143782-23-4

Basic information

• Product Name: 3-Fluoro-4-methylphenylisothiocyanate
• Synonyms: 4-isothiocyanato-2-(trifluoroMethyl)benzonitrile;Benzonitrile,4-isothiocyanato-2-(trifluoroMethyl)-;3. 4-Isothiocyanato-2-(trifluoroMethyl)benzonitrile;4-cyano-3-trifluoromenthylphenylisothiocyanate;4-Isothiocyanato-2-(trifluoromethyl)benzonitrile,Enzalutamide intermediate;4-isothiocyananto-2-(trifluoromethyl) benzonitrile;Isothiocyanato-2-(trifluoromethyl)benzonitrile
• CAS NO: 143782-23-4
• Molecular Formula: C₉H₃F₃N₂S
• Molecular Weight: 228.194
• EINECS: 1592732-453-0
• Mol File: 143782-23-4.mol
• Article Data: 47

Chemical Properties

• Melting Point: 39.0 to 43.0 °C
• Boiling Point: 331℃
• Flash Point: 154℃
• Appearance: /
• Density: 1.31
• CAS DataBase Reference: 3-Fluoro-4-methylphenylisothiocyanate(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Fluoro-4-methylphenylisothiocyanate(143782-23-4)
• EPA Substance Registry System: 3-Fluoro-4-methylphenylisothiocyanate(143782-23-4)

Safety Data

• Hazardous Substances Data: 143782-23-4(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 143782-23-4 differently. You can refer to the following data:
1. 4-Isothiocyanoyl-2-(trifluoromethyl)benzonitrile is a reagent used to synthesize thioimidazolinone compounds and is a potential anti-prostate cancer drug. It is also used as an intermediate of enzalutamide.
2. 4-Cyano-3-trifluoromethylphenylisothiocyanate is an reagent used in the synthesis of thioxoimidazolidinones as potential anti-prostate cancer agents.

Synthesis

4-Amino-2-trifluoromethylbenzonitrile, (2.23 g, 12 mmol) was added portionwise over15 minutes into the well-stirred heterogeneous mixture of thiophosgene (1 ml, 13 mmol) in water (22 ml) at room temperature. Stirring was continued for an additional 1 h. The reaction medium was extracted with chloroform (3 x 15 ml). The combined organic phase was dried over MgSO4 and evaporated to dryness under reduced pressure to yield desired product, 4-isothiocyanato-2-trifluoromethylbenzonitrile, (Ia), as brownish solid and was used as such for the next step (2.72 g, 11.9 mmol, 99%).

Upstream product

• 654-70-6 4-amino-2-trifluoromethylbenzonitrile 
• 6160-65-2 1,1'-Thiocarbonyldiimidazole 
• 463-71-8 thiophosgene 

Downstream Products

• 1398045-91-4 4-(3-{3-fluoro-4-[4-(3-hydroxy-azetidin-1-yl)-4-oxo-butyl]-phenyl}-4,4-dimethyl-5-oxo-2-thioxo-imidazolidin-1-yl)-2-trifluoromethyl-benzonitrile 
• 1398045-99-2 4-(3-{3-fluoro-4-[4-(4-hydroxy-piperidin-1-yl)-4-oxo-butyl]-phenyl}-4,4-dimethyl-5-oxo-2-thioxo-imidazolidin-1-yl)-2-trifluoromethyl-benzonitrile 
• 1398046-03-1 4-(3-{3-fluoro-4-[4-(4-methyl-piperazin-1-yl)-4-oxo-butyl]-phenyl}-4,4-dimethyl-5-oxo-2-thioxo-imidazolidin-1-yl)-2-trifluoromethyl-benzonitrile 
• 1398046-23-5 4-{4,4-dimethyl-3-[6-(3-oxazol-2-yl-propyl)-pyridin-3-yl]-5-oxo-2-thioxo-imidazolidin-1-yl}-2-trifluoromethyl-benzonitrile 
• 915087-33-1 enzalutamide 
• 1351185-35-7 N-methyl-4-{(R)-5-methyl-4-oxo-2-thioxo-3-[3-(trifluoromethyl)-4-cyanophenyl]imidazolidin-1-yl}-2-fluorobenzamide 
• 1351185-34-6 N-methyl-4-{(S)-5-methyl-4-oxo-2-thioxo-3-[3-(trifluoromethyl)-4-cyanophenyl]imidazolidin-1-yl}-2-fluorobenzamide 

Relevant articles and documents

Spirocyclic Thiohydantoin Antagonists of F877L and Wild-Type Androgen Receptor for Castration-Resistant Prostate Cancer

Androgen receptor (AR) transcriptional reactivation plays a key role in the development and progression of lethal castration-resistant prostate cancer (CRPC). Recurrent alterations in the AR enable persistent AR pathway signaling and drive resistance to the treatment of second-generation antiandrogens. AR F877L, a point mutation in the ligand binding domain of the AR, was identified in patients who acquired resistance to enzalutamide or apalutamide. In parallel to our previous structure-activity relationship (SAR) studies of compound 4 (JNJ-pan-AR) and clinical stage compound 5 (JNJ-63576253), we discovered additional AR antagonists that provide opportunities for future development. Here we report a highly potent series of spirocyclic thiohydantoins as AR antagonists for the treatment of the F877L mutant and wild-type CRPC.

Exploring the tetrahydroisoquinoline thiohydantoin scaffold blockade the androgen receptor as potent anti-prostate cancer agents

Prostate cancer (PC) is a major cause of cancer-related male death in worldwide and the identification of new and improved potent anti-PC molecules is constantly required. A novel scaffold of tetrahydroisoquinoline thiohydantoin was rationally designed based on the enzalutamide structures and our pre-work, leading to the discovery of a series of new antiproliferative compounds. Several new analogues displayed improved androgen receptor (AR) antagonistic activity, while maintaining the higher selective toxicity toward LNCaP cells (AR-rich) versus DU145 cells (AR-deficient) compared to enzalutamide. In fact, compound 55 exhibited promising in vitro antitumor activity by impairing AR unclear translocation. More importantly, 55 showed better pharmacokinetic properties compared to the compound 1 reported in our pre-work. These results demonstrate a step towards the development of novel and improved AR antagonists.

ARYL HYDANTOIN HETEROCYCLES AND METHODS OF USE

Disclosed is a compound of formula (I) in which R1, R2, R3, X1, X2, X2', X3, X4, ring A, m, n, and o are as described herein. The compound of formula (I) is useful for treating a disorder associated with androgen receptor malfunction, such as a hyperproliferative disorder, in a subject in need thereof.

Synthesis method of 4-isothiocyanato-2-(trifluoromethyl)benzonitrile

The invention discloses a synthesis method of 4-isothiocyanato-2-(trifluoromethyl)benzonitrile. The synthesis method comprises the following steps: with 3-trifluoromethyl-4-cyanobenzoic acid as an initial raw material, firstly, subjecting 3-trifluoromethyl-4-cyanobenzoic acid to reacting with diphenyl azidophosphate under an anhydrous condition to generate 4-isocyanato-2-(trifluoromethyl)benzonitrile, and then subjecting 4-isocyanato-2-(trifluoromethyl)benzonitrile to reacting with a Lawson reagent to obtain the compound 4-isothiocyanato-2-(trifluoromethyl)benzonitrile. The method has the advantages of simple synthetic route, one-pot reaction, mild reaction conditions, simple post-treatment, high product yield (wherein total yield is greater than or equal to 83.9%), and easy industrial production.