1-Hydroxybenzotriazole → [4-(1,1-Dioxo-1lambda6-isothiazolidin-2-yl)phenyl][4-(4-methylbenzoyl)piperidin-1-yl]methanone

HRID 2411466Notes

Reaction equation

HRID 2411466 reaction equation
[O:1]=[S:2]1(=[O:16])[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][CH:8]=1.Cl.[NH:18]1[CH2:23][CH2:22][CH:21]([C:24]([C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=2)=[O:25])[CH2:20][CH2:19]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(=O)([O-])O.[Na+]>CN(C)C=O.C(N(CC)CC)C>[O:16]=[S:2]1(=[O:1])[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:8]=[CH:9][C:10]([C:11]([N:18]2[CH2:23][CH2:22][CH:21]([C:24](=[O:25])[C:26]3[CH:27]=[CH:28][C:29]([CH3:32])=[CH:30][CH:31]=3)[CH2:20][CH2:19]2)=[O:13])=[CH:14][CH:15]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27408174-(4-Methylbenzoyl)piperidine hydrochlorideHCID 66250114-(1,1-Dioxo-1,2-thiazolidin-2-yl)benzoic acid

Product 1

HCID 71261250[4-(1,1-Dioxo-1lambda6-isothiazolidin-2-yl)phenyl][4-(4-methylbenzoyl)piperidin-1-yl]methanoneYield 24.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

4-(1,1-Dioxo-1λ6-isothiazolidin-2-yl)benzoic acid (253 mg) described in Preparation Example 16, (piperidin-4-yl) (p-tolyl)methanone hydrochloride (252 mg), 1-hydroxybenzotriazole 1 hydrate (142 mg) and triethylamine (0.15 mL) were dissolved in N,N-dimethylformamide (5 mL), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (202 mg) was added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added 5% aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and the solvent was evaporated. The obtained residue was purified by column chromatography (chloroform:methanol) to give the title compound (108 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine
  3. customthe solvent was evaporated
  4. customThe obtained residue was purified by column chromatography (chloroform:methanol)

Sources & evidence

ORD record
ord-54dcd11727aa4ebba5b8a60c12deff2f
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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