N-bromobutanimide → N-{2-Chloro-3-[5-(2-chloro-4-pyrimidinyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]phenyl}-2,6-difluorobenzenesulfonamide

HRID 590077

反応式

HRID 590077 の反応式
C1C(=O)N(Br)C(=O)C1.[Cl:9][C:10]1[C:15](/[C:16](/O)=[CH:17]\[C:18]2[CH:23]=[CH:22][N:21]=[C:20]([Cl:24])[N:19]=2)=[CH:14][CH:13]=[CH:12][C:11]=1[NH:26][S:27]([C:30]1[C:35]([F:36])=[CH:34][CH:33]=[CH:32][C:31]=1[F:37])(=[O:29])=[O:28].[O:38]1[CH2:43][CH2:42][CH:41]([C:44](=[S:46])[NH2:45])[CH2:40][CH2:39]1>CC(N(C)C)=O.O>[Cl:9][C:10]1[C:15]([C:16]2[N:45]=[C:44]([CH:41]3[CH2:42][CH2:43][O:38][CH2:39][CH2:40]3)[S:46][C:17]=2[C:18]2[CH:23]=[CH:22][N:21]=[C:20]([Cl:24])[N:19]=2)=[CH:14][CH:13]=[CH:12][C:11]=1[NH:26][S:27]([C:30]1[C:35]([F:36])=[CH:34][CH:33]=[CH:32][C:31]=1[F:37])(=[O:29])=[O:28]

参加物

6

反応物 3

HCID 67184N-bromobutanimideHCID 13197204Oxane-4-carbothioamideHCID 136342910N-{2-chloro-3-[(E)-2-(2-chloro-4-pyrimidinyl)-1-hydroxyethenyl]phenyl}-2,6-difluorobenzenesulfonamide

生成物 1

HCID 57989796N-{2-Chloro-3-[5-(2-chloro-4-pyrimidinyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]phenyl}-2,6-difluorobenzenesulfonamide収率 50.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 31374Dimethylacetamide溶媒

実験手順

Recrystallized NBS (1.56 g, 8.8 mmol) was added to a suspension of N-{2-chloro-3-[(E)-2-(2-chloro-4-pyrimidinyl)-1-hydroxyethenyl]phenyl}-2,6-difluorobenzenesulfonamide (4.02 g, 8.80 mmol) in DMA (15 mL) in an ice-bath. The reaction was immediately removed from the ice bath and allowed to warm to rt over 0.5 h. Tetrahydro-2H-pyran-4-carbothioamide (1.27 g, 8.80 mmol) was added and the reaction warmed in an oil bath (rt to 65° C.). The reaction was diluted with water (100 mL) which caused the precipitation of a yellow solid. The solid was then dissolved by the addition of EtOAc (100 mL) and the phases separated. The aqueous phase was extracted with EtOAc (50 mL). The combined organic phase was filtered through Whatman 1 PS (phase separating) paper and concentrated under vacuum to a crude orange residue. The residue was purified by silica gel chromatography eluting with 0-100% EtOAc/hexanes to give the title compound of Step A as a bright yellow solid (2.56 g; 50.1% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.88 (s, 1H), 8.55 (d, J=5.4 Hz, 1H), 7.62-7.74 (m, 1H), 7.48-7.57 (m, 2H), 7.42-7.47 (m, 1H), 7.22 (t, J=9.1 Hz, 2H), 6.54 (d, J=5.3 Hz, 1H), 3.92 (d, J=11.0 Hz, 2H), 3.41-3.51 (m, 2H), 2.03 (br. s., 2H), 1.69-1.83 (m, J=12.1, 12.1, 11.9, 4.2 Hz, 2H).

後処理

  1. customThe reaction was immediately removed from the ice bath
  2. temperaturethe reaction warmed in an oil bath (rt to 65° C.)
  3. customthe precipitation of a yellow solid
  4. dissolutionThe solid was then dissolved by the addition of EtOAc (100 mL)
  5. customthe phases separated
  6. extractionThe aqueous phase was extracted with EtOAc (50 mL)
  7. filtrationThe combined organic phase was filtered through Whatman 1 PS (phase separating) paper
  8. concentrationconcentrated under vacuum to a crude orange residue
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with 0-100% EtOAc/hexanes

出典と根拠

ORDレコード
ord-c4a58ba65f3b485bb82011a3a2fdc8f5
出典データセット
uspto-grants-2016_01
特許番号
US09233956B2

関連ノート

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