Application of α-bromotoluene-D7_Kain Industrial Additive

Overview^[1]

Alpha-bromotoluene-D7 is an isotope-labeled compound that can be prepared from toluene-d8 by one-step bromination and can be used as a drug synthesis intermediate.

Preparation^[2]

Add toluene-d8 (1.0 mL, 10 mmol), NBS (12 mmol, 2.2 g), CCl₄ (30 mL) into a catalytic amount of tert-butyl peroxybenzoate (30 mol%, 580 μL) into a 50 mL round-bottomed flask equipped with a magnetic stirring bar. The reaction was monitored by TLC.

Apply^{[1] [3]}

WO2018229683 reported that α-bromotoluene-D7 can be used to prepare 2,5-dimethyl-6-(4- ((phenyl-d5)methoxy-d2)piperidin-1-yl)-[1,2,4] triazolo[1,5-a]pyrimidin-7(4H)-one. The compound has inhibitory and anti-parasitic activity against kinetosome protozoa. Inhibits motile plastid parasite cell growth by inhibiting the parasitic proteasome and may be used as a therapy for leishmaniasis and Chagas disease.

WO2018041122 reported that A-bromotoluene-D7 can be used to prepare the following three compounds.

These three compounds are new small molecule FXIa antagonists. The compounds exhibit excellent anticoagulant effects on human blood and have good pharmacokinetic activity. They can be used to effectively treat and/or prevent cardiovascular and cerebrovascular diseases. Disease and thrombosis symptoms. The coagulation cascade is initiated by the intrinsic pathway (also known as the contact-activated pathway) and the exogenous pathway (also known as the tissue factor pathway) to generate FXa, which then generates thrombin (FIIa) through the common pathway, and finally forms fibrin. The intrinsic pathway refers to the process in which factor XII is activated to form the XIa-VIIIa-Ca2±P L complex and activates factor and activates the process of factor X. The common pathway refers to the process in which the two pathways merge into one after the formation of factor play a key role. In the coagulation cascade reaction, thrombin can feedback activate FXI, and the activated FXI (FXIa) in turn promotes the large production of thrombin, thus amplifying the coagulation cascade reaction. Therefore, FXI antagonists have been widely developed for the treatment of various thrombus.

Main reference materials

[1] (WO2018229683) 5,6-FUSED-BICYCLIC COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES

[2]Jaiswal Y , Kumar Y , Kumar A . Palladium-Catalyzed Regioselective C-H Alkenylation of Arylacetamides via Distal Weakly Coordinating Primary Amide as Directing Group[J]. The Journal of Organic Chemistry, 2017:acs .joc.7b02618.

[3] (WO2018041122) Oxopyridine amide derivatives, their preparation methods and their applications in medicine