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Methanesulfonamide → 4-[(5-Chloro-6-fluoropyridin-3-yl)oxy]-2,5-difluoro-N-(methylsulfonyl)benzamide

HRID 2048055
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HRID 2048055 반응식
[CH3:1][S:2]([NH2:5])(=[O:4])=[O:3].C1CCN2C(=NCCC2)CC1.[Cl:17][C:18]1[CH:19]=[C:20]([O:25][C:26]2[C:41]([F:42])=[CH:40][C:29]([C:30](OC3C=CC(C)=CC=3)=[O:31])=[C:28]([F:43])[CH:27]=2)[CH:21]=[N:22][C:23]=1[F:24]>CC#N.CCOC(C)=O>[Cl:17][C:18]1[CH:19]=[C:20]([O:25][C:26]2[C:41]([F:42])=[CH:40][C:29]([C:30]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])=[O:31])=[C:28]([F:43])[CH:27]=2)[CH:21]=[N:22][C:23]=1[F:24]
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참가 물질

6

반응물 3

HCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 58042398p-Tolyl 4-(5-chloro-6-fluoropyridin-3-yloxy)-2,5-difluorobenzoate

생성물 1

HCID 580423644-[(5-Chloro-6-fluoropyridin-3-yl)oxy]-2,5-difluoro-N-(methylsulfonyl)benzamide수율 36.1%

시약·촉매·용매 2

HCID 6342Acetonitrile용매
HCID 8857
Ethyl Acetate
용매

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온도
45 °C

실험 절차

Methanesulfonamide (52.0 mg, 0.547 mmol) was suspended in MeCN (3 mL) in a sealed vial. 2,3,4,6,7,8,9,10-Octahydropyrimidol[1,2-a]azepine (0.085 mL, 0.57 mmol) was added followed by 4-methylphenyl 4-[(5-chloro-6-fluoropyridin-3-yl)oxy]-2,5-difluorobenzoate (Preparation 67, 215.0 mg, 0.546 mmol). The mixture was heated at 45° C. for 2 hours. The reaction mixture was diluted in EtOAc (15 mL), then washed with 10% aqueous citric acid solution (2×15 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting solid was partitioned between DCM (10 mL) and water (10 mL). The organic layer was further washed water (2×10 mL) and concentrated in vacuo to yield the title compound as a white solid (75 mg). EtOAc (15 mL) was added to the combined aqueous. The organic layer was then washed with water (3×10 mL), dried over sodium sulfate, filtered and concentrated in vacuo to yield a second batch of the title compound as a white solid (75.0 mg, 35%):

후처리

  1. washwashed with 10% aqueous citric acid solution (2×15 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe resulting solid was partitioned between DCM (10 mL) and water (10 mL)
  6. washThe organic layer was further washed water (2×10 mL)
  7. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-8998601744e04895b9f43ef675d76ee3
출처 데이터셋
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08592629B2

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