2-Amino-5-bromo-[1,3,4]thiadiazole

Chemical Properties

Yellow powder

Uses

2-Amino-5-bromo-1,3,4-thiadiazole can be used:

• As the key building block for the synthesis of myriad of thiadiazolo[3,2-α]pyrimidin-7-ones which have diverse biological activities.
• For the synthesis of 2-bromoimidazo[2,1-b][1,3,4]thiadiazoles by reacting with α-bromo ketones.

Synthesis

General procedure for the synthesis of 2-amino-5-bromo-1,3,4-thiadiazole from 2-amino-1,3,4-thiadiazole: 1. A solution of 2-amino-1,3,4-thiadiazole (5 g, 48.45 mmol) in methanol (70 mL) was added to a reaction flask. 2. Sodium bicarbonate (8.14 g, 96.90 mmol) and bromine (2.5 mL, 48.45 mmol) were added sequentially. 3. The reaction mixture was stirred at room temperature until the complete disappearance of the ingredients was demonstrated by thin layer chromatography (TLC) monitoring (about 30-40 minutes). 4. After completion of the reaction, the solvent was removed by rotary evaporator under reduced pressure. 5. The crude product was ground with a solvent mixture of methanol-ether (1:1, v/v) to give 2-amino-5-bromo-[1,3,4]thiadiazole as a white solid. 6. The mother liquor containing a small amount of product was purified by fast column chromatography using dichloromethane-methanol (99:1, v/v) as eluent. 7. The product was confirmed by nuclear magnetic resonance hydrogen spectroscopy (1H NMR, 300 MHz, DMSO-d6): δ 7.52 (br s, 2H). 8. Mass spectrometry (ES+) analysis showed m/z 181 ([M+H]+, calculated value: 180.0). Yield: 99%.

References

[1] Patent: WO2009/40552, 2009, A2. Location in patent: Page/Page column 50-51
[2] ACS Medicinal Chemistry Letters, 2012, vol. 3, # 3, p. 198 - 202
[3] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5305 - 5309
[4] European Journal of Medicinal Chemistry, 2018, vol. 155, p. 34 - 48
[5] Patent: WO2013/163244, 2013, A1. Location in patent: Paragraph 00179; 00180