Potassium Carbonate → 6-(N-(3-Chloro-4-nitrophenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 1424792Notes

Reaction equation

HRID 1424792 reaction equation
[CH:1]1([C:4]2[C:5]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])=[CH:6][C:7]3[O:11][C:10]([C:12]4[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=4)=[C:9]([C:19]([NH:21][CH3:22])=[O:20])[C:8]=3[CH:23]=2)[CH2:3][CH2:2]1.[Cl:29][C:30]1[CH:35]=[C:34](F)[CH:33]=[CH:32][C:31]=1[N+:37]([O-:39])=[O:38].C(=O)([O-])[O-].[K+].[K+]>COCCOC.O>[Cl:29][C:30]1[CH:35]=[C:34]([N:24]([C:5]2[C:4]([CH:1]3[CH2:3][CH2:2]3)=[CH:23][C:8]3[C:9]([C:19]([NH:21][CH3:22])=[O:20])=[C:10]([C:12]4[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=4)[O:11][C:7]=3[CH:6]=2)[S:25]([CH3:28])(=[O:27])=[O:26])[CH:33]=[CH:32][C:31]=1[N+:37]([O-:39])=[O:38]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 750172-Chloro-4-fluoro-1-nitrobenzeneHCID 160735125-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-(methylsulfonamido)benzofuran-3-carboxamide

Product 1

HCID 1317322546-(N-(3-Chloro-4-nitrophenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamideYield 128.5%

Reagents, catalysts & solvents 1

HCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-(methylsulfonamido)benzofuran-3-carboxamide (12.5 g, 31.1 mmol), 2-chloro-4-fluoronitrobenzene (10.9 g, 62.1 mmol) and potassium carbonate (12.9 g, 93.0 mmol) in 130 mL of 4:1 DME/water in a sealed flask was heated to 100° C. with stirring. An identical 12.5 g scale reaction was set up in a second sealed vessel. The reaction vessels were maintained at 100° C. for 70 hours, cooled to RT, and stirred for an additional 18 hours. The combined reaction mixtures were partitioned between EtOAc (300 mL) and water (600 mL), and the phases separated. The aqueous solution was extracted with two additional 150 mL portions of EtOAc. The combined EtOAc solutions were washed with half saturated brine (1×), saturated brine (1×), dried over sodium sulfate and concentrated to dryness at reduced pressure. The resulting yellow-brown solid was recrystallized from EtOAc/ether to give the title compound (22.3 g, 64%) as an off-white solid. LCMS (m/z, ES+)=558 (M+H+).

Workup

  1. customAn identical 12.5 g scale reaction
  2. customwas set up in a second sealed vessel
  3. customThe reaction vessels
  4. temperaturewere maintained at 100° C. for 70 hours
  5. temperaturecooled to RT
  6. stirringstirred for an additional 18 hours
  7. customThe combined reaction mixtures
  8. customwere partitioned between EtOAc (300 mL) and water (600 mL)
  9. customthe phases separated
  10. extractionThe aqueous solution was extracted with two additional 150 mL portions of EtOAc
  11. washThe combined EtOAc solutions were washed with half saturated brine (1×), saturated brine (1×)
  12. dry with materialdried over sodium sulfate
  13. concentrationconcentrated to dryness at reduced pressure
  14. customThe resulting yellow-brown solid was recrystallized from EtOAc/ether

Sources & evidence

ORD record
ord-d26be72c3ab8482b9eef0b208ee5f39b
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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