22518-27-0

Usage

Uses

Used in Pharmaceutical Industry:
4-(4-Chlorophenyl)-2-pyrrolidinone is used as a key intermediate in the synthesis of various pharmaceutical compounds. Its chemical structure allows it to be a building block for the development of new drugs with specific therapeutic applications.
Used in Antagonist Preparation:
4-(4-Chlorophenyl)-2-pyrrolidinone is used as a starting material for the preparation of potential and selective antagonists of the α1A adrenergic receptor. These antagonists can be beneficial in treating various conditions related to the adrenergic system, such as hypertension and benign prostatic hyperplasia.
Used in Muscle Relaxant Formulation:
As an impurity of Baclofen (B108000), a specific GABA-B receptor agonist, 4-(4-Chlorophenyl)-2-pyrrolidinone contributes to the muscle relaxant properties of the drug. It is particularly useful in the treatment of skeletal muscle spasms and spasticity, providing relief and improved mobility for patients.

InChI:InChI=1/C10H10ClNO/c11-9-3-1-7(2-4-9)8-5-10(13)12-6-8/h1-4,8H,5-6H2,(H,12,13)

Upstream product

• 1134-47-0 4-amino-3-(4-chlorophenyl)butanoic acid 
• 81187-93-1 4-(4-chlorophenyl)-1,5-dihydro-2H-pyrrol-2-one 
• 152714-07-3 3-(4-chlorophenyl)cyclobutanone 
• 407-25-0 trifluoroacetic anhydride 
• 1073-67-2 4-vinylbenzyl chloride 
• 99-91-2 para-chloroacetophenone 
• 1267109-05-6 3-(4-chloro-phenyl)-3-cyano-propanoic acid methyl ester 
• 1679-18-1 4-Chlorophenylboronic acid 
• 706-07-0 1-chloro-4-(2-nitrovinyl)benzene 
• 52927-44-3 dimethyl 2-(4-chlorobenzylidene)malonate 
• 360072-54-4 methyl 2-carbomethoxy-4-nitro-3-(4-chloro-phenyl)-butyrate 
• 104-88-1 4-chlorobenzaldehyde 
• 6048-06-2 ethyl-p-chlorocinnamate 
• 81187-90-8 (Z)-4-Bromo-3-(4-chloro-phenyl)-but-2-enoic acid 

Downstream Products

• 137427-79-3 4-(4-chlorophenyl)-1-(4-methoxybenzoyl)-pyrrolid-2-one 
• 70206-22-3 Baclofen hydrochloride 
• 113933-11-2 2-[4-(p-chlorophenyl)-2-oxopyrrolidin-1-yl]-acetic acid ethyl ester 
• 1147392-44-6 4-(4'-(2-((R)-2-methylpyrrolidin-1-yl)ethyl)biphenyl-4-yl)pyrrolidin-2-one 
• 120418-62-4 3-(4-chlorophenyl)pyrrolidine 
• 1134-47-0 4-amino-3-(4-chlorophenyl)butanoic acid 

Relevant academic research and scientific papers

A facile synthesis of 3-aryl pyroglutamic acid. Facile synthesis of baclofen and chlorpheg

A facile synthesis of 3-aryl pyroglutamic acids via stepwise [3+2] annulation and desulfonated hydrolysis is reported. Base-induced coupling/cyclization reactions of α-sulfonylacetamide with various β-functional groups of (Z)-2-bromoacrylates yielded three contiguous chiral centers on the polysubstituted pyroglutamates system with trans-trans orientation in a one-pot synthesis. This facile strategy was used to synthesize amino acid derivatives baclofen and chlorpheg.

Rapid and Mild Lactamization Using Highly Electrophilic Triphosgene in a Microflow Reactor

Lactams are cyclic amides that are indispensable as drugs and as drug candidates. Conventional lactamization includes acid-mediated and coupling-agent-mediated approaches that suffer from narrow substrate scope, much waste, and/or high cost. Inexpensive, less-wasteful approaches mediated by highly electrophilic reagents are attractive, but there is an imminent risk of side reactions. Herein, a methods using highly electrophilic triphosgene in a microflow reactor that accomplishes rapid (0.5–10 s), mild, inexpensive, and less-wasteful lactamization are described. Methods A and B, which use N-methylmorpholine and N-methylimidazole, respectively, were developed. Various lactams and a cyclic peptide containing acid- and/or heat-labile functional groups were synthesized in good to high yields without the need for tedious purification. Undesired reactions were successfully suppressed, and the risk of handling triphosgene was minimized by the use of microflow technology.

Assembling of medium/long chain-based β-arylated unnatural amino acid derivatives via the Pd(II)-catalyzed sp3 β-C-H arylation and a short route for rolipram-type derivatives

In this paper, we report the assembling of libraries of β-arylated short/medium/long chain-based non-α-amino acid (aminoalkanoic acid) derivatives via the Pd(II)-catalyzed, bidentate directing group 8-aminoquinoline-aided sp3 β-C-H activation/arylation method. Short/medium chain-based unnatural amino acid derivatives containing an aryl group at the β-position are promising small molecules with therapeutic properties. Thus, it is necessary to enrich the libraries of short/medium/long chain-based unnatural amino acid derivatives containing an aryl group at the β-position. Considering the importance of β-arylated short/medium/long chain-based non-α-amino acid derivatives, an inclusive attention was paid to explore the Pd(II)-catalyzed sp3 β-C-H arylation of short/medium/long chain-based non-α-amino acids. Representative synthetic transformations including a short route for the assembling of rolipram and related compounds and 3-arylated GABA derivatives such as, baclofen, phenibut and tolibut were shown using selected β-C-H arylated non-α-amino acid derivatives.

