1297537-35-9

Basic information

• Product Name: 2-Chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile
• Synonyms: 2-Chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile
• CAS NO: 1297537-35-9
• Molecular Weight: 287.749
• Mol File: 1297537-35-9.mol
• Article Data: 12

Chemical Properties

• Boiling Point: 490.7±45.0 °C(Predicted)
• Density: 1.32±0.1 g/cm3(Predicted)
• CAS DataBase Reference: 2-Chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile(1297537-35-9)
• EPA Substance Registry System: 2-Chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile(1297537-35-9)

Safety Data

• Hazardous Substances Data: 1297537-35-9(Hazardous Substances Data)

Upstream product

• 154607-01-9 4-bromo-2-chlorobenzonitrile 
• 1105511-68-9 [1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl]boronic acid 
• 548797-51-9 2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile 
• 449758-17-2 1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole 
• 903550-26-5 1-tetrahydropyran-1H-pyrazolylboronic ester 

Downstream Products

• 1297537-39-3 2-Chloro-4-(1H-pyrazol-3-yl)benzonitrile hydrochloride 
• 1297537-37-1 2-chloro-4- (1H-pyrazol-3-yl)benzonitrile 
• 1297537-33-7 5-acetyl-N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1H-pyrazole-3-carboxamide 
• 1297538-32-9 N-{(2S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-5-[(1RS)-1-hydroxyethyl]-1H-pyrazole-3-carboxamide 
• 1297542-94-9 (S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-((2,5-dioxopyrrolidin-1-yl)methyl)oxazole-4-carboxamide 
• 1297542-60-9 (S)-2-(3-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-ylcarbamoyl)isoxazol-5-yl)propan-2-yl acetate 
• 1297542-18-7 (S)-2-((1H-imidazol-1-yl)methyl)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)oxazole-4-carboxamide 
• 1297542-22-3 (S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(chloromethyl)oxazole-4-carboxamide 
• 1297540-19-2 (S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1,2,5-oxadiazole-3-carboxamide 
• 1297540-14-7 (S)-4-(1-(2-aminobutyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile 
• 1297540-05-6 1-(5-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-ylcarbamoyl)-1H-pyrazol-3-yl)ethyl 2-(dimethylamino)acetate 
• 1297539-13-9 (S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(2-hydroxypropan-2-yl)isoxazole-3-carboxamide 
• 1297538-32-9 N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-3-(1-hydroxyethyl)-1H-pyrazole-5-carboxamide 
• 1297537-95-1 (S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)isoxazole-3-carboxamide 

Relevant articles and documents

SUBSTITUTED PYRAZOLE COMPOUNDS, COMPOSITIONS CONTAINING SAME, AND USE THEREOF

The present invention provides substituted pyrazole compounds, compositions containing same, and use thereof. The substituted pyrazole compounds comprise a compound represented by formula (I) or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate, or solvate thereof. The compound represented by formula (I) can serve as a tissue selective androgen receptor modulator (SARM), particularly serving as a drug for treating prostate cancer and other AR-dependent conditions and diseases in which AR antagonism is desired.

Metabolism and mass balance of the novel nonsteroidal androgen receptor inhibitor darolutamide in humans

The biotransformation and excretion of darolutamide were investigated in a phase I study. Six healthy male volunteers received a single dose of 300 mg 14C-darolutamide as an oral solution in the fasted state. Plasma, urine, and feces samples were analyzed for mass balance evaluation by liquid scintillation counting (LSC). Metabolite profiling and identification were determined using liquid chromatography mass-spectrometry with off-line radioactivity detection using LSC. Complete mass balance was achieved, with mean radioactivity recovery of 95.9% within 168 hours (63.4% in urine, 32.4% in feces). The administered 1:1 ratio of (S,R)- and (S,S)darolutamide changed to approximately 1:5, respectively, in plasma. Darolutamide and the oxidation product, keto-darolutamide, were the only components quantifiable by LSC in plasma, accounting for 87.4% of total radioactivity, with a 2.1-fold higher plasma exposure for keto-darolutamide. Aside from darolutamide, the most prominent metabolites in urine were O-glucoronide (M-7a/b) and N-glucuronide (M-15a/b), as well as pyrazole sulfates (M-29, M-24) and glucuronides (M-21, M-22) resulting from oxidative cleavage of the parent. The darolutamide diastereomers were mainly detected in feces. In vitro assays showed that darolutamide metabolism involves a complex interplay between oxidation and reduction, as well as glucuronidation. Interconversion of the diastereomers involves oxidation to keto-darolutamide, primarily mediated by CYP3A4, followed by reduction predominantly catalyzed by cytosolic reductase(s), with aldo-keto reductase 1C3 playing the major role. The latter reaction showed stereoselectivity with preferential formation of (S,S)-darolutamide.

Method for preparing antitumor drug darolutamide

The invention relates to a method for preparing an antitumor drug darolutamide. A one-step Suzuki reaction is carried out, and then deprotection, hydroxylamine condensation and amide condensation reactions are carried out to obtain the darolutamide. The method has the advantages of few reaction steps, high reaction yield of each step, and simplicity in operation, so the total yield of the whole route is high, and the method has good experiment operationality.