Benzenesulfonyl chloride → 3-(2,5-Dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole

HRID 1842678Notes

Reaction equation

HRID 1842678 reaction equation
CC(C)([O-])C.[Na+].[Cl:7][C:8]1[N:13]=[C:12]([C:14]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[NH:16][CH:15]=2)[C:11]([Cl:23])=[CH:10][N:9]=1.[C:24]1([S:30](Cl)(=[O:32])=[O:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CN(C=O)C>[C:24]1([S:30]([N:16]2[C:17]3[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:14]([C:12]3[C:11]([Cl:23])=[CH:10][N:9]=[C:8]([Cl:7])[N:13]=3)=[CH:15]2)(=[O:32])=[O:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

5

Reactant 3

HCID 7369Benzenesulfonyl chloride2×HCID 23676156Sodium t-butoxide2×HCID 566553763-(2,5-Dichloropyrimidin-4-yl)-1H-indole2×

Product 1

HCID 707007943-(2,5-Dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indoleYield 46%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium tert-butoxide (529 mg, 5.50 mmol) was added portionwise over a period of 2 minutes to a mixture of 3-(2,5-dichloro-pyrimidin-4-yl)-1H-indole (Intermediate 11, 1.321 g, 5.0 mmol) and benzenesulfonyl chloride (0.645 mL, 5.00 mmol) in DMF (30 mL) at r.t. under N2. The resulting solution was stirred at r.t. for 1 h. Further benzenesulfonyl chloride (0.064 mL, 0.50 mmol) and sodium tert-butoxide (0.053 g, 0.055 mmol) were added and the mixture was stirred at r.t. for a further 0.25 h. The reaction was quenched by the addition of CH3OH (6 mL) and neutralised by the addition of solid CO2 pellets until reaching pH=7. The solvent was then removed in vacuo and the resulting residue was dissolved in CH2Cl2 (100 mL). This solution was filtered through a 20 g silica pad, and the eluted solution was diluted with isohexane (50 mL). This solution was concentrated in vacuo to give a volume of 70 mL and was then cooled. A resulting crystalline precipitate was collected by filtration, washed with isohexane/CH2Cl2 (4:1, 50 mL) and dried by suction to give the title compound (923 mg, 46%) as an off-white crystalline solid, which was used without further purification; 1H NMR: 7.39-7.53 (2H, m), 7.64 (2H, t), 7.75 (1H, t), 8.04 (1H, d), 8.11-8.17 (2H, m), 8.28 (1H, d), 8.79 (1H, s), 9.00 (1H, s); m/z: ES+ MH+ 404.

Workup

  1. stirringthe mixture was stirred at r.t. for a further 0.25 h
  2. customThe reaction was quenched by the addition of CH3OH (6 mL)
  3. additionneutralised by the addition of solid CO2 pellets
  4. customThe solvent was then removed in vacuo
  5. dissolutionthe resulting residue was dissolved in CH2Cl2 (100 mL)
  6. filtrationThis solution was filtered through a 20 g silica pad
  7. additionthe eluted solution was diluted with isohexane (50 mL)
  8. concentrationThis solution was concentrated in vacuo
  9. customto give a volume of 70 mL
  10. temperaturewas then cooled
  11. filtrationA resulting crystalline precipitate was collected by filtration
  12. washwashed with isohexane/CH2Cl2 (4:1, 50 mL)
  13. customdried by suction

Sources & evidence

ORD record
ord-83b4e0be999a40469026172688cba628
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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