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

Participants

Reaction Steps

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.

Provenance & Evidence