Sodium Bicarbonate → 4-[5-(4-Chlorophenyl)-2-thiophenesulfonyl]-1-[1-(4-pyridyl)piperidin-4-ylmethyl]-2-piperazinone

HRID 1840576Notes

Reaction equation

HRID 1840576 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13][C:12]([S:14]([N:17]3[CH2:22][CH2:21][N:20]([CH2:23][CH:24]4[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]4)[C:19](=[O:30])[CH2:18]3)(=[O:16])=[O:15])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.Cl.Cl[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=1.C(=O)(O)[O-].[Na+]>>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13][C:12]([S:14]([N:17]3[CH2:22][CH2:21][N:20]([CH2:23][CH:24]4[CH2:29][CH2:28][N:27]([C:37]5[CH:36]=[CH:35][N:34]=[CH:33][CH:38]=5)[CH2:26][CH2:25]4)[C:19](=[O:30])[CH2:18]3)(=[O:16])=[O:15])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1

Participants

4

Reactant 3

HCID 516892Sodium BicarbonateHCID 156199202-Chloropyridine--hydrogen chloride (1/1)HCID 234473094-[5-(4-Chlorophenyl)-2-thiophenesulfonyl]-1-(piperidin-4-ylmethyl)-2-piperazinone hydrochloride

Product 1

HCID 234474724-[5-(4-Chlorophenyl)-2-thiophenesulfonyl]-1-[1-(4-pyridyl)piperidin-4-ylmethyl]-2-piperazinone

Conditions

Temperature
130 °C

Procedure

To 1-[1-(tert-butoxycarbonyl)piperidin-4-ylmethyl]-4-[5-(4-chlorophenyl)-2-thiophenesulfonyl]-2-piperazinone (115 mg) were added 4N hydrochloric acid in ethyl acetate (10 ml) and methanol (4 ml), and the mixture was stirred at room temperature for 30 minutes. The reaction solution was concentrated to give crude crystals of 4-[5-(4-chlorophenyl)-2-thiophenesulfonyl]-1-(piperidin-4-ylmethyl)-2-piperazinone hydrochloride. A mixture of the obtained 4-[5-(4-chlorophenyl)-2-thiophenesulfonyl]-1-(piperidin-4-ylmethyl)-2-piperazinone hydrochloride and chloropyridine hydrochloride (85 mg) was added to sodium bicarbonate solution, and the mixture was extracted with dichloromethane (twice), dried and concentrated. To the residue was added isoamylalcohol (10 ml), and the mixture was stirred at 130° C. for 15 hours. The reaction solution was concentrated, and the residue was dissolved in dichloromethane. The solution was washed with 1 N sodium hydroxide solution, dried and concentrated, and the residue was purified with silica gel column chromatography (dichloromethane: methanol containing 10% ammonia solution 10:1) to give colorless solid of the title compound (42 mg).

Workup

  1. extractionthe mixture was extracted with dichloromethane (twice),
  2. customdried
  3. concentrationconcentrated
  4. additionTo the residue was added isoamylalcohol (10 ml)
  5. concentrationThe reaction solution was concentrated
  6. dissolutionthe residue was dissolved in dichloromethane
  7. washThe solution was washed with 1 N sodium hydroxide solution
  8. customdried
  9. concentrationconcentrated
  10. customthe residue was purified with silica gel column chromatography (dichloromethane: methanol containing 10% ammonia solution 10:1)

Sources & evidence

ORD record
ord-c21a5bc407fd4ff387e3a279dcd5f1a2
Source dataset
uspto-grants-2004_01
Patent number
US06680312B2

Reaction notes

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