Microwave Assisted Prospective Synthesis of New 5-Arylidene Rhodanine Derivatives Bearing a 3-[4-(3-Aminopropyl)piperazin-1-yl]propyl Side Chain

Abstract

International audienceA series of (5Z) 5-arylidene 2-thioxo-1,3-thiazolidin-4-one derivs. 7(a-l) bearing a [4-(3-aminopropyl)piperazin-1-yl]propyl side chain in N-3 position was prepd. using a soln. phase protocol assisted by microwave dielec. heating. These new compds. were synthesized in four steps with overall yields ranging from 12 to 33% via a "one-pot two-steps" protocol based on Holmberg reaction followed by a stereocontrolled Knoevenagel condensation. The rhodanine intermediate 4' issued from Holmberg reaction under microwave was also isolated and identified by spectroscopic methods of anal. The twelve deprotected products 7(a-l) have been obtained with a Z-geometry about their exocyclic double bond. All N-Boc intermediates 6(a-l) and deprotected rhodanine derivs. 7(a-l) issued from trifluoroacetic acid treatment have been characterized by 1H, 13C and HRMS

A practical multi-step synthesis of ethyl N-functionalized $$\varvec{\upbeta }$$ β -amino benzimidazole acrylate derivatives as promising cytotoxic agents

“…Routes A and B involve the use of mono-protected diamines 7(a, b); we chose the N-Boc protecting group because it is effectively removed in acid conditions. Tert-butyl {2-[4-(3aminopropyl)pyperazin-1-yl]propyl}carbamate 7a and tert-butyl (3-aminopropyl)carbamate 7b were synthesized according to the literature [15,16]. Treatment of diamines 6a and 6b with di-tertbutyldicarbonate (Boc) 2 O in 1,4-dioxane at room temperature for 24 hours produced mainly mono-N-Boc protected diamines 7a (56% yield) and 7b (80% yield).…”

“…Compound 7a was prepared in 56% yield as a colorless oil according to a previous procedure developed in our laboratory [15]…”

“…Deprotection of N-Boc compounds 10(a-p) was realized according to a method of literature [15], which involved the use of a solution of 6M HCl in 1,4-dioxane. After acidic treatment and work-up, the desired hydrochloride salt 11 was dried under high vacuum (10 -2 Torr) at 25 °C, then was stocked at 4 °C under nitrogen.…”

“…Mp = 206-208 °C. 1 Preparation of ethyl {3-[(benzo [1,3]dioxol-5-ylmethyl)amino]propylamino}-2-(1H-benzimidazol-2yl)acrylate (12e) by reduction of ethyl 3-{3-[(benzo [1,3]dioxol-5-ylmethylene)amino]propylamino}-2-(1H-benzimidazol-2-yl)acrylate (15) Ethyl 3-{3-[(benzo [1,3]dioxol-5-ylmethylene)amino]propylamino}-2-(1H-benzimidazol-2yl)acrylate 15 (24.9 mg, 0.06 mmol., 1 equiv.) was solubilized in methanol (6-8 mL) under vigorous stirring (500 rpm) and cooled at 0 °C.…”