165049-28-5

Basic information

• Product Name: N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid 1,5-diethyl ester 4-methylbenzenesulfonate
• Synonyms: N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid 1,5-diethyl ester 4-methylbenzenesulfonate;(S)-Diethyl 2-(4-(2-(2-aMino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyriMidin-5-yl)ethyl)benzaMido)pentanedioate 4-Methylbenzenesulfonate;N-[4-[2-(2-aMino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyriMidin-5-yl)ethyl]benzoyl]L-glutaMic acid;(2S)-2-{[4-(2-{2-aMino-4-oxo-3H,4H,7H-pyrrolo[2,3-d]pyriMidin-5-yl}ethyl)phenyl]forMaMido}pentanedioic acid;N-[4-[2-(2-aMino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyriMidin-5-yl)ethyl]benzoyl]L-glutaMic acid, 1,5-diethyl ester, 4-Methylbenzenesulfonate (1:1);(S)-Diethyl 2-(4-(2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)pe;PeMetrexed disodiuM INT-5;5-[2-(4-{[(1S)-4-ethoxy-1-(ethoxycarbonyl)-4-oxobutyl]carbaMoyl}phenyl)ethyl]-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyriMidin-2-aMiniuM 4-Methylbenzenesulfonate (non-preferred naMe)
• CAS NO: 165049-28-5
• Molecular Formula: C₇H₈O₃S*C₂₄H₂₉N₅O₆
• Molecular Weight: 655.725
• EINECS: 1806241-263-5
• Mol File: 165049-28-5.mol

Chemical Properties

• Appearance: /
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• Solubility: Dichloromethane (Very Slightly), DMF (Slightly, Sonicated), DMSO (Slightly)
• CAS DataBase Reference: N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid 1,5-diethyl ester 4-methylbenzenesulfonate(CAS DataBase Reference)
• NIST Chemistry Reference: N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid 1,5-diethyl ester 4-methylbenzenesulfonate(165049-28-5)
• EPA Substance Registry System: N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid 1,5-diethyl ester 4-methylbenzenesulfonate(165049-28-5)

Safety Data

• Hazardous Substances Data: 165049-28-5(Hazardous Substances Data)

Usage

Uses

Used in Oncology:
Pemetrexed is used as an antineoplastic agent for the treatment of malignant pleural mesothelioma (MPM), a rare and aggressive form of cancer that affects the lining of the lungs and chest cavity. It is also used in combination with other chemotherapy drugs for the treatment of non-small cell lung cancer (NSCLC) and other solid tumors.
Used in Drug Formulation:
Pemetrexed is formulated as a diethyl ester prodrug to improve its solubility and bioavailability. The 1,5-diethyl ester group enhances the compound's lipophilicity, allowing for better absorption and distribution in the body. Once inside the cells, the ester group is cleaved, releasing the active Pemetrexed molecule.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, Pemetrexed is used as an active pharmaceutical ingredient (API) in the development of cancer therapeutics. Its unique mechanism of action and ability to target multiple enzymes make it a valuable addition to the arsenal of cancer treatments.
Used in Research:
Pemetrexed is also used in research settings to study the molecular mechanisms of action of antifolate compounds and their potential applications in cancer therapy. It serves as a valuable tool for understanding the role of folate metabolism in cancer cell growth and survival.

InChI:InChI=1/C24H29N5O6.C7H8O3S/c1-3-34-18(30)12-11-17(23(33)35-4-2)27-21(31)15-8-5-14(6-9-15)7-10-16-13-26-20-19(16)22(32)29-24(25)28-20;1-6-2-4-7(5-3-6)11(8,9)10/h5-6,8-9,13,17H,3-4,7,10-12H2,1-2H3,(H,27,31)(H4,25,26,28,29,32);2-5H,1H3,(H,8,9,10)/t17-;/m0./s1

Upstream product

• 1118-89-4 diethyl-L-glutamate hydrochloride 
• 104-15-4 toluene-4-sulfonic acid 
• 106200-41-3 4-(4-carbomethoxyphenyl)butanal 
• 155405-79-1 4-(3-bromo-4-oxobutyl)benzoic acid methyl ester 
• 619-42-1 4-methoxycarbonylphenyl bromide 
• 123910-86-1 4-(4-hydroxybut-1-ynyl)benzoic acid methyl ester 
• 137281-39-1 4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl )ethyl]benzoic acid 
• 123910-88-3 methyl 4-(4-hydroxybut-1-yl)benzoate 
• 1209465-70-2 C₂₀H₁₉N₇O₅ 
• 13107-55-6 D-glutamic acid diethyl ester 
• 16450-41-2 L-glutamic acid diethyl ester 

Downstream Products

• 137281-23-3 pemetrexed 
• 869791-42-4 (2S)-2-[[4-[2-(2-amino-1-methyl-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino]pentanedioic acid 

Relevant articles and documents

Method for preparing pemetrexed disodium at high yield

The invention relates to a preparation method of pemetrexed disodium. The preparation method is characterized in that an alkali-modified microporous/mesoporous molecular sieve catalyst is used as a catalyst to replace NaOH as a reaction catalyst, so favorable yield and product purity are obtained under the condition of enlarged reaction scale.

