Methanol → 6-Bromo-4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-methoxy-3-quinolinecarbonitrile

HRID 1593780

반응식

HRID 1593780 반응식
[Br:1][C:2]1[CH:25]=[CH:24][C:5]([NH:6][CH:7]=[C:8]([C:22]#[N:23])[C:9]([NH:11][C:12]2[CH:17]=[C:16]([O:18][CH3:19])[C:15]([Cl:20])=[CH:14][C:13]=2[Cl:21])=O)=[CH:4][C:3]=1[O:26][CH3:27].CO.P(Cl)(Cl)(Cl)=O>C(#N)C>[Br:1][C:2]1[CH:25]=[C:24]2[C:5](=[CH:4][C:3]=1[O:26][CH3:27])[N:6]=[CH:7][C:8]([C:22]#[N:23])=[C:9]2[NH:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[C:15]([Cl:20])=[CH:14][C:13]=1[Cl:21]

참가 물질

5

반응물 3

HCID 887Methanol2회HCID 24813Phosphorus oxychloride2회HCID 693122584-bromo-3-methoxyanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide

생성물 1

HCID 117121406-Bromo-4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-methoxy-3-quinolinecarbonitrile수율 39%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
2.5 °C

실험 절차

To a suspension of (5.13 g, 11 mmol) of 4-bromo-3-methoxyanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide in 400 mL of acetonitrile was added 1.5 mL of methanol. The mixture was heated to reflux and phosphorous oxychloride (4.10 mL, 44.0 mmol) was added dropwise. The resulting mixture was heated at reflux for 26 hours. Additional phosphorous oxychloride (2.1 mL) and methanol (0.75 mL) were added and the mixture was heated at reflux for 21 hours. After cooling to 0-5° C. in an ice-bath, the solid was collected by filtration, washed with cold acetonitrile (100 mL) and then suspended in tetrahydrofuran (100 mL). To the tetrahydrofuran suspension was added concentrated ammonium hydroxide and the mixtures were stirred for 1 hour. Water (300 mL) was added and stirring was continued for 1 hour. The solid was collected by filtration, washed with hot water (46° C.), acetonitrile and dried in vacuo overnight to recover 2.1 g of 4-bromo-3-methoxyanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide. The acetonitrile filtrate and washing were combined and concentrated aqueous ammonium hydroxide was added. The resulting acetonitrile mixture was stirred for 1 hour. Water was added and stirring was continued for 1 hour. The solid was collected by filtration, washed with water, ethyl acetate and ether, then dried in vacuo to provide 1.92 g (39%) of 6-bromo-4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-methoxy-3-quinolinecarbonitrile as a yellow solid, mp 256-257° C.; 1H NMR (400 MHz, DMSO-d6) δ 3.85 (s, 3H), 4.04 (s, 3H), 7.37 (s, 1H), 7.46 (s, 1H), 7.75 (s, 1H), 8.56(s, 1H), 8.89 (s, 1H), 9.93 (s, 1H); MS (ES) m/z451.9, 454.0 (M+H)+

후처리

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. temperatureThe resulting mixture was heated
  4. temperatureat reflux for 26 hours
  5. temperaturethe mixture was heated
  6. temperatureat reflux for 21 hours
  7. filtrationthe solid was collected by filtration
  8. washwashed with cold acetonitrile (100 mL)
  9. additionTo the tetrahydrofuran suspension was added concentrated ammonium hydroxide
  10. additionWater (300 mL) was added
  11. stirringstirring
  12. waitwas continued for 1 hour
  13. filtrationThe solid was collected by filtration
  14. washwashed with hot water (46° C.), acetonitrile
  15. customdried in vacuo overnight
  16. customto recover 2.1 g of 4-bromo-3-methoxyanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide
  17. washThe acetonitrile filtrate and washing
  18. additionconcentrated aqueous ammonium hydroxide was added
  19. stirringThe resulting acetonitrile mixture was stirred for 1 hour
  20. additionWater was added
  21. stirringstirring
  22. waitwas continued for 1 hour
  23. filtrationThe solid was collected by filtration
  24. washwashed with water, ethyl acetate and ether
  25. customdried in vacuo

출처 및 근거

ORD 기록
ord-2059bb4d4cef402886d13161534f2743
출처 데이터셋
uspto-grants-2007_11
특허 번호
US07297795B2

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