Phosphorus oxychloride → 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-ethoxy-7-fluoro-3-quinolinecarbonitrile

HRID 1593775노트

반응식

HRID 1593775 반응식
[CH2:1]([O:3][C:4]1[CH:27]=[CH:26][C:7]([NH:8][CH:9]=[C:10]([C:24]#[N:25])[C:11]([NH:13][C:14]2[CH:19]=[C:18]([O:20][CH3:21])[C:17]([Cl:22])=[CH:16][C:15]=2[Cl:23])=O)=[CH:6][C:5]=1[F:28])[CH3:2].P(Cl)(Cl)(Cl)=O>C(#N)C.CO>[Cl:23][C:15]1[CH:16]=[C:17]([Cl:22])[C:18]([O:20][CH3:21])=[CH:19][C:14]=1[NH:13][C:11]1[C:26]2[C:7](=[CH:6][C:5]([F:28])=[C:4]([O:3][CH2:1][CH3:2])[CH:27]=2)[N:8]=[CH:9][C:10]=1[C:24]#[N:25]

참가 물질

5

반응물 2

HCID 24813Phosphorus oxychlorideHCID 693122634-ethoxy-3-fluoroanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide

생성물 1

HCID 115459364-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-ethoxy-7-fluoro-3-quinolinecarbonitrile수율 37%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6342Acetonitrile용매

실험 절차

A suspension of 4-ethoxy-3-fluoroanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide (6.28 9, 14.8 mmol) in 54 mL of acetonitrile and 2.0 mL of methanol was heated to reflux and phosphorous oxychloride (8.3 mL, 88.8 mmol) was added dropwise. The mixture was heated at reflux for 17 hours. The resultant solution was concentrated in vacuo and acetonitrile was added to the residue. The solid was collected by filtration, washed with acetonitrile. The solid was suspended in tetrahydrofuran and neutralized with concentrated ammonium hydroxide. After stirring for 30 minutes, water was added and the mixture was stirred for 1 hour. The solid was collected by filtration, washed with water, followed by 1:1 diethyl ether and hexane. The light yellow solid was dried in vacuo to provide 2.2 g (37%) of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-ethoxy-7-fluoro-3-quinolinecarbonitrile, mp 185-187° C.; 1H NMR (400 MHz, DMSO-d6) δ 1.95 (t, J=7 Hz, 3H), 3.87 (s, 3H), 4.29 (q, J=7 Hz, 2H), 7.39 (s, 1H), 7.66-7.81 (m, 2H), 8.09 (d, J=9 Hz, 1H), 8.49 (s, 1H), 9.80 (s, 1H); MS (ES) m/z 406.1, 408.2 (M+H)+

후처리

  1. temperaturewas heated
  2. temperatureto reflux
  3. temperatureThe mixture was heated
  4. temperatureat reflux for 17 hours
  5. concentrationThe resultant solution was concentrated in vacuo and acetonitrile
  6. additionwas added to the residue
  7. filtrationThe solid was collected by filtration
  8. washwashed with acetonitrile
  9. additionwater was added
  10. stirringthe mixture was stirred for 1 hour
  11. filtrationThe solid was collected by filtration
  12. washwashed with water
  13. customThe light yellow solid was dried in vacuo

출처 및 근거

ORD 기록
ord-14fd4a9aa65a4d5ba35d1e375a30f6ef
출처 데이터셋
uspto-grants-2007_11
특허 번호
US07297795B2

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