Application of 4-bromophenyl isothiocyanate_Kain Industrial Additive

Background and Overview

4-Bromophenyl isothiocyanate is a carboxylic acid ester organic compound that can be used as a pharmaceutical intermediate.

Preparation^[1]

The preparation method is as follows. By replacing p-chloroaniline with p-bromoaniline, 4-bromophenyl isothiocyanate can be prepared. Weigh thiocarbonyldiimidazole (300 mg, 1.69 mmol) into the reaction bottle, add 10 mL of dry THF, dissolve p-chloroaniline (235 mg, 1.85 mmol) in 2 mL of dry DCM and slowly add it dropwise to the reaction bottle, and react at room temperature for 2 hours. , purified by column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain the intermediate phenyl chloroisothiocyanate (145 mg, 0.86 mmol),

Apply ^[1]

In recent years, invasive fungal infections have continued to increase, especially in patients with HIV, tumors, organ transplants, hematology diseases, and intensive care patients. The morbidity and mortality of invasive fungal infections have continued to increase. Candida albicans, Cryptococcus neoformans and Aspergillus fumigates are currently the three major pathogenic fungi with the highest morbidity and mortality.

Currently, there are only four types of drugs used clinically to treat deep fungal infections: polyenes (amphotericin B), nucleic acids (5-fluorocytosine), and azoles (fluconazole, itraconazole, etc. ). Although the above-mentioned drugs have made great progress in the prevention and treatment of fungal infections, there are still great difficulties in the treatment of deep fungal infections, especially refractory fungal diseases (such as cryptococcal meningitis).

Amphotericin B is still one of the first-choice drugs for cryptococcosis in the central nervous system, but it has serious side effects; 5-fluorocytosine is very easy to develop resistance when used alone, and is often used in combination with amphotericin B, and It causes damage to the liver, kidneys, and hematopoietic system; although fluconazole has mild side effects, its efficacy when used alone to treat cryptococcal meningitis is not ideal, and drug resistance is becoming increasingly serious, further reducing the efficacy; itraconazole is a pharmacological agent It has poor kinetic properties and is often used in combination with amphotericin B or as maintenance therapy; while echinocandin antifungal drugs are ineffective against cryptococci. Therefore, it is very important to develop new structural types, mechanisms of action and anti-drug resistance to deep fungal infections. CN201810466614.7 provides a new class of antifungal small molecule inhibitors. The antifungal small molecule inhibitor is a pyrazolone amide antifungal compound or a pharmaceutically acceptable salt thereof. The structure of the compound is shown in General Formula I:

Wherein, Lower hydroxyalkyl group, lower alkoxy group, lower alkylamino group, lower haloalkoxy group, lower haloalkylamino group, lower cycloalkylamino group, lower alkynylamino group, amide group, lower cycloalkylamido group, lower amide group Alkyl, benzyl, substituted benzyl, nitro, ethynyl, morpholinyl, substituted piperazinyl or nitrile group; R2 is hydrogen, substituted or unsubstituted aromatic ring, aliphatic ring, or lower acyl group; R3 and R4 One is amino and the other is carbonyl oxygen. 4-Bromophenyl isothiocyanate can be used to prepare compound 6C, the route is as follows:

Main reference materials

[1] CN201810466614.7 Pyrazolone amide antifungal drugs and their preparation methods and applications