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

HRID 1455672Notes

Reaction equation

HRID 1455672 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][C:10]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:11]=2[C:12](=[O:24])[N:13]([CH2:20][C:21]([OH:23])=O)[C:14]3=[O:19])=[O:8])=[CH:4][CH:3]=1.O.O[N:27]1[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35]C=2N=N1.CN(C)CCCN=[C:42]=[N:43][CH2:44][CH3:45].[CH:47]([N:50](C(C)C)CC)(C)C>CN(C=O)C.O>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][C:10]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:11]=2[C:12](=[O:24])[N:13]([CH2:20][C:21](=[O:23])[N:43]2[CH2:42][CH2:47][N:50]([C:33]4[CH:32]=[CH:31][N:27]=[CH:35][CH:34]=4)[CH2:45][CH2:44]2)[C:14]3=[O:19])=[O:8])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 12074875HCID 12074875, compound

Product 1

HCID 99579765-Chloro-N-(1,3-dioxo-2-{2-oxo-2-[4-(4-pyridinyl)piperazino]ethyl}-2,3-dihydro-1H-isoindol-4-yl)-2-thiophenecarboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

0.43 g (1.18 mmol) of 2-(4-{[(5-chloro-2-thienyl)carbonyl]amino}-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid is dissolved in 15 ml DMF, 0.2 g (1.3 equivalents) 1-hydroxy-1H-benzotriazole hydrate (HOBT) and 0.238 g of N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDCI) (1.3 equivalents) are added and 0.305 g (0.411 ml; 2 equivalents) of diisopropylethylamine (DIEA) is added dropwise at room temperature over a period of 15 min. The mixture is stirred at room temperature overnight, the suspension turning into a clear solution. Water is then added to the reaction mixture, the aqueous phase is extracted three times with ethyl acetate, the combined organic phases are dried and concentrated under reduced pressure and the residue is coevaporated three times with toluene. The residue is suspended in toluene, filtered and washed with toluene. Drying gives 0.458 g (76.4% of theory) of the target compound of m.p. 207° C.

Workup

  1. extractionthe aqueous phase is extracted three times with ethyl acetate
  2. customthe combined organic phases are dried
  3. concentrationconcentrated under reduced pressure
  4. filtrationfiltered
  5. washwashed with toluene
  6. customDrying
  7. customgives 0.458 g (76.4% of theory) of the target compound of m.p. 207° C.

Sources & evidence

ORD record
ord-52150624677a4e4c878076a4bd1e8f84
Source dataset
uspto-grants-2009_01
Patent number
US07482472B2

Reaction notes

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