1146629-83-5

Usage

Uses

Used in Pharmaceutical Development:
(R)-3-(4-bromo-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile is used as a key intermediate in the synthesis of pharmaceuticals for its unique structural features and potential biological activities. Its presence in drug molecules can contribute to the modulation of specific biological targets, leading to the development of new therapeutic agents.
Used in Agrochemical Development:
In the agrochemical industry, (R)-3-(4-bromo-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile is used as a building block for the creation of novel agrochemicals. Its unique chemical properties can be harnessed to develop compounds with specific pesticidal or herbicidal activities, enhancing crop protection and yield.
Used as a Reagent in Chemical Reactions:
(R)-3-(4-bromo-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile is utilized as a reagent in various chemical reactions, particularly in organic synthesis. Its bromine atom and nitrile group can participate in a range of reactions, such as nucleophilic substitution, addition reactions, and cycloadditions, facilitating the synthesis of complex organic molecules for research and industrial applications.
Used in Medicinal Chemistry Research:
In the field of medicinal chemistry, (R)-3-(4-bromo-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile is employed as a research tool to explore the structure-activity relationships of potential drug candidates. Its unique chemical properties allow for the investigation of its interactions with biological targets, providing insights into the design of more effective therapeutic agents.

Upstream product

• 1146629-82-4 (3R)-3-(4-bromo-1H-pyrazol-1-yl)-3-cyclopentylpropanal 
• 4630-80-2 methyl cyclopentane carboxylate 
• 2075-45-8 4-bromo-1H-pyrazole 
• 95882-33-0 3-cyclopentyl-3-oxopropanenitrile 
• 136823-41-1 methyl 3-cyclopentylacrylate 
• 872-53-7 cyclopentanealdehyde 
• 137-43-9 Cyclopentyl bromide 
• 54125-23-4 cyclopentylallene 

Downstream Products

• 1146629-84-6 (3R)-3-cyclopentyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propanenitrile 
• 941678-49-5 ruxolitinib 

Relevant academic research and scientific papers

Structural Insights into JAK2 Inhibition by Ruxolitinib, Fedratinib, and Derivatives Thereof

The discovery that aberrant activity of Janus kinase 2 (JAK2) is a driver of myeloproliferative neoplasms (MPNs) has led to significant efforts to develop small molecule inhibitors for this patient population. Ruxolitinib and fedratinib have been approved for use in MPN patients, while baricitinib, an achiral analogue of ruxolitinib, has been approved for rheumatoid arthritis. However, structural information on the interaction of these therapeutics with JAK2 remains unknown. Here, we describe a new methodology for the large-scale production of JAK2 from mammalian cells, which enabled us to determine the first crystal structures of JAK2 bound to these drugs and derivatives thereof. Along with biochemical and cellular data, the results provide a comprehensive view of the shape complementarity required for chiral and achiral inhibitors to achieve highest activity, which may facilitate the development of more effective JAK2 inhibitors as therapeutics.

Preparation method of ruxolitinib intermediate (3R)-3-(4-Br-1H-pyrazole-1-yl)-cyclopentyl propanenitrile

The present invention relates to a preparation method of ruxolitinib intermediate (3R)-3-(4-Br-1H-pyrazole-1-yl)-cyclopentyl propanenitrile, and the method comprises the following steps: (1) synthesisof 3-oxo-3-cyclopentyl propionitrile (II); (2) synthesis of (S)-3-cyclopentyl-3-hydroxypropionitrile (III); (3) synthesis of (3R)-3-(4-nitro-1H-pyrazole-1-yl)-cyclopentyl propionitrile (IV); (4) synthesis of (3R)-3-(4-amino-1H-pyrazole-1-yl)-cyclopentyl propionitrile (V); and (5) (3R)-3-(4-Br-1H-pyrazole-1-yl)-cyclopentyl propanenitrile (VI). The method has the advantages of good stereoselectivity, low cost, mild reaction conditions, no requirement on harsh reaction such as high temperature, high pressure and ultra-low temperature.

