Indole → N-(4-fluoro-benzyl)-4-(3-iodo-indole-1-sulfonyl)-benzamide

HRID 737000Notes

Reaction equation

HRID 737000 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.CC(C)([O-])C.[K+].[I:16]I.S(Cl)(Cl)(=O)=O.[F:23][C:24]1[CH:43]=[CH:42][C:27]([CH2:28][NH:29][C:30]([C:32]2[CH:37]=[CH:36][C:35]([S:38](Cl)(=[O:40])=[O:39])=[CH:34][CH:33]=2)=[O:31])=[CH:26][CH:25]=1>CN(C=O)C>[F:23][C:24]1[CH:43]=[CH:42][C:27]([CH2:28][NH:29][C:30](=[O:31])[C:32]2[CH:37]=[CH:36][C:35]([S:38]([N:1]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[C:3]([I:16])=[CH:2]3)(=[O:40])=[O:39])=[CH:34][CH:33]=2)=[CH:26][CH:25]=1

Participants

7

Reactant 5

HCID 798IndoleHCID 807IodineHCID 24648Sulfuryl chlorideHCID 23665647Potassium tert-butoxide2×HCID 589751254-(4-Fluoro-benzylcarbamoyl)-benzenesulfonyl chloride

Product 1

HCID 58975061N-(4-fluoro-benzyl)-4-(3-iodo-indole-1-sulfonyl)-benzamideYield 52.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent4×

Procedure

Dissolve indole (2.93 g 0.025 mole) in 10 ml DMF. Cool the solution in an ice-water bath. Add potassium-t-butoxide (3.08 g, 0.0275 mole) and 10 ml DMF. Stir in an ice-bath for 22 minutes. Add iodine (7.61 g, 0.03 mole) and stir in an ice-bath for 12 minutes. Add the second shot of potassium-t-butoxide (3.08 g, 0.0275 mole) and 10 ml DMF. Add the appropriate sulfonyl chloride, 4-(4-fluoro-benzylcarbamoyl)-benzenesulfonyl chloride, (9.01 g, 0.0275 mole) and 10 ml DMF. Stir at ambient temperature for 16 hours. Quench the reaction with 100 ml water, and extract with ethyl acetate (3×150 ml). Wash the organics with sodium metabisulfate (10 g in 100 ml water), water (3×200 ml) and saturated brine (1×200 ml). Concentrate the organics and purify over silica gel using 20% ethyl acetate in heptane to obtain 6.96 g (yield=52.2%) of the desired product as an off-white solid: 1H NMR (DMSO): 9.2 (t, 1H), 8.1 (m, 3H), 8.0 (m, 3H), 7.4 (m, 5H), 7.1 (m, 2H), 4.4 (d, 4H). MS (ES−)=532.91 (M−1).

Workup

  1. temperatureCool the solution in an ice-water bath
  2. stirringStir at ambient temperature for 16 hours
  3. customQuench
  4. customthe reaction with 100 ml water
  5. extractionextract with ethyl acetate (3×150 ml)
  6. washWash the organics with sodium metabisulfate (10 g in 100 ml water), water (3×200 ml) and saturated brine (1×200 ml)
  7. concentrationConcentrate the organics and
  8. custompurify over silica gel using 20% ethyl acetate in heptane

Sources & evidence

ORD record
ord-32358a1e77e8412290229fd2fe68b098
Source dataset
uspto-grants-2009_09
Patent number
US07595339B2

Reaction notes

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