4-Aminopyrazolo[3,4-d]pyrimidine

Description

4-aminopyrazolo[3,4-d]pyrimidine (4-APP), the isomer of adenine with the five-membered ring in the pyrazole configuration, is by far the most potent inhibitor of both enzymatic reactions catalyzed by Stx1. It is also a new type of mTOR inhibitor. The 4-aminopyrazolo[3,4-d]pyrimidines, a well-characterized class of compounds for tyrosine kinase inhibition, were used as a Src inhibitor module that blocks the adenosine binding site[1-2].

Chemical Properties

Light Tan Solid

Uses

4-Amino-1H-pyrazolo[3,4-d]pyrimidine decreases serum cholesterol markedly in rats.

Hazard

4-Aminopyrazolo[3,4-d]pyrimidine is harmful, irritating to the eyes and skin, and may cause respiratory irritation by inhalation. It is toxic if swallowed.

Synthesis

4-Chloro-1H-pyrazolo[3,4-d]pyrimidine (200 mg, 1.29 mmol) was used as starting material and dissolved in tetrahydrofuran (THF, 2.0 mL). Subsequently, ammonium hydroxide (2.0 mL) was added to this solution. The reaction mixture was stirred at 20 to 30 °C for 2 hours. After the reaction was completed, the mixture was concentrated. The concentrate was ground with acetonitrile (MeCN, 0.5 mL) and the product was subsequently collected by filtration to afford 4-aminopyrazolo[3,4-d]pyrimidine (37) as a red solid (100 mg, 57% yield).

References

[1] M Brigotti. “4-Aminopyrazolo[3,4-d]pyrimidine (4-APP) as a novel inhibitor of the RNA and DNA depurination induced by Shiga toxin 1.” Nucleic Acids Research 28 12 (2000): 2383–8.
[2] Ho Jin Lee. “Development of a 4-aminopyrazolo[3,4-d]pyrimidine-based dual IGF1R/Src inhibitor as a novel anticancer agent with minimal toxicity.” Molecular Cancer 17 1 (2018): 50.