4-Fluorophenyl isocyanate → N-(4-(7-(benzyloxy)-6-cyano-4-quinolyl)oxyphenyl)-N'-(4-fluorophenyl)urea

HRID 387721노트

반응식

HRID 387721 반응식
[NH2:1][C:2]1[CH:28]=[CH:27][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[C:14]([C:17]#[N:18])[CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[F:29][C:30]1[CH:35]=[CH:34][C:33]([N:36]=[C:37]=[O:38])=[CH:32][CH:31]=1>C1(C)C=CC=CC=1.C(#N)C>[CH2:20]([O:19][C:13]1[CH:12]=[C:11]2[C:16]([C:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:37]([NH:36][C:33]4[CH:34]=[CH:35][C:30]([F:29])=[CH:31][CH:32]=4)=[O:38])=[CH:28][CH:27]=3)=[CH:8][CH:9]=[N:10]2)=[CH:15][C:14]=1[C:17]#[N:18])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

참가 물질

5

반응물 2

HCID 709554-Fluorophenyl isocyanateHCID 229368314-(4-Aminophenoxy)-7-(benzyloxy)-6-cyanoquinoline

생성물 1

HCID 22936525N-(4-(7-(benzyloxy)-6-cyano-4-quinolyl)oxyphenyl)-N'-(4-fluorophenyl)urea수율 91.9%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 6342Acetonitrile용매

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온도
120 °C

실험 절차

4-(4-Aminophenoxy)-7-(benzyloxy)-6-cyanoquinoline (7.776 g, 21.2 mmol) was dissolved in a toluene (400 ml) and acetonitrile (200 ml) mixed solvent, and then 4-fluorophenyl isocyanate (3.68 ml, 31.7 mmol) was added and the mixture was heated to reflux at 120° C. for 1 hour. The reaction solution was concentrated under reduced pressure, the residue was suspended in tetrahydrofuran (150 ml), and then hexane (150 ml) was added, sonication was performed, and the precipitated crystals were filtered out and dried under reduced pressure to obtain N-(4-(7-(benzyloxy)-6-cyano-4-quinolyl)oxyphenyl)-N′-(4-fluorophenyl)urea (9.81 g, 19.4 mmol, 91.9%) as light brown crystals. These were dissolved in trifluoroacetic acid (100 ml) and thioanisole (9.13 ml, 77.7 mmol) under a nitrogen atmosphere, and the solution was stirred at 60° C. for 12 hours. The reaction solution was concentrated under reduced pressure, and after adding tetrahydrofuran (50 ml) and then 1N aqueous sodium hydroxide (150 ml) and water (150 ml) to the residue, the mixture was stirred and the precipitated crystals were filtered out and washed with water, diethyl ether and ethyl acetate and dried at 70° C. to obtain the title compound (3.646 g, 8.36 mmol, 43.0%) as yellow crystals.

후처리

  1. additionmixed solvent
  2. temperaturethe mixture was heated
  3. concentrationThe reaction solution was concentrated under reduced pressure
  4. additionhexane (150 ml) was added
  5. customsonication
  6. filtrationthe precipitated crystals were filtered out
  7. customdried under reduced pressure

출처 및 근거

ORD 기록
ord-7bf530b465d94ab0abc4866c8e771d3e
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08372981B2

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