Synthesis of 3‐amino‐2‐carbamoylthiophene and its reaction with cycloalkanones to form imines

Abstract

3‐Amino‐2‐carbamoylthiophene (2) was obtained in 75% yield by reaction of methyl 3‐aminothiophene‐2‐carboxylate with saturated aqueous ammonia containing ammonium chloride catalyst at room temperature over a period of 2,3 months, Treatment of 2 with cyclopentanone, cyclohexanone, and cycloheptanone in ethanol at pH 3.4 gave facile formation of 2‐carbamoyl‐3‐cycloalkylidenaminothiophenes in yields of 73%, 86%, and 60%, respectively. Infrared and 1H nmr spectra of these imines indicate that they occur in intramolecularly hydrogenbonded form, i.e. with chelate rings. Comparison is made with reported syntheses and reactions of 2 and its isosteric 2‐aminobenzamide.

Synthesis and characterization of 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide-based compounds targeting the PA-PB1 interface of influenza A virus polymerase

“…Through an analogous procedure, benzothiophene-2-carboxamide derivative 11 and thiophene-2-carboxamide derivatives 13 and 22 were prepared as reported in Scheme 4 , Scheme 5 , respectively. Thus, ethyl carboxylate derivative 46 [ 46 ], prepared by reacting 2-chlorobenzonitrile and ethyl thioglycolate in presence of KOH in DMF, and methyl 3-aminothiophene-2-carboxylate were reacted with hydrazine hydrate providing carbohydrazide derivatives 47 [ 47 ] and 49 [ 47 ], which were in turn treated with Ni-Raney to give carboxamide derivatives 48 [ 48 ] and 50 [ 49 ], respectively. Coupling reaction of 48 with 30 and 50 with 30 and 31 provided derivatives 11 , 13 and 22 , respectively.…”

“…[ 49 ] The title compound was prepared starting from methyl 3-aminothiophene-2-carboxylate through Method B providing 49 [ 47 ] in 100% yield, followed by Method C (overnight, purification by treatment with Et 2 O) in 20% yield; 1 H NMR (DMSO‑ d 6 , 400 MHz): δ 6.38 (s, 2H, NH 2 ), 6.52 (d, J = 4.8 Hz, 1H, thiophene CH), 6.81 (s, 2H, NH 2 ), 7.32 (d, J = 4.8 Hz, 1H, thiophene CH).…”

“…The title compound was prepared starting from 50 [ 49 ] and 31 [ 37 ] through Method A (overnight), worked up through procedure 1, and purified by flash chromatography eluting with MeOH/CHCl 3 (4%), in 36% yield as yellow solid; 1 H NMR (DMSO‑ d 6 , 400 MHz): δ 2.80 (s, 1H, CH 3 ), 7.50–7.60 (m, 4H, aromatic CH and CON H 2 ), 7.80 (d, J = 5.3 Hz, 1H, thiophene CH), 8.10 (s, 1H, H-6), 8.15 (d, J = 5.3 Hz, 1H, thiophene CH), 8.25–8.30 (m, 3H, aromatic CH and CON H 2 ), 12.90 (s, 1H, NHCO); 13 C NMR (DMSO‑ d 6 , 101 MHz): δ 17.3, 109.1, 114.9, 122.1, 127.9, 128.1, 129.5, 132.0, 136.2, 141.8, 149.5, 155.3, 156.4, 158.7, 161.7, 165.6; HRMS: m/z calcd for C 18 H 14 N 6 O 2 S 379.0977 (M + H) + , found 379.09724. HPLC, ret.…”

Preparation of a 7-Arylthieno[3,2-d]pyrimidin-4-Amine Library

“…The starting material 3-aminothiophene-2-carboxamide (1) is synthesized according to literature procedures. 9 Cyclization of compound 1 with formamide provides thieo [3,2-d]pyrimidin-4(3H)-one (2). The subsequent reaction of 2 with bromine, followed by phosphoryl trichloride, gives the key 7-bromo-4-chlorothieno [3,2-d]pyrimidine core structure (4).…”

“…The starting material 3-aminothiophene-2-carboxamide ( 1 ) is synthesized according to literature procedures . Cyclization of compound 1 with formamide provides thieo[3,2-d]pyrimidin-4(3 H )-one ( 2 ).…”