1919868-77-1

Usage

Uses

Used in Organic Synthesis:
(R)-2-(2,5-difluorophenyl)pyrrolidine (R)-2-hydroxysuccinate is used as a building block in organic synthesis for the creation of various complex organic molecules. Its unique structure allows for the formation of new chemical entities with potential applications in different industries.
Used in Medicinal Chemistry:
In the field of medicinal chemistry, (R)-2-(2,5-difluorophenyl)pyrrolidine (R)-2-hydroxysuccinate is used as a key intermediate in the synthesis of pharmaceutical compounds. Its specific structural features may contribute to the development of new drugs with improved therapeutic properties.
Used in Pharmaceutical Industry:
(R)-2-(2,5-difluorophenyl)pyrrolidine (R)-2-hydroxysuccinate is used as an active pharmaceutical ingredient (API) for the development of new medications. Its unique structure and properties may offer advantages in terms of efficacy, selectivity, and safety compared to existing drugs.
Used in Agrochemical Industry:
(R)-2-(2,5-difluorophenyl)pyrrolidine (R)-2-hydroxysuccinate is used as a starting material or intermediate in the synthesis of agrochemicals, such as pesticides and herbicides. Its potential applications in this industry may contribute to the development of more effective and environmentally friendly products.
Used in Chiral Catalysis and Asymmetric Synthesis:
The (R)-2-hydroxysuccinate group present in (R)-2-(2,5-difluorophenyl)pyrrolidine (R)-2-hydroxysuccinate makes it a valuable compound for chiral catalysis and asymmetric synthesis. It can be used as a chiral catalyst or ligand to facilitate the synthesis of enantiomerically pure compounds, which are essential in various applications, including pharmaceuticals and agrochemicals.
Further research and development of (R)-2-(2,5-difluorophenyl)pyrrolidine (R)-2-hydroxysuccinate could lead to its incorporation into various processes and products in the chemical industry, expanding its range of applications and contributing to the advancement of science and technology.

Upstream product

• 399-94-0 2-bromo-1,4-difluorobenzene 
• 636-61-3 D-Malic acid 
• 1443623-92-4 5-(2,5-difluorophenyl)-3,4-dihydro-2H-pyrrole 
• 1218935-59-1 (R)-(+)-2-(2,5-difluorophenyl)pyrrolidine 
• 2646-90-4 2,5-difluorobenzaldehyde 
• 1216260-42-2 4‐chloro‐1‐(2,5-difluorophenyl)butan-1-one 
• 886503-15-7 rac-2-(2,5-difluorophenyl)pyrrolidine 

Downstream Products

• 1223404-88-3 5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-amine 
• 1223405-08-0 (S)-N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate 
• 2135871-21-3 phenyl (5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate 
• 1218935-59-1 (R)-(+)-2-(2,5-difluorophenyl)pyrrolidine 

Relevant academic research and scientific papers

Racemization method of larotinib intermediate

The invention discloses a racemization method of a larotinib intermediate, which comprises the following steps: in a solvent, heating (2S)-2-(2, 5-difluorophenyl)pyrrolidine(compound I, S-type I) or aracemic mixture mainly comprising S-type I, and convert

Efficient preparation of (R)-2-(2,5-difluorophenyl)pyrrolidine via a recycle process of resolution

An efficient preparation of (R)-2-(2,5-difluorophenyl)pyrrolidine ((R)-1) from the racemate based on a recycle process of resolution/racemization was described. In the process, the desired (R)-1 was obtained by resolution with D-malic acid in 95% EtOH. Me

Synthesis method of (R)-2-(2, 5-difluorophenyl) pyrrolidine

The invention belongs to the technical field of chemical pharmacy, and relates to a synthetic method of (R)-2-(2, 5-difluorophenyl)pyrrolidine. The synthesis method comprises the following steps: (1) carrying out dehydration condensation reaction on a compound as shown in a formula 1 and a chiral induction reagent (R) tert-butylsulfinamide to obtain a compound as shown in a formula 2; (2) carrying out addition reaction on the compound in the formula 2 and a Grignard reagent to obtain a compound in a formula 3; (3) carrying out a reduction/cyclization reaction on the compound shown in the formula 3, trifluoroacetic acid and triethylsilane to obtain a compound shown in a formula 4; (4) splitting the compound shown in the formula 4 by (D)-malic acid to obtain the (R)-2-(2, 5-difluorophenyl) pyrrolidine*D malate compound with EE being greater than 98% shown in the formula 5; and (5) dissociating the compound in the formula 5 with a sodium hydroxide solution to obtain (R)-2-(2, 5-difluorophenyl) pyrrolidine. By utilizing the synthetic method of (R)-2-(2,5-difluorophenyl)pyrrolidine, the cost is low, the optical purity is high, the subsequent separation process is simplified, the raw materials are easy to obtain, the process conditions are mild, and the synthetic method is suitable for synthesizing (R)-2-(2, 5-difluorophenyl) pyrrolidine in large-scale production.

