2-Amino-5-(4-methoxyphenyl)-1,3,4-thiadiazole

Uses

2-Amino-5-(4-methoxyphenyl)-1,3,4-thiadiazole is a thiadiazole derivative that is potent and selective human adenosine A3 receptor antagonist. It is also used as a reactant in the synthesis of substituted thiadiazolyl(styryl)quinazolinones with anticonvulsant, sedative-hypnotic, and CNS depressant activities.

Synthesis Reference(s)

Journal of the American Chemical Society, 73, p. 906, 1951 DOI: 10.1021/ja01147a007

Synthesis

5.1.1 Synthesis of 5-(4-methoxyphenyl)-1,3,4-thiadiazol-2-amine (61): p-Methoxybenzoic acid (5.18 g, 25 mmol) and aminothiourea (2.28 g, 25 mmol) were dissolved in POCl3 (7 mL) and stirred vigorously for 0.5 hours at 75°C. After the reaction was completed, H2O (30 mL) was added and the reaction mixture was heated to reflux for 4 hours. Subsequently, the pH of the reaction mixture was adjusted with 50% NaOH solution to 8. The precipitate was collected by filtration and the filter cake was recrystallized with ethanol to afford yellow crystals of the target compound 61 in 82% yield with a melting point of 219-220 °C (EtOH).ESI-MS m/z: 208.2 [M + H]+; 1H NMR (DMSO-d6) δ 3.80 (s, 3H ), 7.01-7.03 (m, 2H), 7.23 (s, 2H), 7.67-7.69 (m, 2H). Compounds 60-81 were synthesized in the same way.

References

[1] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 14, p. 6663 - 6668
[2] Tetrahedron, 2018, vol. 74, # 31, p. 4161 - 4167
[3] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 21, p. 5766 - 5775
[4] Medicinal Chemistry, 2014, vol. 10, # 4, p. 376 - 381
[5] Medicinal Chemistry Research, 2012, vol. 21, # 6, p. 816 - 824