357336-99-3

Basic information

• Product Name: Brivaracetam (alfaR, 4S)-Isomer
• Synonyms: Brivaracetam (alfaR, 4S)-Isomer;2R-2-[(4S)-2-oxo-4-propylpyrrolidin-1-yl]butanamide
• CAS NO: 357336-99-3
• Molecular Formula: C11H20N2O2
• Molecular Weight: 212.29
• Mol File: 357336-99-3.mol

Chemical Properties

• Boiling Point: 409.3±28.0 °C(Predicted)
• Appearance: /
• Density: 1.062±0.06 g/cm3(Predicted)
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 15.74±0.50(Predicted)
• CAS DataBase Reference: Brivaracetam (alfaR, 4S)-Isomer(CAS DataBase Reference)
• NIST Chemistry Reference: Brivaracetam (alfaR, 4S)-Isomer(357336-99-3)
• EPA Substance Registry System: Brivaracetam (alfaR, 4S)-Isomer(357336-99-3)

Safety Data

• Hazardous Substances Data: 357336-99-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Brivaracetam (alfaR, 4S)-Isomer is used as a reagent for the preparation of 2-Oxo-1-pyrrolidine derivatives, which possess anticonvulsant activity. This application is significant in the development of new medications for the treatment of epilepsy and other seizure disorders.
Additionally, as an impurity of Brivaracetam (B677645), the alfaR, 4S)-Isomer plays a role in the production process of this anticonvulsant medication, contributing to its overall effectiveness in managing epilepsy.

Upstream product

• 7324-11-0 (S)-2-amino-butanamide 
• 357337-00-9 ((2R)-2-[(4R)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl]butanamide) 
• 357336-99-3 C₁₁H₂₀N₂O₂ 
• 21963-27-9 4-propyl-5H-furan-2-one 
• 78920-10-2 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one 
• 664305-06-0 3-(iodomethyl)hexanoic acid 
• 357338-44-4 5-hydroxy-4-propyldihydrofuran-2-one 
• 357338-13-7 (2S)-4,5-dehydro-(2-oxo-4-n-propyl-1-pyrrolidinyl)-2-butanamide 
• 110-62-3 pentanal 

Downstream Products

• 357336-99-3 ((2S)-2-[(4S)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl]butanamide) 
• 357337-00-9 ((2R)-2-[(4R)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl]butanamide) 
• 357336-99-3 ((2R)-2-[(4S)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl]butanamide) 
• 357336-20-0 brivaracetam 
• 357336-99-3 C₁₁H₂₀N₂O₂ 

Relevant articles and documents

Chiral resolution method of brivaracetam

The invention relates to a chiral resolution method of brivaracetam. The chiral resolution method comprises the following steps: 1) in a solvent, co-crystallizing a compound (R,S)-2-((R)-2-oxo-4-propyl pyrrolidin-1-yl)butyramide as shown in a formula 2 and D-tartaric acid to obtain a compound as shown in a formula 3; 2) performing alkali dissociation on the compound as shown in the formula 3 to obtain a compound as shown in a formula 1; and 3) carrying out epimerization on the other diastereoisomer compound as shown in the formula 4 in the step 1) under the action of alkali to obtain a compound as shown in the formula 2, and continuously preparing the compound as shown in the formula 1. According to the method, brivaracetam and diastereoisomers can be separated easily and conveniently, so high-purity brivaracetam is prepared.

Novel preparation method of brivaracetam

The invention provides a preparation method of brivaracetam. The method is characterized in that (R)-4-propyldihydro-2 (3H)-ketone purchased on the market is used as a raw material to synthesize brivaracetam in two steps under certain conditions. According to the preparation method disclosed by the invention, a chiral preparative chromatographic column separation step is not needed, and brivaracetam with high optical purity can be directly obtained; and the method is high in yield, simple and convenient in post-treatment, low in production cost and suitable for industrial production.

Intermediate for synthesizing brivaracetam and preparation method thereof

The invention provides an intermediate compound for synthesizing brivaracetam, namely (2S)-2-(5-oxy-3-propyl-2, 5-dihydrofuran-2-yl) amino) butylamide (I), and a preparation method of the intermediatecompound. The compound (I) comprises (S)-2(((R)-5-oxy-3-propyl-2, 5-dihydrofuran-2-yl) amino) butyramide (I)-R, or (S)-2-(((S)-5-oxy-3-propyl-2, 5-dihydrofuran-2-yl) amino) butyramide (I)-S, or a mixture of (I)-R and (I)-S in any proportion. The compound shown in the formula (I) can be used for synthesizing brivaracetam, and a novel method is provided for designing a concise and efficient brivaracetam synthesis route.

