Acetyl chloride → N-(3-acetyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-difluoro-3-(propylsulfonamido)benzamide

HRID 2196658Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2196658
[Cl-].[Cl-].[Cl-].[Al+3].[F:5][C:6]1[C:23]([NH:24][S:25]([CH2:28][CH2:29][CH3:30])(=[O:27])=[O:26])=[CH:22][CH:21]=[C:20]([F:31])[C:7]=1[C:8]([NH:10][C:11]1[CH:12]=[C:13]2[CH:19]=[CH:18][NH:17][C:14]2=[N:15][CH:16]=1)=[O:9].[C:32](Cl)(=[O:34])[CH3:33].C[N+]([O-])=O>C(Cl)Cl>[C:32]([C:19]1[C:13]2[C:14](=[N:15][CH:16]=[C:11]([NH:10][C:8](=[O:9])[C:7]3[C:20]([F:31])=[CH:21][CH:22]=[C:23]([NH:24][S:25]([CH2:28][CH2:29][CH3:30])(=[O:27])=[O:26])[C:6]=3[F:5])[CH:12]=2)[NH:17][CH:18]=1)(=[O:34])[CH3:33]

Komponenten

6

Edukt 4

HCID 6367Acetyl chlorideHCID 6375NitromethaneHCID 6451240Aluminum(III) ChlorideHCID 441994082,6-difluoro-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide

Produkt 1

HCID 44223281N-(3-acetyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-difluoro-3-(propylsulfonamido)benzamideAusbeute 64 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A slurry of aluminum trichloride (0.270 g, 2.03 mmol) was added to a slurry of 2,6-difluoro-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide (0.100 g, 0.254 mmol) in DCM (0.7 mL) at 0° C., and the reaction mixture was allowed to stir at 0° C. for 40 minutes. Acetyl chloride (0.0271 mL, 0.380 mmol) was added, and the mixture was allowed warm to room temperature overnight. CH3NO2 (200 μL) was added, and the reaction mixture was sonicated for 2 minutes, and allowed to stir at room temperature overnight. The reaction mixture was quenched with ice and then partitioned between aqueous sodium bicarbonate and EtOAc. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified via column chromatography (5% MeOH/EtOAc) to yield N-(3-acetyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-difluoro-3-(propylsulfonamido)benzamide (71 mg, 64%) as a solid. 1H NMR (400 MHz, CDCl3) δ 8.98-8.99 (m, 1H), 8.63-8.64 (m, 1H), 8.04 (s, 1H), 7.49-7.54 (m, 1H), 7.15-7.18 (m, 1H), 3.10-3.30 (m, 2H), 2.55 (s, 3H), 1.93-2.00 (m, 2H), 1.09-1.13 (m, 3H); m/z (APCI-pos) M+1=437.1.

Aufarbeitung

  1. temperaturethe mixture was allowed warm to room temperature overnight
  2. customthe reaction mixture was sonicated for 2 minutes
  3. stirringto stir at room temperature overnight
  4. customThe reaction mixture was quenched with ice
  5. custompartitioned between aqueous sodium bicarbonate and EtOAc
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified via column chromatography (5% MeOH/EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-c07b929de1dd4922ab814866fa819d12
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08338452B2

Notizen zur Reaktion

Wird geladen…