New multicomponent reaction for the direct synthesis of β-aryl-γ-nitroesters promoted by hydrotalcite-derived mixed oxides as heterogeneous catalyst

A new approach based on multicomponent/domino combined reactions for the synthesis of γ-nitroesters promoted by a mixed aluminium-magnesium oxides derived from hydrotalcite-like material was developed. Different γ-nitroesters were synthesized in 15-95percent yield using Meldrum's acid, aromatic aldehydes, nitromethane and different alcohols as reagents and solvents. The γ-aminobutyric acid derivatives, Phenibut and Baclofen, were prepared in 63 and 61percent overall yield, respectively, through a two steps synthetic strategy. A mechanistic pathway was proposed based on the gas chromatography mass spectrometry (GC-MS) and electrospray ionization mass spectrometry (ESI-MS) experiments.

Efficient synthesis of β-aryl-γ-lactams and their resolution with (S)-Naproxen: Preparation of (R)- and (S)-Baclofen

An efficient synthesis of enantiomerically-pure β-aryl-γ-lactams is described. The principal feature of this synthesis is the practical resolution of β-aryl-γ-lactams with (S)-Naproxen. The procedure is based on the Michael addition of nitromethane to benzylidenemalonates, which was easily obtained, followed by the reduction of the γ-nitroester in the presence of Raney nickel and the subsequent saponification/decarboxylation reaction. The utility of this methodology was highlighted by the preparation of enantiomerically-pure (R)- and (S)-Baclofen hydrochloride.

One pot domino reaction accessing γ-nitroesters: Synthesis of GABA derivatives

Michael addition of 1,3-dicarbonyl compounds to nitrostyrenes is efficiently promoted by hydrotalcite [Mg-Al] to afford the respective γ-nitrodicarbonyl adducts. Differently, the addition of Meldrum's acid leads to a direct access of γ-nitroesters through a one pot domino process. GABA derivatives (+/-)-phenibut and (+/-)-baclofen were readily synthesized from the respective nitro adducts.

Multisite organic-inorganic hybrid catalysts for the direct sustainable synthesis of GABAergic drugs

Multisite organic-inorganic hybrid catalysts have been prepared and applied in a new general, practical, and sustainable synthetic procedure toward industrially relevant GABA derivatives. The domino sequence is composed of seven chemical transformations which are performed in two one-pot reactions. The method produces both enantiomeric forms of the product in high enantiopurity as well as the racemate in good yields after a single column purification step. This protocol highlights major process intensification, catalyst recyclability, and low waste generation.

β-Substituted γ-butyrolactams from mucochloric acid: Synthesis of (±)-baclofen and other γ-aminobutyric acids and useful building blocks

In the course of our exploration of the application of mucohalic acids in organic synthesis, we reported the synthesis of α,β-dihalo-α, β-unsaturated γ-butyrolactams by reductive amination of a suitable mucohalic acid and a suitable amine. However, the functionalization of the α- and/or β-halogen was found to be elusive under Suzuki conditions that worked well with the corresponding γ-lactones. Although the corresponding β-aryl derivative was obtained under some of the modified Suzuki conditions tried, the yields were found to be very low. Next, the Suzuki coupling was performed on mucochloric acid prior to the reductive amination step. By careful control of the reaction conditions, only β-substitution was achieved to yield the corresponding β-aryl mucochloric acid. This could then be converted to the corresponding β-substituted γ-butyrolactam by reductive amination with 2,4-dimethoxybenzylamine (DMB-NH2) followed by reduction by nickel boride and subsequent deprotection of the DMB group. The resulting γ-butyrolactam could either be alkylated or hydrolyzed resulting in the corresponding β-substituted γ-aminobutyric acid. This methodology was extended to synthesize (±)-baclofen in five steps starting from mucochloric acid.

ALLOSTERIC PROTEIN KINASE MODULATORS

The invention provides specific small molecule compounds that allosterically regulate the activity or modulate protein-protein interactions of AGC protein kinases and the Aurora family of protein kinases, methods for their production, pharmaceutical compositions comprising same, and their use for preparing medicaments for the treatment and prevention of diseases related to abnormal activities of AGC protein kinases or of protein kinases of the Aurora family.

ALLOSTERIC PROTEIN KINASE MODULATORS

The invention provides specific small molecule compounds that allosterically regulate the activity or modulate protein-protein interactions of AGC protein kinases and the Aurora family of protein kinases, methods for their production, pharmaceutical compositions comprising same, and their use for preparing medicaments for the treatment and prevention of diseases related to abnormal activities of AGC protein kinases or of protein kinases of the Aurora family.