Sodium Iodide → 3-{[3-Cyano-5-cyclopropyl-2-(4-fluorophenyl)-1-benzofuran-6-yl](methylsulfonyl)amino}propane-1-sulfonamide

HRID 705356Notes

Reaction equation

HRID 705356 reaction equation
[C:1]([C:3]1[C:7]2[CH:8]=[C:9]([CH:17]3[CH2:19][CH2:18]3)[C:10]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])=[CH:11][C:6]=2[O:5][C:4]=1[C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)#[N:2].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:34][CH2:35][CH2:36][S:37]([NH2:40])(=[O:39])=[O:38].[I-].[Na+]>CS(C)=O.C(OCC)(=O)C>[C:1]([C:3]1[C:7]2[CH:8]=[C:9]([CH:17]3[CH2:18][CH2:19]3)[C:10]([N:12]([S:13]([CH3:16])(=[O:15])=[O:14])[CH2:34][CH2:35][CH2:36][S:37]([NH2:40])(=[O:39])=[O:38])=[CH:11][C:6]=2[O:5][C:4]=1[C:20]1[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=1)#[N:2]

Participants

7

Reactant 4

HCID 5238Sodium Iodide3×HCID 11430Potassium Carbonate3×HCID 136148183-Chloropropane-1-sulfonamide3×HCID 89955206N-[3-cyano-5-cyclopropyl-2-(4-fluorophenyl)-1-benzofuran-6-yl]methanesulfonamide

Product 1

HCID 679813243-{[3-Cyano-5-cyclopropyl-2-(4-fluorophenyl)-1-benzofuran-6-yl](methylsulfonyl)amino}propane-1-sulfonamideYield 64.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of Example 11A (0.150 g, 0.405 mmol) in dry dimethyl sulfoxide (1.3 mL) under a nitrogen atmosphere was treated with potassium carbonate (0.090 g, 0.648 mmol), and the bright yellow mixture was stirred at room temperature for 30 minutes. Then 3-chloropropane-1-sulfonamide (0.096 g, 0.607 mmol) and sodium iodide (0.091 g, 0.607 mmol) were added, and the resultant mixture was heated at 50° C. for 22 hours. Additional potassium carbonate (0.090 g, 0.648 mmol), 3-chloropropane-1-sulfonamide (0.096 g, 0.607 mmol) and sodium iodide (0.091 g, 0.607 mmol) were added and stirring was continued at 50° C. for 23 hours. The reaction was incomplete by LCMS, so additional potassium carbonate (0.090 g, 0.648 mmol), 3-chloropropane-1-sulfonamide (0.096 g, 0.607 mmol) and sodium iodide (0.091 g, 0.607 mmol) were added followed by continued stirring at 50° C. for 22 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (50 mL), and washed with water (3×25 mL) and brine (10 mL). The organic phase was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. Purification by silica gel flash chromatography (10 g) eluting with 3% methanol/dichloromethane followed by trituration with diethyl ether (3×5 mL) afforded the title compound as white solid (0.128 g, 64%). MS (ESI+) m/z 509 (M+NH4)+, (ESI−) m/z 490 (M−H)−.

Workup

  1. stirringstirring
  2. waitwas continued at 50° C. for 23 hours
  3. additionwere added
  4. stirringby continued stirring at 50° C. for 22 hours
  5. temperatureThe reaction mixture was cooled to room temperature
  6. washwashed with water (3×25 mL) and brine (10 mL)
  7. dry with materialThe organic phase was dried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by silica gel flash chromatography (10 g)
  11. washeluting with 3% methanol/dichloromethane

Sources & evidence

ORD record
ord-0fd3bb2a42814e95b8280ed75170940c
Source dataset
uspto-grants-2015_11
Patent number
US09173887B2

Reaction notes

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