Dimethylformamide → N-{3-[5-(2-Chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide

HRID 590029Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 590029
[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[C:12]([F:29])=[C:13]([NH:17][S:18]([C:21]3[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=3[F:28])(=[O:20])=[O:19])[CH:14]=[CH:15][CH:16]=2)=O)[CH:5]=[CH:4][N:3]=1.CN(C=O)C.C1C(=O)N(Br)C(=O)C1.[CH3:43][CH:44]([CH3:48])[C:45](=[S:47])[NH2:46]>CCOC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:47][C:45]([CH:44]([CH3:48])[CH3:43])=[N:46][C:9]=2[C:11]2[C:12]([F:29])=[C:13]([NH:17][S:18]([C:21]3[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=3[F:28])(=[O:20])=[O:19])[CH:14]=[CH:15][CH:16]=2)[CH:5]=[CH:4][N:3]=1

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 67184N-bromobutanimideHCID 109095072-MethylpropanethioamideHCID 57989720N-(3-(2-(2-chloropyriMidin-4-yl)acetyl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide

Produkt 1

HCID 57989924N-{3-[5-(2-Chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamideAusbeute 45,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

In a 250 mL flask was placed N-{3-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (4 g, 9.05 mmol) and DMF (60 mL) was added. NBS (1.62 g, 9.10 mmol) was added and, after stirring at rt for 40 min, 2-methylpropanethioamide (1.4 g, 13.6 mmol), prepared by a procedure analogous to Intermediate 1, was added. After 4 h at rt, the reaction mixture was poured into 800 mL of EtOAc and washed 4 times with 250 mL of H2O, washed once with 200 mL of brine, and dried over NaSO4. Silica gel was added and the volatiles were removed under reduced pressure. Column chromatography with 10% to 60% EtOAc:Hexane gave 2.15 g (45%) of the title compound. 1H-NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 9.06 (d, J=5.3 Hz, 1H), 8.12-8.30 (m, 1H), 7.93-8.06 (m, 2H), 7.84 (t, J=7.9 Hz, 1H), 7.75 (t, J=9.2 Hz, 2H), 7.37 (d, J=5.3 Hz, 1H), 3.77-3.93 (m, 1H), and 1.89 (d, J=6.8 Hz, 6H). MS (ESI): 524 [M]+.

Aufarbeitung

  1. customIn a 250 mL flask was placed
  2. additionwas added
  3. waitAfter 4 h at rt
  4. washwashed 4 times with 250 mL of H2O
  5. washwashed once with 200 mL of brine
  6. dry with materialdried over NaSO4
  7. additionSilica gel was added
  8. customthe volatiles were removed under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-e764a5fe6999403c8ebc8e1e1fcc2243
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09233956B2

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