Nitromethane → HCID 86653260, compound

HRID 2196648Notes

Reaction equation

HRID 2196648 reaction equation
[Cl-].[Cl-].[Cl-].[Al+3].C[N+]([O-])=O.[F:9][C:10]1[C:27]([NH:28][S:29]([CH2:32][CH2:33][CH3:34])(=[O:31])=[O:30])=[CH:26][CH:25]=[C:24]([F:35])[C:11]=1[C:12]([NH:14][C:15]1[CH:16]=[C:17]2[CH:23]=[CH:22][NH:21][C:18]2=[N:19][CH:20]=1)=[O:13].[Cl:36][CH2:37][C:38](Cl)=[O:39]>C(Cl)Cl.[Cl-].[NH4+]>[Cl:36][CH2:37][C:38]([C:23]1[C:17]2[C:18](=[N:19][CH:20]=[C:15]([NH:14][C:12](=[O:13])[C:11]3[C:24]([F:35])=[CH:25][CH:26]=[C:27]([NH:28][S:29]([CH2:32][CH2:33][CH3:34])(=[O:31])=[O:30])[C:10]=3[F:9])[CH:16]=2)[NH:21][CH:22]=1)=[O:39]

Participants

7

Reactant 4

HCID 6375Nitromethane2×HCID 6577Chloroacetyl chloride2×HCID 6451240Aluminum(III) ChlorideHCID 441994082,6-difluoro-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide

Product 1

HCID 86653260HCID 86653260, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of aluminum trichloride (0.266 g, 2.00 mmol) in 1:1 DCM:CH3NO2 (5 mL) was added slowly 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 1:1 DCM:CH3NO2 (2 mL) at 0° C. The solution was stirred at 0° C. for 40 minutes. A solution of 2-chloroacetyl chloride (0.0307 mL, 0.380 mmol) in DCM (1 mL) was added, and the reaction mixture was allowed to warm to room temperature overnight. Additional 2-chloroacetyl chloride (5 eq.) was added, and the reaction mixture was warmed to 50° C. for 20 hours. The solution was cooled and diluted with saturated aqueous ammonium chloride and extracted with EtOAc (3 X). The organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. They were then purified via column chromatography (5% MeOH/DCM) to afford N-(3-(2-chloroacetyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-difluoro-3-(propylsulfonamido)benzamide (59 mg, 50%) as a solid.

Workup

  1. customat 0° C
  2. temperatureto warm to room temperature overnight
  3. temperaturethe reaction mixture was warmed to 50° C. for 20 hours
  4. temperatureThe solution was cooled
  5. extractionextracted with EtOAc (3 X)
  6. dry with materialThe organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThey were then purified via column chromatography (5% MeOH/DCM)

Sources & evidence

ORD record
ord-8ba30353c9bd4c4391a00059310848a0
Source dataset
uspto-grants-2012_12
Patent number
US08338452B2

Reaction notes

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