Hydrochloric Acid → 1-[(5-Chloroindol-2-yl)carbonyl]-4-[4-(pyridin-4-yl)phenylsulfonyl]piperazine Hydrochloride

HRID 352934Notes

Reaction equation

HRID 352934 reaction equation
Cl.C(O[C:7]([N:9]1[CH2:14][CH2:13][N:12]([S:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=3)=[CH:20][CH:19]=2)(=[O:17])=[O:16])[CH2:11][CH2:10]1)=[O:8])(C)(C)C.Cl.CO.[CH2:33]([Cl:35])[Cl:34].O1[CH2:40][CH2:39][CH2:38][CH2:37]1>CO>[ClH:34].[Cl:35][C:33]1[CH:37]=[C:38]2[C:26](=[CH:25][CH:24]=1)[NH:27][C:40]([C:7]([N:9]1[CH2:10][CH2:11][N:12]([S:15]([C:18]3[CH:19]=[CH:20][C:21]([C:24]4[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=4)=[CH:22][CH:23]=3)(=[O:16])=[O:17])[CH2:13][CH2:14]1)=[O:8])=[CH:39]2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 227099051-(tert-Butoxycarbonyl)-4-[4-(pyridin-4-yl)benzenesulfonyl]piperazineHCID 69881209Hydrochloric acid methanol methylene chloride tetrahydrofuran

Product 1

HCID 227104901-[(5-Chloroindol-2-yl)carbonyl]-4-[4-(pyridin-4-yl)phenylsulfonyl]piperazine Hydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A saturated solution of hydrochloride in methanol (10 ml) was added to 1-(tert-butoxycarbonyl)-4-[4-(pyridin-4-yl)phenylsulfonyl]piperazine (180 mg). After stirring for 30 minutes, the solvent was distilled off under reduced pressure. To a solution of the residue in N,N-dimethylformamide (10 ml) were added (5-chloroindol-2-yl)carboxylic acid (90.0 mg), 1-hydroxybenzotriazole (75.5 mg) and 1-(dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (107 mg) and diisopropylethylamine (233 μg) at room temperature. After stirring for 3 days, methylene chloride (100 ml) and water (500 ml) were added to the reaction mixture to separate it into layers. The water layer was extracted with methylene chloride (50 ml). The organic layers were combined, washed with water (500 ml) and a saturated aqueous solution (100 ml) of sodium bicarbonate, dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column (silica gel: 20 g, methylene chloride:acetone=3:1→1:1), whereby the title compound (97.5 mg) was obtained as a white solid. The resulting compound was dissolved in hydrochloric acid-methanol-methylene chloride-tetrahydrofuran, followed by concentration, whereby the title compound was obtained.

Workup

  1. distillationthe solvent was distilled off under reduced pressure
  2. additionTo a solution of the residue in N,N-dimethylformamide (10 ml) were added (5-chloroindol-2-yl)carboxylic acid (90.0 mg), 1-hydroxybenzotriazole (75.5 mg) and 1-(dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (107 mg) and diisopropylethylamine (233 μg) at room temperature
  3. stirringAfter stirring for 3 days
  4. additionmethylene chloride (100 ml) and water (500 ml) were added to the reaction mixture
  5. customto separate it into layers
  6. extractionThe water layer was extracted with methylene chloride (50 ml)
  7. washwashed with water (500 ml)
  8. dry with materiala saturated aqueous solution (100 ml) of sodium bicarbonate, dried over anhydrous sodium sulfate
  9. distillationdistilled under reduced pressure
  10. customto remove the solvent
  11. customThe residue was purified by chromatography on a silica gel column (silica gel: 20 g, methylene chloride:acetone=3:1→1:1), whereby the title compound (97.5 mg)
  12. customwas obtained as a white solid
  13. concentrationfollowed by concentration, whereby the title compound
  14. customwas obtained

Sources & evidence

ORD record
ord-4aff9fe61ac14e62bd8774d24c424c7e
Source dataset
uspto-grants-2004_06
Patent number
US06747023B1

Reaction notes

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