In the present study, compounds 13 and 14 are present predominately in the thioxo form as it was shown by the C=S band at 1,244–1,250 cm−1 in the FT-IR spectra of these compounds. Furthermore, the 1H NMR spectra of compounds 13 and 14 revealed clearly the absence of the signal originated from SH proton, instead of that, two signals due to NH proton on 1,2,4-triazol ring
was recorded at 10.45 (for 13) or 11.27 (for 14), that is characteristic for 4,5-dihydro-1H-1,2,4-triazoles. The synthesis of Mannich bases (15–17) was performed by the reaction of compounds 13 and 14 with 6-aminopenicillanic acid, 6-apa (for 17) or 7-aminocephalosporanic #Selleckchem LY2874455 randurls[1|1|,|CHEM1|]# acid, 7-aca (for 15 and 16) in tetrahydrofuran at room temperature in the presence of triethylamine and formaldehyde. The occurrence of the alkylaminomethylation was provided by the disappearance of signal for the proton at the N-1 nitrogen of the 1,2,4-triazole ring. Moreover, in 1H and 13C NMR spectra, additional signal corresponding to the 6-apa or 7-aca-ammonium salt was recorded at the
related chemical shift value. The conversion of arylcarbonothioylhydrazino side change to 4-chlorophenyl-3-phenyl-1,3-thiazole ring (18) was accomplished with the treatment of 4-chlorophenacyl bromide. This compound was characterized by spectroscopic techniques including 1H NMR, 13C NMR, FT-IR, EI-MS, and elemental analysis. The synthesis of ethyl arylidenehydrazino-piperazine-1-carboxylate derivatives (19a–c) was P505-15 mw performed by microwave irradiation of compound 9 with several aromatic aldehydes namely 3-hydroxy-4-methoxybenzaldehyde, pyridine-4-carbaldehyde, and 2-hydroxybenzaldehyde. In the FT-IR spectra of these arylidenehydrazino compounds, absorption bands characteristic for NH groups were visible in the ranges of 3,357–3,181 cm−1. Another piece of evidence for condensation was the appearance of a signal as singlet integrating for one proton in the 1H NMR spectra, which corresponds to the N=CH proton of azomethyne group. Moreover, these compounds gave mass fragmentation and elemental analysis confirming the proposed structures. Ethyl 4-(2-fluoro-4-[(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)methyl]amino
Nintedanib (BIBF 1120) phenyl)piperazine-1-carboxylate (20) was prepared from the reaction of compound 9 with CS2 in the basic media. The attempts for aminoalkylations of compound (20) by Mannich reaction allowed the isolation of the corresponding products (21 and 22) after 4 (for 21) or 6 h (for 22) at room temperature. This idea originated from the intent to introduce the penicillanic acid or cephalosporanic acid nucleus to (piperazin-1-yl)-2-thioxo-1,3,4-oxadiazole skeleton. As different from 20, the NMR spectra of the obtained Mannich bases (21 and 22) displayed additional signals derived from penicillanic- or cephalosporanic-acid moiety and –CH2—linkage at the related shift and integral values as D2O nonexchangeable signals.