Pemetrexed disodium intermediate and preparation method thereof

The invention belongs to the technical field of medicines, and particularly relates to a pemetrexed disodium intermediate III-1 and a preparation method thereof. The preparation method includes the steps: taking 4-[2-(2-amino-4, 7-dihydro-4-oxygen-3H-pyrr

Pemetrexed disodium intermediate and preparation method thereof

The invention belongs to the technical field of medicines, and particularly relates to a pemetrexed disodium intermediate III and a preparation method thereof. The preparation method includes the steps: adding 4-[2-(2-amino-4, 7-dihydro-4-oxygen-3H-pyrrolo[2, 3-d] pyrimidine-5-group) ethyl] benzoic acid into DMF (dimethyl formamide) and triethylamine, performing stirring and dissolving, performingreaction on mixture and R-CL, and treating a reactant to obtain an intermediate II; taking an intermediate I and the intermediate II as raw materials, performing condensation reaction under the action of N, N-carbonyl diimidazole, and performing reaction on the raw materials and p-toluenesulfonic acid to obtain the intermediate III. Amidogen is protected, impurities V generated by self-reaction are avoided, the problems of oxidation and discoloration caused by amidogen instability in reaction process are prevented, conditions are mild, yield is high, a product is stable, and practical production is facilitated.

Pemetrexed disodium intermediate and preparation method thereof

The invention belongs to the technical field of medicines, and particularly relates to a pemetrexed disodium intermediate II and a preparation method thereof. The preparation method includes the steps: adding 4-[2-(2-amino-4, 7-dihydro-4-oxygen-3H-pyrrolo[2, 3-d] pyrimidine-5-group) ethyl] benzoic acid into DMF (dimethyl formamide) and triethylamine; performing stirring and dissolving; dropping R-CL; performing heat preservation reaction; drying the DMF by distillation in a pressure reducing manner; adding pure water to stir mixture; adjusting pH (potential of hydrogen) by diluted hydrochloricacid to reach 5-6; performing stirring, crystallizing, extracting, filtering and drying to obtain the intermediate II. Preparation of the intermediate II is simpler, amidogen is protected, impuritiesV generated by self-reaction are avoided, the problems of oxidation and discoloration caused by amidogen instability in reaction process are prevented, conditions are mild, yield is high, a product is stable, and practical production is facilitated.

METHOD FOR PREPARING AN INTERMEDIATE FOR PRODUCING HIGH-PURITY PEMETREXED AND METHOD FOR PRODUCING HIGH-PURITY PEMETREXED USING THE INTERMEDIATE

Disclosed are a method for preparing an intermediate for producing high-purity pemetrexed and a method for producing high-purity pemetrexed using the intermediate, and more specifically, a method for preparing pemetrexed diethyl ester, which is an intermediate for producing pemetrexed, or a salt thereof with high purity, and to a method for producing pemetrexed disodium salt with high purity using the intermediate.

PROCESSES FOR PREPARING PEMETREXED DISODIUM AND ITS INTERMEDIATE,4-(4-CARBOMETHOXYPHENYL)BUTANAL

The present invention provides a process for preparing pemetrexed disodium and its intermediate, 4-(4-carbomethoxyphenyl)butanal. The process for preparing the intermediate comprises the following steps: condensing methyl 4-bromobenzoate with 3-buten-1-ol; extracting with an organic solvent during the work-up; adding silica gel to decolorize; and evaporating the organic solvent to give 4-(4-carbomethoxyphenyl)butanal. The product obtained by the present process, with a yield of higher than 80%, and a purity measured by GC of higher than 95%, may be directly used in the next bromination reaction for synthesizing pemetrexed disodium without purification. The present process is suitable for industrial production, as the operation is simple and the reagents used are cheap and readily available.

Crystalline forms of pemetrexed diacid and processes for the preparation thereof

Provided are crystalline forms of N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid, pemetrexed diacid, and processes for the preparation thereof.

Determination of the source of the N-methyl impurity in the synthesis of pemetrexed disodium heptahydrate

The synthesis of Pemetrexed Disodium Heptahydrate has consistently resulted in a very low level (ca. 0.02%) unknown impurity. To ensure long-term control, the identity and source of the impurity were desired. Isolation and characterization identified the impurity as the N-methyl derivative. The source was identified as the methyl groups on the peptide coupling agent, 2,6-Dimethoxy-1,3,5-triazine (CDMT). Further work assured the current conditions provide adequate control.

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.