Preparation method of (R)-2-(2,5-difluorophenyl)-pyrrolidine

The invention discloses a preparation method of (R)-2-(2, 5-difluorophenyl)-pyrrolidine, and a preparation method of a compound represented by a formula III, wherein the method comprises the followingstep: in an organic solvent, carrying out a reaction defined in the specification on a compound represented by a formula II and a compound represented by a formula I to obtain a compound representedby the formula III at a high yield and a high ee value. The preparation method is simple in reaction condition, convenient to operate, low in cost and high in industrial value.

Method for preparing larotrectinib intermediate through one-pot method

The invention discloses a method for preparing a larotrectinib intermediate through a one-pot method. The preparation method is characterized by comprising the following steps: 1) dissolving a compound VI serving as a raw material in a solvent, adding isopropyl magnesium chloride to generate a Grignard reagent, and reacting with N-Boc-pyrrolidone to obtain a compound I; 2) adding an acid into thereaction solution, and carrying out a Boc removal reaction on the compound I to obtain a compound II; 3) adding an alkali into the reaction solution, and carrying out a ring closing reaction on the compound II to obtain a compound III; 4) carrying out reduction on the compound III in the reaction solution to obtain a compound IV; and 5) carrying out salification on the compound IV and D-malic acid, and re-crystallizing to obtain a compound V.

Enantioselective Imine Reduction Catalyzed by Phosphenium Ions

The first use of phosphenium cations in asymmetric catalysis is reported. A diazaphosphenium triflate, prepared in two or three steps on a multigram scale from commercially available materials, catalyzes the hydroboration or hydrosilylation of cyclic imin

Synthesis process of chiral pyrrolidine and intermediates

The invention discloses a synthesis process of chiral pyrrolidine and intermediates. The synthesis process adopts 2, 5-difluorohalobenze or 5-fluoro-3 halogenated pyridine as the raw material substrate, and employs a chiral catalyst to induce chiral react

PREPARATION OF (S)-N-(5-((R)-2-(2,5-DIFLUOROPHENYL)PYRROLIDIN-1-YL)PYRAZOLO[1,5-A]PYRIMIDIN-3-Y L)-3-HYDROXYPYRROLIDINE-1-CARBOXAMIDE

Process for preparing (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-l- yl)pyrazolo[l,5-a] pyrimidin-3-yl)-3-hydroxypyrrolidine-l-carboxamide (formula I) or a salt thereof by reacting phenyl(5-((R)-2-(2,5- difluorophenyl)pyrrolidin-l-yl)-3,3a-dihydropyrazolo[l,5-a]pyrimidin-3- yl)carbamate or a similar derivative (formula 13) with (S)-pyrrolidin-3- ol (formula 14). Process for preparing phenyl(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-l- yl)-3,3a-dihydropyrazolo[l,5-a]pyrimidin-3-yl)carbamate (formula 13) or a similar derivative by reduction of (R)-5-(2-(2,5-difluorophenyl) pyrrolidin-l-yl)-3-nitropyrazolo[l,5-a]pyrimidine (formula 11) to (R) -5-(2-(2,5-difluorophenyl)pyrrolidin-l-yl)pyrazolo[l,5-a]pyrimidin-3- amine (formula 12). Process for preparing (R)-2-(2,5-difluorophenyl)pyrrolidine(R) -2-hydroxysuccinate (formula 10) by treating (R)-N-((R)-l-(2,5- difluorophenyl)-3-(l,3-dioxan-2-yl)propyl)-2-methylpropane-2- sulfinamide (formula 19) with an acid and a reducing agent. (S)-N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-l-yl)-pyrazolo[l,5- a]pyrimidin-3-yl)-3-hydroxypyrrolidine-l-carboxamide, is a tyrosin kinase (TRK) inhibitor for trearing e.g. cancer.

METHODS OF TREATING PEDIATRIC CANCERS

A method of treating a pediatric cancer in a subject in need thereof. The method includes administering to the subject a therapeutically effective amount of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrro

CRYSTALLINE FORM OF (S)-N-(5-((R)-2-(2,5-DIFLUOROPHENYL)-PYRROLIDIN-1-YL)-PYRAZOLO[1,5-A]PYRIMIDIN-3-YL)-3-HYDROXYPYRROLIDINE-1-CARBOXAMIDE HYDROGEN SULFATE

A novel crystalline form of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or Trypanosoma cruzi infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.