An efficient solid phase one port synthesis of Novel triazolo[1,5-a]pyrimidine derivatives from 4-(4-aminophenyl)morpholin-3-one and evaluation of their antimicrobial activity

A series of novel triazolo[1,5-a]pyrimidine derivatives was synthesized from 5-amino-1,2,4-triazole and biologically active morpholinone amine in excellent yield as promising class of antimicrobial agents. The antimicrobial activities were investigated against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus pyogen, Candida albicans, Aspergillusniger, Aspergillusclavatus and compared with standard drugs Ampicillin, Chloramphenicol, Norfloxacin and Griseofulvin. All the synthesized compounds were characterized by IR, 1 H NMR, 13 C and mass spectroscopy. The result of antimicrobial activity data revealed that compound 4f,4g and 4i were found more active against bacterial species and compound 4c, 4d, 4g, 4i and 4jwere found more active against fungal strain, while other compounds shows moderate to law activity against microbes.

International Letters of Chemistry, Physics and Astronomy Vol. 33 13

Biology:
All the synthesized compounds were tested against different bacterial and fungal strains i.e. Pseudomonas aeruginosa, Proteus vulgaris, Escherichia Coli, Staphylococcus aureus, Candida albicanfor their in vitro antibacterial activity.Well Diffusion/Agar Cup Method was usedand results are listed in Table 2. The investigation of antibacterial and antifungal screening data revealed that all the tested compounds 4a-t showed moderate to potent activity. The compounds 4f, 4g and 4i showedcomparatively good activity against all the bacterial strains.

1. Experimental
Thin-layer chromatography was accomplished on 0.2-mm precoated plates of silica gel G60 F 254 (Merck). Visualization was made with UV light (254 and 365 nm) or with an iodine vapor. IR spectra were recorded on a FTIR-8400 spectrophotometer using DRS prob. 1 H (400 MHz) and 13 C (400 MHz) NMR spectra were recorded on a Bruker AVANCE II spectrometer in DMSO. Chemical shifts are expressed in δ ppm downfield from TMS as an internal standard. Mass spectra were determined using direct inlet probe on a GCMS-QP 2010 mass spectrometer (Shimadzu). Solvents were evaporated with a BUCHI rotary evaporator. Melting points were measured in open capillaries and are uncorrected.

1. General procedure for the synthesis of substituted triazolopyrimidines (4a-t)
A mixture of the aminoazole (0.01 mol), 4-methyl-3-oxo-N-(4-(3-oxomorpholino) phenyl)pentanamide (0.01 mol) 2a and an appropriate aromatic aldehyde (0.01 mol) 3a-t was fused in presence of trace amount of DMF for 12-15 min. After cooling, methanol (~10 mL) was added. The reaction mixture was allowed to stand overnight and then filtered to give the solid triazolopyrimidine products 4a-t, which were crystallized from ethanol and subsequently dried in air.               N-(4-(3-oxomorpholino)      than many other methods. According to Lt. General Raghunath the well technique is 5-6 times more sensitive than using disk method.

CONCLUSION
In summary, we have described the synthesis of substituted triazolopyrimidine derivatives in moderate yield. The reaction of various aldehydes with acetoacetamide and 5amino-1,2,4-triazole was afforded the triazolopyrimidine derivatives in moderate to good yield. All the synthesized compounds were evaluated for their antimicrobial activity. The investigation of antibacterial and antifungal screening data revealed that all the tested compounds 4a-t showed moderate to potent activity. The compounds 4f, 4g and 4iare found comparatively good active against all the bacterial strains.