Acid-catalyzed reaction of ethyl cyanoformate with aromatic amines in acetic acid: facile synthesis of N-substituted amidinoformic acids and ethyl 4-quinazolone-2-carboxylate

Four Mechanisms in the Reactions of 3-Aminopyrrole with 1,3,5-Triazines: Inverse Electron Demand Diels–Alder Cycloadditions vs SNAr Reactions via Uncatalyzed and Acid-Catalyzed Pathways

“…The reaction of 3-aminopyrrole ( 1 ) with seven symmetrical 1,3,5-triazines 4 was carried out by generating the 3-aminopyrrole ( 1 ) in situ in two ways: a one-step reaction in which the reduction of 3-nitropyrrole ( 2 ) to 3-aminopyrrole ( 1 ), with Sn/acetic acid in CH 2 Cl 2 , was carried out in the presence of the 1,3,5-triazine 4 ; whereas, in the two-step procedure the 3-aminopyrrole ( 1 ) was generated in the presence of the 1,3,5-triazine 4 by treating the tetraphenylborate salt of 3-aminopyrrole ( 3 ) with an amine base in THF or the salt in CH 2 Cl 2 /AcOH.…”

“…13 C NMR were recorded at either 75 or 100 MHz using a proton-decoupled pulse sequence with a d 1 of 5 s, and are tabulated by observed peak. All of the triazines used in this work were commercially available except for 2,4,6-tricarbethoxy-1,3,5-triazine which was synthesized according to a literature procedure . The 3-nitropyrrole ( 2 ) used in this work was commercially available and the 1 H -pyrrol-3(2 H )-iminium tetraphenylborate ( 3 ) was synthesized according to a newly published procedure …”

Discovery of Novel, Highly Potent, and Selective Quinazoline-2-carboxamide-Based Matrix Metalloproteinase (MMP)-13 Inhibitors without a Zinc Binding Group Using a Structure-Based Design Approach

“…The ester group at the 2-position is highly reactive toward primary aliphatic amines to give the corresponding amide derivatives 9a – m . Common intermediates 8n and 8o were obtained from readily prepared anthranilic acid esters 15 in a single-step procedure (method B) employing ethyl cyanoformate and 1 M HCl/AcOH . Hydrolysis of the diester 10 by aqueous lithium hydroxide provided the corresponding monoacid 11 , which was homologated via the Arndt–Eistert sequence to give the methyl ester 12 (Scheme ) .…”

“…Common intermediates 8n and 8o were obtained from readily prepared anthranilic acid esters 15 in a single-step procedure (method B) employing ethyl cyanoformate and 1 M HCl/AcOH. 16 Hydrolysis of the diester 10 by aqueous lithium hydroxide provided the corresponding monoacid 11, which was homologated via the Arndt−Eistert sequence to give the methyl ester 12 (Scheme 2). 17 Catalytic reduction of the nitro group of 12 over palladium on carbon yielded the anthranilic acid ester 15a.…”