198704-99-3

Upstream product

• 19013-10-6 ethyl 4-hydroxy-3-nitrobenzoate 
• 108-24-7 acetic anhydride 
• 4334-88-7 p-ethoxycarbonylphenylboronic acid 
• 359446-50-7 2-methyl-benzoxazole-5-carboxylic acid ethyl ester 
• 64-19-7 acetic acid 
• 64-17-5 ethanol 

Downstream Products

• 1222172-51-1 ethyl 5-acetamido-2-amino-4-ethoxybenzoate 
• 1269662-90-9 N⁴-(3-chloro-4-fluorophenyl)-7-ethoxyquinazoline-4,6-diamine 
• 780821-04-7 ethyl 3-acetamido-4-ethoxybenzoate 

Relevant academic research and scientific papers

Balancing reactivity and antitumor activity: heteroarylthioacetamide derivatives as potent and time-dependent inhibitors of EGFR

Second- and third-generation inhibitors of EGFR possess an acrylamide group which alkylates Cys797, allowing to overcome resistance due to insurgence of T790M mutation. Less reactive warheads, yet capable to bind the target cysteine, may be useful to design newer and safer inhibitors. In the present work, we synthesized a 2-chloro-N-(4-(phenylamino)quinazolin-6-yl)acetamide (8) derivative as a prototype of EGFR inhibitor potentially able to react with Cys797 by nucleophilic substitution. We then tuned the reactivity of the acetamide fragment by replacing the chlorine leaving group with (hetero)-aromatic thiols or carboxylate esters. Among the synthesized derivatives, the 2-((1H-imidazol-2-yl)thio)acetamide 16, while showing negligible reactivity with cysteine in solution, caused long-lasting inhibition of wild-type EGFR autophosphorylation in A549 cells, resulted able to bind recombinant EGFR L858R/T790M in a time-dependent manner, and inhibited both EGFR autophosphorylation and proliferation in gefitinib-resistant H1975 lung cancer cells (expressing EGFR L858R/T790M mutant) at low micromolar concentration.

Cp?Rh(III)/Bicyclic Olefin Cocatalyzed C-H Bond Amidation by Intramolecular Amide Transfer

A bicyclic olefin was discovered as a cocatalyst in a Cp?Rh(III)-catalyzed C-H bond amidation proceeding by an intramolecular amide transfer in N-phenoxyacetamide derivatives. Combining experimental and theoretical studies, we propose that the olefin promotes a Rh(III) intermediate to undergo oxidative addition into the O-N bond to form a Rh(V) nitrenoid species and subsequently direct the nitrenoid to add to the ortho position. The amide directing group plays a dual role as a cleavable coordinating moiety as well as an essential coupling partner for the C-H amidation. This methodology was successfully applied to the late-stage diversification of natural products and a marketed drug under mild conditions.