106200-41-3

Usage

Uses

Used in Pharmaceutical Industry:
Methyl 4-(4-oxobutyl)benzoate is used as a reagent for the preparation of Pemetrexed (P219500), an antifolate and nitric oxide donor. It plays a vital role in the development of anticancer agents, specifically targeting enzymes involved in nucleotide synthesis, thereby inhibiting tumor growth and progression.
Additionally, Methyl 4-(4-oxobutyl)benzoate is utilized in the synthesis of furoxanoxyalkyl esters of Pemetrexed, which are also employed as anticancer agents. These compounds exhibit enhanced activity against cancer cells by combining the antifolate properties of Pemetrexed with the nitric oxide donor capabilities of the furoxanoxyalkyl group, leading to a more effective treatment option for various types of cancer.

Synthesis Reference(s)

Journal of Heterocyclic Chemistry, 23, p. 1, 1986 DOI: 10.1002/jhet.5570230101

Upstream product

• 615581-18-5 methyl 4-[3-(1,3-dioxolan-2-yl)propyl]benzoate 
• 123910-86-1 4-(4-hydroxybut-1-ynyl)benzoic acid methyl ester 
• 86608-70-0 2-(1,3-dioxolan-2-yl)ethyl(triphenyl)phosphonium bromide 
• 627-27-0 homoalylic alcohol 
• 619-42-1 4-methoxycarbonylphenyl bromide 
• 6108-17-4 lithium acetate dihydrate 
• 60-29-7 diethyl ether 
• 123910-88-3 methyl 4-(4-hydroxybut-1-yl)benzoate 
• 927-74-2 3-Butyn-1-ol 
• 619-44-3 methyl 4-iodobenzoate 
• 99768-12-4 4-methoxycarbonylphenylboronic acid 
• 64-18-6 formic acid 
• 20849-84-7 methyl 4-allylbenzoate 
• 57498-54-1 methyl 4-(4-methylphenyl)-4-oxobutanoate 

Downstream Products

• 229471-26-5 4-(4-hydroxy-5-nitropentyl)benzoic acid methyl ester 
• 134373-15-2 4-<2-(2,4-diamino-7H-pyrrolo<2,3-d>pyrimidin-5-yl)propyl>benzoic acid 
• 144051-63-8 4-[3-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)propyl]benzoic acid 
• 125991-54-0 diethyl N-<4-<3-(2-amino-4(3H)-oxo-7H-pyrrolo<2,3-d>pyrimidin-5-yl)propyl>benzoyl>-L-glutamate 
• 259145-26-1 4-[4-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-5-nitropentyl]benzoic acid methyl ester 
• 229471-28-7 4-[5-nitro-4-(2,4,6-triaminopyrimidin-5-yl)pentyl]benzoic acid methyl ester 
• 123910-88-3 methyl 4-(4-hydroxybut-1-yl)benzoate 
• 155405-79-1 4-(3-bromo-4-oxobutyl)benzoic acid methyl ester 
• 165049-28-5 pemetrexed diethyl ester p-toluenesulfonic acid salt 
• 1320346-37-9 C₁₂H₁₂Br₂O₃ 
• 1320346-43-7 methyl 4-[2-(2-amino-4,6-dioxo-4,5,6,7-tetrahydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)-ethyl]-benzoate 
• 193265-47-3 4-[2-(2-amino-4,6-dioxo-4,5,6,7-tetrahydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)-ethyl]-benzoic acid 
• 1320346-45-9 dimethyl 2-{4-[2-(2-amino-4,6-dioxo-4,5,6,7-tetrahydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)-ethyl]-benzoylamino}-pentanedioate 
• 193281-00-4 2-{4-[2-(2-amino-4,6-dioxo-4,5,6,7-tetrahydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)-ethyl]-benzoylamino}-pentanedioic acid 

Relevant academic research and scientific papers

A practical synthesis of multitargeted antifolate LY231514

A concise and scalable synthesis of LY231514 (1), a new pyrrolo[2,3-d]pyrimidine-based antitumor agent, is presented. Reaction of 2-bromo-4-arylbutanal 9 with 2,4-diamino-6-hydroxypyrimidinc (10) regioselectively provided pyrrolo[2,3-d]pyrimidine 11, representing the core structure of the drug, in good yield. Assimilation of the glutamic acid residue by conventional means completed the synthesis. Development of the optimized synthetic route emphasized avoiding isolation of the relatively unstable aldehyde and bromoaldehyde intermediates.

Synthesis and antiviral study of novel 4-(2-(6-amino-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-d]pyrimidin-3-yl)ethyl)benzamide derivatives

A series of ten new compounds (7a–j) has been synthesized by absolutely replacing the glutamic acid part of Pemetrexed drug, chemically known as N-{4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-l-glutamic acid, with primary, secondary, and aryl amines in high yields using diethylphosphorocyanidate (DEPC) as a peptide coupling agent. All the synthesized compounds are characterized by 1H and 13C NMR, LCMS, and FT-IR spectral techniques. All the synthesized novel non-glutamate 4-(2-(6-amino-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-d]pyrimidin-3-yl)ethyl)benzamide derivatives showed 4- to 7-folds higher antiviral activity than its structurally similar commercial drug Pemetrexed against Newcastle disease virus, an avian paramyxovirus. Among the lot, compounds possessing carboxamide synthesized using five-membered heteroaryl amines (7i and 7j) exhibited the highest antiviral activity. [Figure not available: see fulltext.].

