Background and overview[1]
P-Bromophenyl acetonitrile is a nitrile compound. Nitriles are a class of organic compounds containing cyano groups (-CN) and are important organic synthesis intermediates. Since the cyano group has high reactivity, the corresponding amine compounds can be produced through hydrogenation reaction. They are important raw materials for manufacturing medicines, pesticides, dyes, spices, surfactants, etc., and are widely used in various fields of the national economy. .
Preparation[1]
A suspension of 4-bromobenzyl bromide (5.00 g, 0.020 mol) and sodium cyanide (1.18 g, 0.024 mol, 1.2 equiv) in DMF-water (9:1, 35 ml) was incubated at 40° C for 12 hours. The reaction mixture was quenched with water and extracted with EtOAc. The combined organic matter was washed with NaCl (sat) and dried with Na2SO4. The solvent was removed under reduced pressure to give 3.9 g (89%) of the desired product.
Apply[2]
P-Bromophenyl acetonitrile can be used to prepare compounds with the following structure, which is a PRMT5 inhibitor. Loss of the enzyme methylthioadenosine phosphorylase (MTAP) confers selective dependence on PRMT5 and its binding partner WDR77. MTAP is often lost due to its proximity to the often deleted tumor suppressor gene CDKN2A. Cells carrying a deletion of MTAP have increased intracellular concentrations of methylthioadenosine (MTA, a metabolite of MTAP cleavage). Furthermore, MTA specifically inhibits PRMT5 enzyme activity. Administration of MTA or small molecule PRMT5 inhibitors showed preferential impairment of cell viability in MTAP-free cancer cell lines compared with their isogenic MTAP-expressing counterparts. PRMT5 has been revealed to be potentially vulnerable in multiple cancer lineages enhanced by common ‘passenger’ genomic alterations.
References
[1] [Chinese invention, Chinese invention authorization] CN201410522472.3 Manufacturing method of nitrile and its corresponding amine
[2] [Invented in China] CN201910297684.9 Inhibitors of protein arginine methyltransferase 5 (PRMT5), pharmaceutical products and methods thereof
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