920274-03-9

Basic information

• Product Name: (R)-2-(3-Fluorophenyl)pyrrolidine
• Synonyms: (R)-2-(3-Fluorophenyl)pyrrolidine;(2R)-2-(3-fluorophenyl)pyrrolidine;Pyrrolidine,2-(3-fluorophenyl)-, (2R)-;(R)-2-(3-Fluorophenyl)pyrrolidine, HCl
• CAS NO: 920274-03-9
• Molecular Formula: C10H12FN
• Molecular Weight: 165.21
• Product Categories: pharmaceutical intermediate
• Mol File: 920274-03-9.mol

Chemical Properties

• Boiling Point: 232.3 °C at 760 mmHg
• Flash Point: 94.3 °C
• Appearance: /
• Density: 1.078 g/cm³
• Vapor Pressure: 0.0595mmHg at 25°C
• Refractive Index: 1.515
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 9.58±0.10(Predicted)
• CAS DataBase Reference: (R)-2-(3-Fluorophenyl)pyrrolidine(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-2-(3-Fluorophenyl)pyrrolidine(920274-03-9)
• EPA Substance Registry System: (R)-2-(3-Fluorophenyl)pyrrolidine(920274-03-9)

Safety Data

• Hazardous Substances Data: 920274-03-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(R)-2-(3-Fluorophenyl)pyrrolidine is used as a building block for the synthesis of biologically active molecules, leveraging its unique structure to contribute to the development of new drugs and therapeutic agents.
Used in Drug Design:
(R)-2-(3-Fluorophenyl)pyrrolidine is utilized as a component in drug design, where its chiral nature and specific interactions can be harnessed to create novel pharmaceutical compounds with targeted effects.
Used in Chemical and Biological Research:
(R)-2-(3-Fluorophenyl)pyrrolidine serves as a research tool in chemical and biological studies, providing insights into the behavior of chiral compounds and their interactions with biological systems, which can inform the design of more effective and selective drugs.
While the specific applications and therapeutic uses of (R)-2-(3-Fluorophenyl)pyrrolidine are still under investigation, its potential in various scientific and industrial applications is evident, making it a compound of significant interest for future research and development.

InChI:InChI=1/C10H12FN/c11-9-4-1-3-8(7-9)10-5-2-6-12-10/h1,3-4,7,10,12H,2,5-6H2/t10-/m1/s1

Upstream product

• 1196552-03-0 3-chloro-N-(3-fluorobenzylidene)propan-1-amine 
• 455-38-9 3-fluorobenzoic acid 
• 1073-06-9 3-fluorobromobenzene 
• 1223405-24-0 tert-butyl (4-(3-fluorophenyl)-4-oxobutyl)carbamate 
• 17318-03-5 bromo(3-fluorophenyl)magnesium 
• 456-48-4 3-Fluorobenzaldehyde 
• 164737-45-5 2-(3-fluorophenyl)-Δ¹-pyrroline 
• 451-02-5 ethyl 3-fluorobenzoate 

Downstream Products

• 1581686-73-8 2-(2-(3-fluorophenyl)pyrrolidin-1-yl)quinoline N-oxide 
• 1365221-52-8 N-(4-fluorobenzyl)-6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine-3-carboxamide 
• 1365212-65-2 6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine-3-carboxamide 
• 1365214-89-6 6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine-3-carboxylic acid 

Relevant articles and documents

Rational drug design to explore the structure-activity relationship (SAR) of TRK inhibitors with 2,4-diaminopyrimidine scaffold

Tropomyosin receptor kinase (TRK) is an ideal target for treating cancers caused by the NTRK gene fusion. In this study, more than 60 2,4-diaminopyrimidine derivatives were prepared to understand the structure-activity relationship and confirm the rationality of the pharmacophore model reported previously. Among them, compound 19k was found to be a potent pan-TRK inhibitor that inhibits the proliferation of Km-12 cell lines. Additionally, compound 19k induced the apoptosis of Km-12 cells in a concentration-dependent manner. Western blot analysis revealed that compound 19k inhibited the phosphorylation of TRK to block downstream pathways. Compound 19k also possessed outstanding plasma stability and liver microsomal stability in vitro, with half-lives greater than 289.1 min and 145 min, respectively. Pharmacokinetic studies indicated that the oral bioavailability of compound 19k is 17.4%. These results demonstrate that compound 19k could serve as a novel lead compound for overcoming NTRK-fusion cancers.

Stereocomplementary Synthesis of Pharmaceutically Relevant Chiral 2-Aryl-Substituted Pyrrolidines Using Imine Reductases

Exploring a collection of naturally occurring imine reductases (IREDs) identified two stereocomplementary IREDs with reducing activity toward sterically hindered 2-aryl-substituted pyrrolines. Using (R)-selective ScIR and (S)-selective SvIR, various chiral 2-aryl-substituted pyrrolidines with excellent enantioselectivity (>99% ee) were stereocomplementarily synthesized in good yield (60-80%), demonstrating the feasibility of IREDs for generating pharmaceutically relevant chiral 2-aryl-substituted pyrrolidine intermediates.