An Efficient Synthesis of Pemetrexed Disodium

An efficient synthetic method for the pemetrexed disodium has been developed using methyl 4-iodobenzoate and 3-buten-1-ol as starting materials via six steps. The developed process avoided some tedious workup procedures and unfriendly reagents compared with the reported synthetic routes. In addition, two impurities generated in the process were isolated and characterized by 1H NMR, 13C NMR, and HRMS. The mechanisms of the two impurities were also discussed, and the impurities could be easily removed by suitable workup procedures. The overall yield of pemetrexed disodium was increased from 12.8% (literature) to 34.9%. Therefore, this cost-effective, environmental friendly, and high-yielding process is more suitable for scale-up production of pemetrexed disodium.

PdII-Catalyzed Site-selective β- and γ-C(sp3)-H Arylation of Primary Aldehydes Controlled by Transient Directing Groups

Pd(II)-catalyzed site-selective β- and γ-C(sp3)-H arylation of primary aldehydes is developed by rational design of L,X-type transient directing groups (TDG). External 2-pyridone ligands are identified to be crucial for the observed reactivity. By minimizing the loading of acid additives, the ligand effect is enhanced to achieve high reactivities of the challenging primary aldehyde substrates. Site selectivity can be switched from the proximate to the relatively remote position by changing the bite angle of TDG to match the desired palladacycle size. Experimental and computational investigations support this rationale for designing TDG to potentially achieve remote site-selective C(sp3)-H functionalizations.

Multi-arm polymeric prodrug conjugates of pemetrexed-based compounds

Among other aspects, provided herein are multi-arm polymeric prodrug conjugates of pemetrexed-based compounds. Methods of preparing such conjugates as well as methods of administering the conjugates are also provided. Upon administration to a patient, release of the pemetrexed-based compound is achieved.

Carbonylative Transformation of Allylarenes with CO Surrogates: Tunable Synthesis of 4-Arylbutanoic Acids, 2-Arylbutanoic Acids, and 4-Arylbutanals

In this Communication, procedures for the selective synthesis of 4-arylbutanoic acids, 2-arylbutanoic acids, and 4-arylbutanals from the same allylbenzenes have been developed. With formic acid or TFBen as the CO surrogate, reactions proceed selectively and effectively under carbon monoxide gas-free conditions.

Synthetic pemedolac preparation process

The invention discloses a synthetic pemedolac preparation method, which specifically comprises: carrying out a Heck reaction by using methyl p-bromobenzoate and 3-butene-1-ol as starting raw materialsto obtain crude aldehyde, and directly carrying out a bromination reaction, a cyclization reaction and a hydrolysis reaction through a one-pot method to obtain pemedolac. According to the present invention, the method has characteristics of mild reaction conditions, easy control, simple and safe process operation, good product yield and high product purity.

Method for preparing pemetrexed disodium key intermediate

The invention discloses a method for preparing a pemetrexed disodium key intermediate (I). The method comprises the following steps: carrying out classical Friedenylation and esterification reactionson raw materials comprising toluene and succinic anhydride to obtain methyl 3-(4-methylphenyl)-4-oxobutanoate, carrying out oxygen or air oxidation on the methyl 3-(4-methylphenyl)-4-oxobutanoate under the catalysis of N-hydroxyphthalimide (NHPI) and cobalt acetate to obtain 4-(methoxy-4-oxobutylcarbonyl)benzoic acid, and carrying out selective reduction, selective oxidation, esterification and bromination reactions on the obtained oxidation product to prepare methyl 4-(3-bromo-4-oxobutyl)benzoate. The method has the advantages of cheap and easily available raw materials, mild reaction conditions, simplicity in treatment, good yield and good purity of the product, and suitableness for industrial production.

INHIBITORS OF HISTONE LYSINE SPECIFIC DEMETHYLASE (LSD1) AND HISTONE DEACETYLASES (HDACS)

A series of phenelzine analogs comprising a phenelzine scaffold linked to an aromatic moiety and their use as inhibitors of lysine-specific demethylase 1 (LSD1) and/or one or more histone deacetylases (HDACs) is provided. The presently disclosed phenelzine analogs exhibit potency and selectivity for LSD1 versus MAO and LSD2 enzymes and exhibit bulk, as well as, gene specific histone methylation changes, anti-proliferative activity in several cancer cell lines, and neuroprotection in response to oxidative stress. Accordingly, the presently disclosed phenelzine analogs can be used to treat diseases, conditions, or disorders related to LSD1 and/or HDACs, including, but not limited to, cancers and neurodegenerative diseases.

PROCESS FOR THE PREPARATION OF PEMETREXED AND LYSIN SALT THEREOF

The present invention refers to a process for the synthesis of pemetrexed and salts thereof, in particular to a lysine salt thereof, to said salt as such and to pharmaceutical compositions that comprise the same. Furthermore, the present disclosure also relates to a crystalline form of the synthesis intermediate pemetrexed diethyl ether and a crystalline form of the pemetrexed lysine salt.