Synthesis and spectral characterization of some new thiazolopyrimidine derivatives

Thiazolopyrimidnes are considered one of the most interesting classes in heterocyclic chemistry due to their pharmaceutical importance. Herein, we report the synthesis of some new heterocyclic compounds containing thiazolopyrimidine starting from compound (1) which was previously prepared in literature. The starting compound was allowed to react with different alkylating agents such as chloroacetone, chloroacetyl chloride


Introduction
2][3] Thiazolopyrimidine is one of the most interesting heterocyclic scaffolds possessing structural similarity to 5-fluorouracil (5-FU)-the well-known cancer metabolite.3][24] Accordingly, and in continuation of our ongoing interest regarding the synthesis of biologically active molecules containing nitrogen and sulphur heteroatom,  we report here a convenient and efficient method for the synthesis of several novel derivatives including pyrimidine building block.

Results and Discussion
As shown in Fig. 1, in the alkylation of compound 1, which prepared according to reported procedure, 52 with different alkylating agents such as chloroacetyl chloride, chloroacetone and phenacyl bromide, the alkylation of mercapto group was occurred to produce the S-alkylated products 2-4.The structure of the new obtained compounds was confirmed by the elemental and spectral analysis where the IR spectrum of compound 2 showed two C=O groups 1663, 1655 cm -1 while the 1 H NMR spectrum showed singlet signal at 4.37 ppm characteristic for CH2 group.In addition, the 1 H NMR spectrum of compound 4 showed multiplet signals at 7-8 ppm, which proved the introduction of additional phenyl rings.

Fig. 1. Synthesis of compounds 2-4.
As shown in Fig. 2, condensation of compound 2 with benzaldehyde gave a cyclic chalcone derivative 5 which in turn reacted with malononitrile to give the amino-dicarbonitrile compound 6.After that, acetylation of the amino group in compound 6 with chloroacetyl chloride led to the formation of 2-Chloro-N-(3,8-dicyano-7-oxo-4,9-diphenyl-5a,6-dihydro-4H,7H-pyrano[2',3':4,5]thiazolo[3,2a]pyrimidin-2-yl)acetamide compound (7).When the latter compound was allowed to react with aniline, nucleophilic substitution occurred to produce compound 8, which reacted with formaldehyde under Munich condition to give compound 9.The structure of the obtained compounds was easily confirmed by the spectral analysis where the 1 H NMR spectrum of compound 5 showed two singlet signals at 3.88 and 5.93 ppm characteristic for CH=CH protons as well as increasing the aromatic protons by 5H.Also, the IR spectrum of compound 6 showed the appearance of two bands at 3321, 3245 cm -1 characteristics for amino groups whereas the 1 H NMR spectrum exhibited singlet signal at 6.64 ppm characteristics for NH2 group.Finally, the structure of Munich product 9 was proved by the spectral analysis, where its 1 H NMR spectrum showed two singlet signals at 4.22 and 4.56 ppm characteristics for 2 CH2 groups.

Conclusion
In the present work, we introduced a synthetic route for the synthesis of some new heterocyclic compounds containing thiazolopyrimidine moiety.Since, the compound 4-oxo-6-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (1) was prepared according to the reported procedure and used as a precursor for synthesizing the target compounds.In addition, all the synthesized compounds were characterized using spectroscopic data and elemental analyses.

Materials and methods
All melting points are uncorrected and measured on a Fisher-John apparatus.Elemental analysis was determined on an elementar analysensysteme GmbH -vario EL III elemental analyzer in the central lab of Assiut University.Their results were found to be in good agreement (±0.2%) with the calculated values.IR spectra were recorded on a Pye-Unicam Sp-100 spectrophotometer using KBr wafer technique. 1H NMR spectra were obtained on BRUKER 400 MHz spectrometers in a suitable deuterated solvent using tetramethylsilane as an internal standard (chemical shifts in ppm), otherwise stated.Mass spectra were obtained on JEOL JMS-600 apparatus.Preparative and analytical TLC were carried out on silica gel plates (Fluka 70643-50EA.SIGMA-ALDRICH, Germany) using UV light All reactions were carried out under an air atmosphere.4-oxo-6-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5carbonitrile (1) was prepared according to the reported procedure. 52
A mixture of chloroacetamide derivative 7 (0.5 g, 0.99 mmol) and aniline (2 mmol) was dissolved in 20 mL ethanol and refluxed for 3 h.The solid precipitate, which was formed, filtered off, dried and recrystallized from ethanol-water (2:1) to give pale brown needles in 46% yield; m.