Trifluoroacetic acid → [2-(3-Aminopropoxy)-4-(1,1-dioxo-1lambda6-isothiazolidin-2-yl)phenyl][4-(2,4-dimethylphenyl)piperazin-1-yl]methanone

HRID 2411587Notes

Reaction equation

HRID 2411587 reaction equation
C(OC(=O)[NH:7][CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[C:16]([N:18]2[CH2:22][CH2:21][CH2:20][S:19]2(=[O:24])=[O:23])[CH:15]=[CH:14][C:13]=1[C:25]([N:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][C:34]=2[CH3:40])[CH2:29][CH2:28]1)=[O:26])(C)(C)C.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+]>ClCCl>[NH2:7][CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[C:16]([N:18]2[CH2:22][CH2:21][CH2:20][S:19]2(=[O:23])=[O:24])[CH:15]=[CH:14][C:13]=1[C:25]([N:27]1[CH2:28][CH2:29][N:30]([C:33]2[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][C:34]=2[CH3:40])[CH2:31][CH2:32]1)=[O:26]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 71252727(3-{2-[4-(2,4-Dimethylphenyl)piperazine-1-carbonyl]-5-(1,1-dioxo-1lambda6-isothiazolidin-2-yl)phenoxy}propyl)carbamic acid tert-butyl ester

Product 1

HCID 71252809[2-(3-Aminopropoxy)-4-(1,1-dioxo-1lambda6-isothiazolidin-2-yl)phenyl][4-(2,4-dimethylphenyl)piperazin-1-yl]methanoneYield 40.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of [4-(2,4-dimethylphenyl)piperazin-1-yl][4-(1,1-dioxo-1λ6-isothiazolidin-2-yl)-2-hydroxyphenyl]methanone (241 mg) described in Example 124, (3-bromopropyl)carbamic acid tert-butyl ester (200 mg) and cesium carbonate (548 mg) was added 2-butanone (4 mL), and the mixture was stirred with heating under reflux for 4 hr. Water was added to the reaction mixture, the mixture was extracted with ethyl acetate, and the solvent was evaporated. The obtained residue was purified by column chromatography (ethyl acetate:hexane) to give (3-{2-[4-(2,4-dimethylphenyl)piperazine-1-carbonyl]-5-(1,1-dioxo-1λ6-isothiazolidin-2-yl)phenoxy}propyl)carbamic acid tert-butyl ester (221 mg). The obtained (3-{2-[4-(2,4-dimethylphenyl)piperazine-1-carbonyl]-5-(1,1-dioxo-1λ6-isothiazolidin-2-yl)phenoxy}propyl)carbamic acid tert-butyl ester (221 mg) was dissolved in dichloromethane (2 mL), trifluoroacetic acid (0.46 mL) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was poured into ice water, the mixture was neutralized with sodium hydrogen carbonate and extracted with chloroform, and the solvent was evaporated. The obtained residue was purified by NH-coated silica gel column chromatography (ethyl acetate:methanol) to give the title compound (74 mg).

Workup

  1. extractionextracted with chloroform
  2. customthe solvent was evaporated
  3. customThe obtained residue was purified by NH-coated silica gel column chromatography (ethyl acetate:methanol)

Sources & evidence

ORD record
ord-c2740467730c475e814a2c0527ff9674
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

Loading…