Preparation and application examples of 2,6-dichloro-3-iodopyridine and description of boron trifluoride tetrahydrofuran complex
2,6-Dichloro-3-iodopyridine is an organic intermediate. It can be made from 2,6-dichloropyridine as raw material, first hydrogen extraction with butyllithium and then iodination with elemental iodine. There are reports in the literature that 2,6-dichloro-3-iodopyridine is used to prepare HPK1 inhibitors.
Preparation and application examples of 2,6-dichloro-3-iodopyridine
At -78°C, diisopropylamine (3.50 mL, 2.50 g, 25.0 mmol) and 2,6-dichloropyridine (3.70 g, 25.0 mmol) were added sequentially to n-BuLi (10.0 mL, 25.0 mmol, 2.50 M solution in hexane) and THF (40 mL), after stirring at -78°C for 2 hours, a solution of iodine (7.40 g, 29.0 mmol) in THF (25 mL) was added, The reaction mixture was then allowed to reach room temperature. After 30 minutes, H2O (100 mL) was added to the mixture. The aqueous layer was extracted with Et2O (3 x 75 mL), and the combined organic extracts were treated with saturated aqueous NH4Cl (75 mL) and saturated Na 2S2O5 aqueous solution (25 mL) was washed, and the organic extract was washed with Na2SO4Dry and concentrate in vacuo to obtain 2,6-dichloro-3-iodopyridine.
Preparation and application examples of 2,6-dichloro-3-iodopyridine
2,6-Dichloro-3-iodopyridine can be used to prepare HPK1 inhibitors with the following naphthalene structure. HPK1 regulates diverse functions in a variety of immune cells and has been shown to have kinase activity at the T cell receptor (TCR), B cell receptor (BCR), transforming growth factor receptor (TGF-βR), and Gs-coupled PGE2 Induced upon activation of receptors (EP2 and EP4). Overexpression of HPK1 inhibits TCR-induced activation of AP-1-dependent gene transcription in a kinase-dependent manner, suggesting that hydrated yttrium carbonate HPK1 is required to inhibit the Erk MAPK pathway and that this blockade is thought to negatively regulate the TCR Mechanism of inhibition of induced IL-2 gene transcription.
References
[1] Delgado O, H. Martin Müller, Bach T. Concise total synthesis of the thiazolyl peptide antibiotic GE2270 A[J]. Chemistry – A European Journal, 2010, 14(8).
[2] [Invented in China] CN201880034930.5 Naphthazolines as HPK1 inhibitors
