N-Methoxy-6,N-dimethyl-nicotinamide → 4-Chloro-N-[5-chloro-2-(6-methyl-pyridine-3-carbonyl)-pyridin-3-yl]-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide

HRID 418994

Reaktionsgleichung

Reaktionsgleichung von HRID 418994
Br[C:2]1[C:7]([N:8]([CH2:23][O:24][CH3:25])[S:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19]([F:22])([F:21])[F:20])[CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5]([Cl:26])=[CH:4][N:3]=1.C([Mg]Cl)(C)C.CON(C)[C:35](=[O:43])[C:36]1[CH:41]=[CH:40][C:39]([CH3:42])=[N:38][CH:37]=1>C1COCC1>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([S:9]([N:8]([C:7]2[C:2]([C:35]([C:36]3[CH:37]=[N:38][C:39]([CH3:42])=[CH:40][CH:41]=3)=[O:43])=[N:3][CH:4]=[C:5]([Cl:26])[CH:6]=2)[CH2:23][O:24][CH3:25])(=[O:11])=[O:10])=[CH:13][C:14]=1[C:19]([F:22])([F:21])[F:20]

Komponenten

5

Edukt 3

HCID 11367353N-Methoxy-6,N-dimethyl-nicotinamideHCID 57942086N-(2-Bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxvmethyl-3-trifluoromethyl-benzenesulfonamideHCID 178418918HCID 178418918, Verbindung

Produkt 1

HCID 579425544-Chloro-N-[5-chloro-2-(6-methyl-pyridine-3-carbonyl)-pyridin-3-yl]-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamideAusbeute 33,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of N-(2-bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (90 mg, 0.2 mmol) in 2.0 mL of THF under nitrogen atmosphere at −78° C. was added drop-wise 0.3 mL (0.6 mmol) of isopropylmagnesium chloride. The mixture was then stirred for 10 min at −78° C. followed by warming to room temperature and stirred at that temperature for 30 min. The mixture was cooled to 0° C. (ice water) and a solution of N-methoxy-6, N-dimethyl-nicotinamide (72 mg, 0.4 mmol) in 1 mL of THF was added. The mixture was stirred at room temperature for 3 hours, quenched with 1M HCl and neutralized with 1M NaOH until pH was 9. The mixture was extracted with ethyl acetate, dried and concentrated. The residue was purified by flash column (silica gel, 50% ethyl acetate in hexane) to afford 36 mg of 4-chloro-N-[5-chloro-2-(6-methyl-pyridine-3-carbonyl)-pyridin-3-yl]-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide as an off white solid. MS: (M+H)/z=534.0.

Aufarbeitung

  1. temperatureby warming to room temperature
  2. stirringstirred at that temperature for 30 min
  3. stirringThe mixture was stirred at room temperature for 3 hours
  4. customquenched with 1M HCl and neutralized with 1M NaOH until pH was 9
  5. extractionThe mixture was extracted with ethyl acetate
  6. customdried
  7. concentrationconcentrated
  8. customThe residue was purified by flash column (silica gel, 50% ethyl acetate in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-24e53151dda7446581e9d57fc2bd9779
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093247B2

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