Condensations of isatinic acid with ureas, ethyl carbamate and guanidine

Abstract

By condensing the potassium salt of isatinic acid -(0-aminopheny1)-glyoxylic acid -with urea, A;-substituted ureas and ethyl carbamate, 2-hydroxyquinazoline-4-carboxylic acid was obtained, in excellent yield. In a similar condensation with guanidine, potassium isatinate reacted quantitatively t o give 2-aminoquinazoline-4-carboxylic acid. Various derivatives were obtained from these new acids by methylation and decarboxylation reactions.Only a small number of 2-alkyl-and 2-aryl-quinazoline-4-carboxylic acids (11) are known 192. They were all prepared in the same way, i.e. by condensing ammonia with N-acylated isatinic acids (I). When reported, the over-all yields -starting from isatins or o-aminoacetophenone -appear to be rather low. Quinazoline-4-carboxylic acid itself has not been synthesized hitherto.

Scouting Human A3 Adenosine Receptor Antagonist Binding Mode Using a Molecular Simplification Approach: From Triazoloquinoxaline to a Pyrimidine Skeleton as a Key Study

“…An excess of 2-aminoquinazoline-4-carboxylic acid (2.64 mmol) was reacted with the amines 19 , 21 – 23 (0.88 mmol), and 20 (1.32 mmol), in the presence of 1-(3-(dimethylamino)propyl))-3-ethyl-carbodiimide hydrochloride (2.64 mmol), 1-hydroxybenzotriazole (2.64 mmol), triethylamine (4.4 mmol), and 4-(dimethylamino)pyridine (0.08 mmol) in anhydrous dimethylformamide (2–3 mL). The mixture was stirred at room temperature for 26 h (compound 3 ), 96 h (compounds 1 , 4 , and 5 ), and 168 h (compound 2 ).…”

“…The quinazoline-4-carboxamido derivatives 1 – 11 , their 3-deaza analogues quinoline-4-carboxamides 12 – 15 , and the pyrimidine-4-carboxamides 16 – 18 were obtained as depicted in Schemes and . Scheme showed the straightforward synthesis of the 2-amino-quinazoline-4-carboxamido derivatives 1 – 5 and the 2-oxo-quinazoline-4-carboxamido derivatives 6 – 9 , which were prepared by coupling the corresponding 2-amino- and 2-oxo-quinazoline-4-carboxylic acids with the suitable amines 19 – 23 (Scheme ). By reaction of the 2-amino-quinazoline-4-carboxyanilide 2 with acetyl and benzoyl chloride, the 2-amido-quinazoline-4-carboxyamides 10 and 11 were obtained, respectively.…”

“…Yield, 22%; mp 176-177 °C (EtOH); 1 General Procedure for the Synthesis of 2-Oxoquinazoline-4carboxamido Derivatives 6-9. An excess of 2-oxoquinazoline-4carboxylic acid 25 (2.64 mmol) was reacted with the amines 19, 21, 22 (0.88 mmol), and 20 (0.59 mmol) in the presence of 1-(3-(dimethylamino)propyl))-3-ethyl-carbodiimide hydrochloride (2.64 mmol), 1-hydroxybenzotriazole (2.64 mmol), triethylamine (4.4 mmol), and 4-(dimethylamino)pyridine (0.08 mmol) in anhydrous dioxane (5 mL, derivative 7) or anhydrous dimethylformamide (2-3 mL, compounds 6, 8, 9). The mixture was stirred at room temperature for 4 h (compound 6), 24 h (compound 8), 72 h (compound 9), or 168 h (compound 7) The title compounds were obtained by different workup of the reaction mixtures.…”

Esters of Carbamic Acid

“…Quinazoline-4-carboxylic acids (CCI) are formed when unsubstituted carbamates react with salts of isatic acid (CCII) (derived from isatin by caustic treatment) (318).…”