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Ammonium Chloride → 6-chloro-7-morpholin-4-yl-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

HRID 1098316
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HRID 1098316 반응식
[Cl:1][C:2]1[C:11]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[CH:10][C:5]([C:6]([NH:8][CH3:9])=[O:7])=[C:4]([CH3:18])[CH:3]=1.[F:19][C:20]([F:30])([F:29])[C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1C#N.[Cl-].[NH4+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:10][C:11]=1[N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)[C:6](=[O:7])[NH:8][C:9]([C:22]1[CH:25]=[CH:26][CH:27]=[CH:28][C:21]=1[C:20]([F:30])([F:29])[F:19])=[CH:18]2
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참가 물질

5

반응물 3

HCID 25517Ammonium ChlorideHCID 679722-(Trifluoromethyl)benzonitrileHCID 231568014-chloro-2,N-dimethyl-5-morpholin-4-ylbenzamide

생성물 1

HCID 231567776-chloro-7-morpholin-4-yl-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one수율 13.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

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온도
-78 °C

실험 절차

167 μl of a 1.8 M lithium diisopropylamide THF solution (0.3 mmol) was diluted with 1.5 ml of THF. Thereafter, 1 ml of a THF solution containing 27 mg (0.10 mol) of the 4-chloro-2,N-dimethyl-5-morpholin-4-ylbenzamide prepared in Step B was added dropwise to the diluted solution at −78° C. Thereafter, 1 ml of a THF solution containing 17 mg (0.10 mmol) of 2-(trifluoromethyl)benzonitrile was further added thereto, and the obtained mixture was then stirred at −78° C. for 1 hour. The temperature of the reaction solution was increased to 0° C., and a saturated ammonium chloride aqueous solution was added thereto, followed by extraction with ethyl acetate. The extract was washed with a saturated saline solution, and was then dried over anhydrous sodium sulfate, followed by concentration under reduced pressure. Thereafter, the obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2 to 1:1), so as to obtain 5.4 mg (13%) of 6-chloro-7-morpholin-4-yl-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one in the form of a colorless solid.

후처리

  1. additionwas added dropwise to the diluted solution at −78° C
  2. additionwas further added
  3. temperatureThe temperature of the reaction solution was increased to 0° C.
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe extract was washed with a saturated saline solution
  6. dry with materialwas then dried over anhydrous sodium sulfate
  7. concentrationfollowed by concentration under reduced pressure
  8. customThereafter, the obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2 to 1:1)

출처 및 근거

ORD 기록
ord-8062e71fd28342db8d3e8189a94e17ef
출처 데이터셋
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08143274B2

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