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

HRID 2196658Notes

Reaction equation

HRID 2196658 reaction equation
[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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-c07b929de1dd4922ab814866fa819d12
Source dataset
uspto-grants-2012_12
Patent number
US08338452B2

Reaction notes

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