Pyridine → N-[3-[5-(2-Chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-(methyloxy)phenyl]-2,6-difluorobenzenesulfonamide

HRID 239350Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 239350
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([CH:13]([CH3:15])[CH3:14])=[N:10][C:9]=2[C:16]2[C:17]([O:23][CH3:24])=[C:18]([CH:20]=[CH:21][CH:22]=2)[NH2:19])[CH:5]=[CH:4][N:3]=1.N1C=CC=CC=1.[F:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=1[S:39](Cl)(=[O:41])=[O:40]>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([CH:13]([CH3:15])[CH3:14])=[N:10][C:9]=2[C:16]2[C:17]([O:23][CH3:24])=[C:18]([NH:19][S:39]([C:33]3[C:34]([F:38])=[CH:35][CH:36]=[CH:37][C:32]=3[F:31])(=[O:41])=[O:40])[CH:20]=[CH:21][CH:22]=2)[CH:5]=[CH:4][N:3]=1

Komponenten

5

Edukt 3

HCID 1049PyridineHCID 27342712,6-Difluorobenzenesulfonyl chlorideHCID 579898673-[5-(2-Chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-(methyloxy)aniline

Produkt 1

HCID 57990015N-[3-[5-(2-Chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-(methyloxy)phenyl]-2,6-difluorobenzenesulfonamideAusbeute 58,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 3-[5-(2-chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-(methyloxy)aniline (10 g, 28 mmol), in DCM (100 mL) was added pyridine (6.6 g, 83.7 mmol) and the mixture was cooled to 0° C. 2,6-Difluorobenzene-1-sulfonyl chloride (5.9 g, 27.9 mmol) in DCM (100 mL) was added dropwise to the mixture. The reaction was stirred at rt for 4 h. Then the reaction was washed with water (200 mL), and extracted with DCM (2×200 mL). The organic layer was washed with brine, dried over anhydrous NaSO4, filtrated and concentrated under reduced pressure to give the crude product, which was purified by column chromatography on silica gel (petroleum ether:DCM 1:1) to afford the title compound of Step H (8.7 g, 58.2% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.21 (d, J=5.6 Hz, 1H), 7.70-7.75 (m, 1H), 7.63-7.67 (br, 1H), 7.46-7.55 (m, 1H), 7.15-7.19 (m, 2H), 6.95-7.03 (m, 2H), 6.58 (d, J=5.6 Hz, 1H), 3.35-3.40 (m, 4H), 1.44 (d, J=6.4 Hz, 6H). m/z (ES+): 537 [M+H]+.

Aufarbeitung

  1. washThen the reaction was washed with water (200 mL)
  2. extractionextracted with DCM (2×200 mL)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous NaSO4
  5. filtrationfiltrated
  6. concentrationconcentrated under reduced pressure
  7. customto give the crude product, which
  8. customwas purified by column chromatography on silica gel (petroleum ether:DCM 1:1)

Quellen und Nachweise

ORD-Eintrag
ord-2778ac08c069461dbe408a92c4a78c4f
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642759B2

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