Preparation and application background and overview of 3-bromo-5-fluoro-2-methylpyridine
3-Bromo-5-fluoro-2-methylpyridine is an organic intermediate that can be prepared from 2,3-dibromo-5-fluoropyridine and methylboronic acid through a one-step reaction. There are reports in the literature that it can be used to prepare WDR5 inhibitors.
Preparation and application of 3-bromo-5-fluoro-2-methylpyridine
Preparation of 3-bromo-5-fluoro-2-methylpyridine: 2,3-dibromo-5-fluoropyridine (5.0g, 19.6 mmol), Pd(PPh3)4 (1.13g, 0.98mmol) ) and methylboronic acid (3.52 g, 58.9 mmol) were combined in dioxane (50 mL) and treated with K2CO3 (8.13, 58.9 mmol) and water (10 mL). The mixture was purged with N2 and heated to 110°C in a sealed container for 16 hours. The cooled mixture was partitioned between water (100 mL) and EtOAc (50 mL) and the layers were separated. The aqueous layer was extracted with EtOAc (2 x 50 mL) and the combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography, eluting with 1-3% EtOAc/hexanes, to afford the product as a white solid (1.20 g, 32% yield). Polycarbonate diol MS (apci) m/z = 190.2 (M+).
Preparation and application of 3-bromo-5-fluoro-2-methylpyridine
3-Bromo-5-fluoro-2-methylpyridine can be used to prepare WDR5 inhibitors with the following structure. The WDR5 protein also involves diphenylboronic acid in other biological processes. For example, in human lung cancer cells A549, WDR5 protein can regulate the expression of genes related to the p53 signaling pathway. WDR5 can also activate the transcription of self-renewal genes, causing embryonic stem cells to self-renew. The interaction between WDR5 and MYC drives tumorigenesis. In breast cancer cells, WDR5 regulates Notch gene expression. Under hypoxia induction, WDR5 can also cooperate with HADC3 to activate mesenchymal gene expression.
References
[1] From PCT Int. Appl., 2011006074, 13 Jan 2011
[2] From PCT Int. Appl., 2020086857, 30 Apr 2020
