3-Iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Description

3-Iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine is a key intermediate in the synthesis of ibrutinib.

Uses

3-Iodo-3H-pyrazolo[3,4-d]pyrimidin-4-amine acts as a reagent in the discovery and preparation of CHMFL-FLT3-122 as potent and orally available FLT3 kinase inhibitor for FLT3-ITD positive acute myeloid leukemia. Development and preparation of potent and selective Plasmodium falciparum calcium-dependent protein kinase 4 (PfCDPK4) inhibitors that block the transmission of malaria to mosquitoes.

Synthesis

A solution of 3H-pyrazolo[3,4-d]pyrimidin-4-amine (10 g, 0.074 mol) and n-iodo-succinamide (25 g, 0.111 mol) in DMF (80 mL) was heated to 80° C. overnight under an argon atmosphere. The resulting solid was filtered and rinsed with cold EtOH. The product was dried in vacuo overnight to yield 3-Iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (24 g, 100 per cent yield).

References

[1] Patent: US2007/293516, 2007, A1. Location in patent: Page/Page column 12; 16
[2] Angewandte Chemie - International Edition, 2016, vol. 55, # 36, p. 10909 - 10912
[3] Angew. Chem., 2016, vol. 128, p. 11069 - 11073,5
[4] Journal of Medicinal Chemistry, 2017, vol. 60, # 18, p. 7725 - 7744
[5] Patent: US2012/202785, 2012, A1. Location in patent: Page/Page column 258