3‐(3,5‐Dimethyl‐1H‐Pyrazol‐1‐yl)‐3‐Oxopropanenitrile as Precursor for Some New Mono‐Heterocyclic and Bis‐Heterocyclic Compounds

Abstract

3‐(3,5‐Dimethyl‐1 H ‐pyrazol‐1‐yl)‐3‐oxopropanenitrile 1 was used as a cyanoacetylating agent for synthesis of the acetanilide derivative 3. Compound 3 was utilized as a key intermediate for the synthesis of some new mono‐chromene and di‐chromene derivatives 9 and 13, the dihydrazo derivatives 15, and the dithiazole derivatives 18 via the condensation with o‐hydroxybenzaldehyde derivatives, the coupling with aryl diazonium salts, or the reaction with phenyl isothiocyanate in presence of KOH followed by phenacyl bromide derivatives respectively.

Ultrasonically Assisted N-Cyanoacylation and Synthesis of Alkyl(4-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)benzoyl)amino Acid Ester Derivatives

“…The ultrasonic method afforded the products in less reaction time with high yields and purities, as shown in Table . The spectral data of the products (Figures S2–S4, Supporting information) agreed with the reported data [ref for compound 6 : mp 225 °C, yield 91%; ref for compound 9 : 267–269 °C, yield 90%].…”

“…White solid in yields 88% (conventional heating, 4 h) and 95% (US, 20 min), mp 226–227 °C [ref : 225 °C, yield 91%]. 1 H NMR (400 MHz, DMSO- d 6 ) δ: 2.49 (s, 3H, CH 3 ), 3.92 (s, 2H, CH 2 ), 7.64 (d, 2H, J = 8.8 Hz, Ar), 7.42–7.91 (d, 2H, J = 8.8 Hz, Ar), 10.59 (s, 1H, NH) ppm; 13 C NMR (100 MHz, DMSO- d 6 ) δ: 26.5, 27.0, 115.6, 118.5, 129.7, 132.3, 142.6, 161.7, 197.6 ppm.…”

“…In the last few years, researchers have been involved in the exploration of the potential of activated nitriles in heterocyclic synthesis. − Especially, cyanoacetic hydrazide has been reported in many literature works as a good intermediate for the synthesis of numerous biologically active heterocyclic compounds and pharmaceutical agents. − …”

Design, Synthesis, Anticancer Evaluation and Molecular Modeling Studies of New Thiazolidinone‐Benzoate Scaffold as EGFR Inhibitors, Cell Cycle Interruption and Apoptosis Inducers in HepG2

“…Taking into account the aforementioned data and as an extension of our ongoing research work on the designing biologically active heterocyclic products that act as anticancer agents and others, [63–77] herein we adopted design and synthesis of new compounds containing thiazolidinone scaffold. Thiazolidinones 3 a , b were synthesized from the starting thiosemicarbazones 2 a , b , then 3 a , b undergoing Knövenagel condensation with different aryl and heteryl aldehydes by two‐steps or multicomponent route to afford three series of thiazolidinones 5 a – j , 7 a – h and 9 a – j bearing substitution at position‐5 as seen in Figure 3.…”

“…[60][61][62] On the other hand, Raslan et al [43] have reported synthesis of compounds containing benzoate moiety exhibiting better inhibition in HepG2 growth with IC 50 = 8.90 μM besides inhibiting EGFR protein kinase with IC 50 = 0.124 μM, in addition to a scientific article reported the synthesis of trimethoxy phenyl benzoate containing derivatives displaying anticancer activity and inhibitory activity against EGFR. [44] Taking into account the aforementioned data and as an extension of our ongoing research work on the designing biologically active heterocyclic products that act as anticancer agents and others, [63][64][65][66][67][68][69][70][71][72][73][74][75][76][77] herein we adopted design and synthesis of new compounds containing thiazolidinone scaffold. Thiazolidinones 3 a, b were synthesized from the starting thiosemicarbazones 2 a, b, then 3 a, b undergoing Knövenagel condensation with different aryl and heteryl aldehydes by two-steps or multicomponent route to afford three series of thiazolidinones 5 a-j, 7 a-h and 9 a-j bearing substitution at position-5 as seen in Figure 3.…”