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N-bromobutanimide → N-{2-Chloro-3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]phenyl}-2,5-difluorobenzenesulfonamide

HRID 590084
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HRID 590084 반응식
[Cl:1][C:2]1[C:7](/[C:8](/O)=[CH:9]\[C:10]2[CH:15]=[CH:14][N:13]=[C:12]([Cl:16])[N:11]=2)=[CH:6][CH:5]=[CH:4][C:3]=1[NH:18][S:19]([C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[F:29])(=[O:21])=[O:20].C1C(=O)N(Br)C(=O)C1.[CH3:38][C:39]([CH3:44])([CH3:43])[C:40](=[S:42])[NH2:41]>CC(N(C)C)=O.CCOC(C)=O>[Cl:1][C:2]1[C:7]([C:8]2[N:41]=[C:40]([C:39]([CH3:44])([CH3:43])[CH3:38])[S:42][C:9]=2[C:10]2[CH:15]=[CH:14][N:13]=[C:12]([Cl:16])[N:11]=2)=[CH:6][CH:5]=[CH:4][C:3]=1[NH:18][S:19]([C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[F:29])(=[O:21])=[O:20]
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참가 물질

6

반응물 3

HCID 67184N-bromobutanimideHCID 30311302,2-DimethylpropanethioamideHCID 136342907N-{2-Chloro-3-[(E)-2-(2-chloro-4-pyrimidinyl)-1-hydroxyethenyl]phenyl}-2,5-difluorobenzenesulfonamide

생성물 1

HCID 57989680N-{2-Chloro-3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]phenyl}-2,5-difluorobenzenesulfonamide수율 36%

시약·촉매·용매 2

HCID 8857
Ethyl Acetate
용매
HCID 31374Dimethylacetamide용매

실험 절차

To a solution of N-{2-chloro-3-[(E)-2-(2-chloro-4-pyrimidinyl)-1-hydroxyethenyl]phenyl}-2,5-difluorobenzenesulfonamide (3.0 g, 6.55 mmol) in DMA (25 mL) was added NBS (1.165 g, 6.55 mmol). After stirring for 1 h at rt, 2,2-dimethylpropanethioamide (0.767 g, 6.55 mmol) was added and the reaction mixture was stirred at 80° C. for 2 h. The reaction mixture was diluted with EtOAc (100 mL) and extracted five times with water. The organic layer was dried over anhydrous NaSO4, adsorbed onto silica gel, and purified via column chromatography, eluting with 0-50% EtOAc/DCM. The desired fractions were combined and concentrated to generate 1.31 g (2.36 mmol, 36.0% yield) of the title compound as a yellow powder. 1H NMR (400 MHz, DMSO-d6): δ 10.74 (s, 1H), 8.56 (d, J=5.4 Hz, 1H), 7.41-7.58 (m, 6H), 6.57 (d, J=5.4 Hz, 1H), 1.42 (s, 9H). MS (ESI): 555.0 [M+H]+.

후처리

  1. stirringthe reaction mixture was stirred at 80° C. for 2 h
  2. extractionextracted five times with water
  3. dry with materialThe organic layer was dried over anhydrous NaSO4
  4. custompurified via column chromatography
  5. washeluting with 0-50% EtOAc/DCM
  6. concentrationconcentrated

출처 및 근거

ORD 기록
ord-96cf1dd261c5486ba435f44004d2564e
출처 데이터셋
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09233956B2

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