Intermediate of JAK inhibitor, and preparation method thereof

The present invention relates to a novel key intermediate of a JAK inhibitor ruxolitinib, and a preparation method thereof, wherein the chemical name of the intermediate is (R)-3-(4-boric acid-1H-pyrazole-1-yl)-3-cyclopentylpropionitrile. According to the present invention, the new ruxolitinib preparation route is provided, wherein each reaction of the route has the high yield, the total yield ofthe route is high, the purity of the obtained product is good, the post-treatment of the reaction is simple, and column chromatography is not required; by adopting the route, the required raw materials or catalysts and other materials are relatively easy to obtain; and compared to the method in the prior art, the method of the present invention is economical and is suitable for industrial production.

Preparation methods of JAK inhibitor and salt thereof

The present invention relates to preparation methods of a JAK inhibitor and a salt thereof. The preparation method comprises: (1) carrying out a Suzuki coupling reaction on (R)-3-(4-boronic acid-1H-pyrazol-1-yl)-3-cyclopentylpropionitrile and 6-halogen-5-(2-methoxyvinyl)pyrimidin-4-ylamine to generate (3R)-cyclopentyl-3-[4-(5-(2-methoxyvinyl)pyrimidin-4-ylamine)pyrazol-1-yl]propionitrile; and (2)carrying out a protection group removing and ring-closure reaction on the (3R)-cyclopentyl-3-[4-(5-(2-methoxyvinyl)pyrimidin-4-ylamine)pyrazol-1-yl]propionitrile to generate a JAK inhibitor ruxolitinib. According to the present invention, the new ruxolitinib preparation route is provided, wherein each reaction of the route has the high yield, the total yield of the route is high, the purity of theobtained product is good, the post-treatment of the reaction is simple, and column chromatography is not required; by adopting the route, the required raw materials or catalysts and other materials are relatively easy to obtain; and compared to the method in the prior art, the method of the present invention is economical and is suitable for industrial production.

A Russo advantage for Nepal synthesis of intermediates method (by machine translation)

The invention relates to a Russo advantage for Nepal synthesis of intermediates method, first of all by the cyclopentane carboxylic acid methyl ester and acetonitrile catalytic reaction preparation 3 - cyclopentyl - 3 - oxo third nitrile, then 3 - cyclopentyl - 3 - oxo third nitrile enzyme catalytic asymmetric reduction to generate chiral alcohols (S) - 3 - cyclopentyl - 3 - hydroxy propionitrile; (S) - 3 - cyclopentyl - 3 - hydroxy propionitrile by the Mitsunobu reaction and 4 - bromine pyrazole coupling get Russo advantage for Nepal intermediate (3R) - 3 - (4 - bromo - 1H - pyrazole - 1 - yl) - 3 - cyclopentane isopropyl amine; the synthesis method has the short route, the cost is low, mild condition, stereoselectivity is good, is suitable for the industrial production of the advantages. (by machine translation)

Regio- and Enantioselective Synthesis of N-Substituted Pyrazoles by Rhodium-Catalyzed Asymmetric Addition to Allenes

Abstract The rhodium-catalyzed asymmetric N-selective coupling of pyrazole derivatives with terminal allenes gives access to enantioenriched secondary and tertiary allylic pyrazoles, which can be employed for the synthesis of medicinally important targets. The reaction tolerates a large variety of functional groups and labelling experiments gave insights into the reaction mechanism. This new methodology was further applied in a highly efficient synthesis of JAK 1/2 inhibitor (R)-ruxolitinib.

PROCESSES FOR PREPARING JAK INHIBITORS AND RELATED INTERMEDIATE COMPOUNDS

The present invention is related to processes for preparing chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines of Formula III, and related synthetic intermediate compounds. The chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines are useful as inhibitors of the Janus Kinase family of protein tyrosine kinases (JAKs) for treatment of inflammatory diseases, myeloproliferative disorders, and other diseases.

Enantioselective synthesis of janus kinase inhibitor INCB018424 via an organocatalytic aza-michael reaction

An enantioselective synthesis of INCB018424 via organocatalytic asymmetric aza-Michael addition of pyrazoles (16 or 20) to (E)-3- cyclopentylacrylaldehyde (23) using diarylprolinol silyl ether as the catalyst was developed. Michael adducts (R)-24 and (R)-27 were isolated in good yield and high ee and were readily converted to INCB018424.