Design, synthesis and biological evaluation of N-hydroxy-aminobenzyloxyarylamide analogues as novel selective κ opioid receptor antagonists

Aminobenzyloxyarylamide derivatives 1a-i and 2a-t were designed and synthesized as novel selective κ opioid receptor (KOR) antagonists. The benzoyl amide moiety of LY2456302 was changed into N-hydroxybenzamide and benzisoxazole-3(2H)-one to investigate whether it could increase the binding affinity or selectivity for KOR. All target compounds were evaluated in radioligand binding assays for opioid receptor binding affinity. These efforts led to the identification of compound 1c (κ Ki = 179.9 nM), which exhibited high affinity for KOR. Moreover, the selectivity of KOR over MOR and DOR increased nearly 2-fold and 7-fold, respectively, compared with (±)LY2456302.

Enantioselective Synthesis of 2-Substituted Pyrrolidines via Intramolecular Reductive Amination

Catalyzed by the complex generated in situ from iridium and the chiral ferrocene ligand, tert -butyl (4-oxo-4-arylbutyl)carbamate substrates were deprotected and then reductively cyclised to form 2-substituted arylpyrrolidines in a one-pot manner, in which the intramolecular reductive amination was the key step. A range of chiral 2-substituted arylpyrrolidines were synthesised in up to 98percent yield and 92percent ee.

Preparation method of (R)-2-(2-substitution-5-fluorobenzene)pyrrolidine

The invention belongs to the technical field of organic synthesis, and provides a preparation method of (R)-2-(2-substitution-5-fluorobenzene)pyrrolidine. The preparation method comprises the following steps of: taking 2-substitution-5-fluorobenzaldehyde

Enantioselective Direct Synthesis of Free Cyclic Amines via Intramolecular Reductive Amination

Chiral cyclic amines can be prepared via intramolecular reductive amination of N-Boc-protected amino ketones in a one-pot process. With the complex of iridium and f-spiroPhos as the catalyst, a range of N-Boc-protected amino ketones are smoothly transformed into chiral cyclic free amines in high yields and excellent enantioselectivities (up to 97% ee). Moreover, this method can also be successfully applied to the synthesis of a κ-opioid receptor selective antagonist, (S)-1.

A Kinome-Wide Selective Radiolabeled TrkB/C Inhibitor for in Vitro and in Vivo Neuroimaging: Synthesis, Preclinical Evaluation, and First-in-Human

The proto-oncogenes NTRK1/2/3 encode the tropomyosin receptor kinases TrkA/B/C which play pivotal roles in neurobiology and cancer. We describe herein the discovery of [11C]-(R)-3 ([11C]-(R)-IPMICF16), a first-in-class positron emission tomography (PET) TrkB/C-targeting radiolabeled kinase inhibitor lead. Relying on extensive human kinome vetting, we show that (R)-3 is the most potent and most selective TrkB/C inhibitor characterized to date. It is demonstrated that [11C]-(R)-3 readily crosses the blood-brain barrier (BBB) in rodents and selectively binds to TrkB/C receptors in vivo, as evidenced by entrectinib blocking studies. Substantial TrkB/C-specific binding in human brain tissue is observed in vitro, with specific reduction in the hippocampus of Alzheimer's disease (AD) versus healthy brains. We additionally provide preliminary translational data regarding the brain disposition of [11C]-(R)-3 in primates including first-in-human assessment. These results illustrate for the first time the use of a kinome-wide selective radioactive chemical probe for endogenous kinase PET neuroimaging in human.

Design, synthesis and biological evaluation of aminobenzyloxyarylamide derivatives as selective κ opioid receptor antagonists

Opioid receptors play an important role in both behavioral and mood functions. Based on the structural modification of LY2456302, a series of aminobenzyloxyarylamide derivatives were designed and synthesized as κ opioid receptor antagonists. The κ opioid receptor binding ability of these compounds were evaluated with opioid receptors binding assays. Compounds 1a-d showed high affinity for κ opioid receptor. Especially for compound 1c, exhibited a significant Kivalue of 15.7?nM for κ opioid receptor binding and a higher selectivity over μ and δ opioid receptors compared to (±)LY2456302. In addition, compound 1c also showed potent κ antagonist activity with κ IC50?=?9.32?nM in [35S]GTP-γ-S functional assay. The potential use of the representative compounds as antidepressants was also investigated. The most potent compound 1c not only exhibited potent antidepressant activity in the mice forced swimming test, but also displayed the effect of anti-anxiety in the elevated plus-maze test.

Synthesis of chiral cyclic amines via Ir-catalyzed enantioselective hydrogenation of cyclic imines

A highly enantioselective hydrogenation of cyclic imines for synthesis of chiral cyclic amines has been realized. With the complex of iridium and (R,R)-f-spiroPhos as the catalyst, a range of cyclic 2-aryl imines were smoothly hydrogenated under mild conditions without any additive to provide the corresponding chiral cyclic amines with excellent enantioselectivities of up to 98% ee. Moreover, this method could be successfully applied to the synthesis of (+)-(6S,10bR)-McN-4612-Z.

COMPOUNDS AND COMPOSITIONS AS TRK INHIBITORS

The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated TRK kinase activity.