methanol and dichloromethane

출처 및 근거

ORD 기록
ord-f902decce26446459da72492d0992e13
출처 데이터셋
uspto-grants-2004_08
특허 번호
US06780996B2

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