PROCESS FOR THE PREPARATION OF BRIVARACETAM

The present invention relates to a process for the preparation of brivaracetam, a compound of formula I and salts thereof. The present invention also relates to a compound of formula II and a compound of formula IIA, process for its preparation and conversion thereof to brivaracetam, the compound of formula I.

Novel preparation process of brivaracetam

The invention relates to the technical field of pharmacy, in particular to a novel brivaracetam preparation process, which utilizes L-2-aminobutanamide and 3-halogenated methylene-hexanoyl halide to directly obtain brivaracetam, avoids the use of a phase transfer catalyst, improves the product yield, simplifies the process steps and improves the production efficiency. The method comprises the following steps: S1, taking R-4-n-propyl-dihydrofuran-2-ketone as a raw material, and carrying out a halogenated acylation reaction in a halogenated acylation solvent to prepare 3-halogenated methylene-hexanoyl halide; S2, by taking the 3-halogenated methylene-hexanoyl halide as a substrate, carrying out reaction and post-treatment in the presence of a single organic solvent without a phase transfer catalyst under an alkaline condition to obtain brivaracetam.

Ligand Enabled Pd(II)-Catalyzed γ-C(sp3)-H Lactamization of Native Amides

γ-Lactams form important structural cores of a range of medicinally relevant natural products and clinical drugs, principal examples being the new generation of immunomodulatory imide drugs (IMiDs) and the brivaracetam family. Compared to conventional multistep synthesis, an intramolecular γ-C-H amination of aliphatic amides would allow for the direct construction of valuable γ-lactam motifs from abundant amino acid precursors. Herein we report a novel 2-pyridone ligand enabled Pd(II)-catalyzed γ-C(sp3)-H lactamization of amino acid derived native amides, providing the convenient synthesis of γ-lactams, isoindolinones, and 2-imidazolidinones. C6-Substitution of the 2-pyridone ligand is crucial for the lactam formation. This protocol features the use of N-acyl amino acids, which serve as both the directing group and cyclization partner, practical and environmentally benign tert-butyl hydrogen peroxide (TBHP) as the sole bystanding oxidant, and a broad substrate scope. The utility of this protocol was demonstrated through the two-step syntheses of a lenalidomide analog and brivaracetam from readily available carboxylic acids and amino acids.

A NEW COST EFFECTIVE AND SCALABLE PROCESS FOR SYNTHESIZING PURE BRIVARACETAM

The present invention relates to novel, economical processes for the preparation of enantiomerically pure Brivaracetam of Formula I having 99-100% diastereomeric excess (de) from its (R)-lactone intermediate that is (4R)-4-propyldihydrofuran-2(3H)-one.

Preparation methods of brivaracetam and intermediate thereof

The invention discloses a preparation method of a brivaracetam intermediate as shown in a formula B-R. The preparation method comprises the following steps: reacting a compound as shown in a formula B-P with a resolution reagent to prepare a compound as shown in a formula B-Q; and converting the compound as shown in the formula B-Q into the brivaracetam intermediate as shown in the formula B-R. The resolution reagent is a (1S, 2S)-(+)-1, 2-cyclohexanediamine compound. The invention also provides a preparation method of brivaracetam. According to the methods, a mixture of two diastereoisomers of (S)-2-3-propylpyrrolidine-1-yl butyric acid can be conveniently and effectively split, a chiral chromatographic column is not used, the process time is greatly shortened, the operation is simplified, the process cost is reduced, and industrial production and environmental protection are facilitated.

Novel preparation method of iracetam

The preparation method comprises the following steps: (R)-4 -propyl dihydrogen -2 (3H) - ketone which is purchased in the market as a raw material under a certain condition, and three-step synthesis of iracetam. To the preparation method provided by the invention, a chiral preparative chromatographic column separation step is not needed, and high optical purity Biracetam can be obtained directly. The method is high in yield. Post-treatment is simple and convenient, low in production cost, is fit for industrial production.

Identification, characterization, synthesis and strategy for minimization of potential impurities observed in the synthesis of brivaracetam

A first systematic impurity profile research concerning nine observed and potential process related impurities of antiepileptic drug brivaracetam is reported. Among which three (impurity G/H/I) have not been discovered or reported before, these nine impurities were monitored by HPLC, and their structures were identified on the basis of MS and NMR spectroscopy. In addition to the formation, synthesis, and characterization, strategies for minimizing these impurities to the levels accepted by ICH are also described in this report.