5-Chloro-N-(1,3-dioxo-1,3-dihydro-2-benzofuran-4-yl)-2-thiophenecarboxamide → 5-Chloro-N-(1,3-dioxo-2-{2-[4-(4-pyridinyl)piperazino]ethyl}-2,3-dihydro-1H-isoindol-4-yl)-2-thiophenecarboxamide

HRID 457742Notes

Reaction equation

HRID 457742 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][C:10]2[C:18]3[C:17](=[O:19])O[C:15](=[O:20])[C:14]=3[CH:13]=[CH:12][CH:11]=2)=[O:8])=[CH:4][CH:3]=1.[N:21]1[CH:26]=[CH:25][C:24]([N:27]2[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][NH2:35])[CH2:29][CH2:28]2)=[CH:23][CH:22]=1>C(O)(=O)C>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][C:10]2[CH:11]=[CH:12][CH:13]=[C:14]3[C:18]=2[C:17](=[O:19])[N:35]([CH2:34][CH2:33][N:30]2[CH2:29][CH2:28][N:27]([C:24]4[CH:25]=[CH:26][N:21]=[CH:22][CH:23]=4)[CH2:32][CH2:31]2)[C:15]3=[O:20])=[O:8])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 113926535-Chloro-N-(1,3-dioxo-1,3-dihydro-2-benzofuran-4-yl)-2-thiophenecarboxamide2×HCID 184406752-[4-(4-Pyridinyl)piperazino]ethylamine

Product 1

HCID 103003665-Chloro-N-(1,3-dioxo-2-{2-[4-(4-pyridinyl)piperazino]ethyl}-2,3-dihydro-1H-isoindol-4-yl)-2-thiophenecarboxamide

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

310 mg (1 mmol) of 5-chloro-N-(1,3-dioxo-1,3-dihydro-2-benzofuran-4-yl)-2-thiophenecarboxamide and 0.64 g (1 mmol) of 2-[4-(4-pyridinyl)piperazino]ethylamine (obtainable by heating 4-chloropyridine with aminoethylpiperazine or according to German Offenlegungschrift 2024350) are boiled in 40 ml of glacial acetic acid overnight. 340 mg of 5-chloro-N-(1,3-dioxo-1,3-dihydro-2-benzofuran-4-yl)-2-thiophenecarboxamide are added and the mixture is then boiled for another 24 h and subsequently concentrated under reduced pressure, water is added, the aqueous phase is extracted four times with ethyl acetate and the combined organic phases are dried with Na2SO4, admixed with silica gel and concentrated under reduced pressure. Chromatography on silica gel using a toluene/ethyl acetate→toluene/ethanol gradient gives 140 mg (28.2% of theory) of the target compound of m.p. 168° C. and Rf (SiO2, toluene/ethanol=1:1)=0.28.

Workup

  1. concentrationsubsequently concentrated under reduced pressure, water
  2. additionis added
  3. extractionthe aqueous phase is extracted four times with ethyl acetate
  4. dry with materialthe combined organic phases are dried with Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customChromatography on silica gel using a toluene/ethyl acetate→toluene/ethanol gradient gives 140 mg (28.2% of theory) of the target compound of m.p. 168° C. and Rf (SiO2, toluene/ethanol=1:1)=0.28

Sources & evidence

ORD record
ord-a4a44cf823a44a8d8fcf9dbd81a79f6d
Source dataset
uspto-grants-2007_03
Patent number
US07189738B2

Reaction notes

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