1421312-34-6

Basic information

• Product Name: fg-4592 int 2
• Synonyms: fg-4592 int 2;methyl 4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carboxylate;1 - methyl - 4 - hydroxy - 7 - phenoxy isoquinoline - 3 - methyl formate;4-Hydroxy-1-methyl-7-phenoxy-3-isoquinolinecarboxylic acid methyl ester;Fg-4592/FG4592 int 2
• CAS NO: 1421312-34-6
• Molecular Formula: C₁₈H₁₅NO₄
• Molecular Weight: 309.316
• EINECS: -0
• Product Categories: API
• Mol File: 1421312-34-6.mol

Chemical Properties

• Boiling Point: 537.3±45.0 °C(Predicted)
• Appearance: /
• Density: 1.289±0.06 g/cm3(Predicted)
• PKA: 6.24±0.50(Predicted)
• CAS DataBase Reference: fg-4592 int 2(CAS DataBase Reference)
• NIST Chemistry Reference: fg-4592 int 2(1421312-34-6)
• EPA Substance Registry System: fg-4592 int 2(1421312-34-6)

Safety Data

• Hazardous Substances Data: 1421312-34-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
fg-4592 int 2 is used as a reagent for the preparation of Roxadustat (H948180), a drug that is utilized in the treatment of anemia and chronic renal insufficiency. Its role in the synthesis process is crucial, as it contributes to the development of a medication that can help improve the quality of life for patients suffering from these conditions.

Upstream product

• 32852-92-9 3'-phenoxyacetophenone 
• 2142-63-4 1-(3-Bromophenyl)ethanone 
• 2440-79-1 N-acetyl-L-tyrosine methyl ester 
• 101630-75-5 methyl 2-acetamido-3-(4-phenoxyphenyl)methyl propionate 
• 60-18-4 L-tyrosine 
• 1080-06-4 L-Tyr-OMe 
• 99548-55-7 4-bromo-2-methyl-benzoic acid methyl ester 
• 68837-59-2 4-bromo-2-methylbenzoic acid 
• 1450-75-5 5-Bromo-2-hydroxyacetophenone 
• 1537180-08-7 C₂₂H₁₉NO₇ 
• 1509958-20-6 1-((acetoxy)methyl)-4-hydroxy-7-phenoxyisoquinolinyl-3-carboxylic acid methyl ester 
• 1509958-19-3 1-((dimethylamino)methyl)-4-hydroxy-7-phenoxyisoquinolinyl-3-carboxylic acid methyl ester 
• 64169-34-2 5-bromophthalide 

Downstream Products

• 808118-40-3 [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid 
• 1421312-35-7 4-hydroxy-1-methyl-7-phenoxy-3-isoquinolinecarboxylic acid 
• 1421312-36-8 [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)amino]acetic acid methyl ester 

Relevant articles and documents

Preparation method of roxadustat intermediate

The invention discloses a preparation method of a roxadustat intermediate. The method comprises the following steps: anhydride ring opening, esterification, ring closing, aromatization, deprotection, chlorination and methylation to obtain the roxadustat intermediate. According to the invention, the preparation method provided by the invention makes full use of the atom economy theory, is easy to operate, low in cost and low in pollution, and is suitable for large-scale industrial production; and only one-time refining is carried out, the chromatographic purity can reach 99.5% or above, and the total yield of the six-step reaction is 30% or above.

Preparation method of isoquinoline derivative

Disclosed is a preparation method of an isoquinoline derivative. A preparation method of a compound represented by a general formula II, i.e., 4-hydroxy-1-methyl-7-phenoxy isoquinoline-3-formate, is provided, wherein substituent definitions are as defined in the specification. The preparation method comprises the following steps of: under an acidic condition, dissolving a compound shown as a structural formula III in dimethyl sulfoxide, catalyzing by a ferrous ion (Fe) catalyst, and oxidizing by H2O2 to obtain the 4-hydroxy-1-methyl- 7-phenoxy isoquinoline-3-formate shown as the structuralformula II. By using the method, the production efficiency can be greatly improved, the production cost is reduced, the product purity can be ensured, and the method is suitable for industrial mass production.

Preparation method of roxadustat intermediate

The invention discloses a preparation method of a roxadustat intermediate, which comprises the following steps of: firstly, reacting methyl nitroacetate with trimethyl orthoformate to obtain a product I, and performing catalytic hydrogenation reduction to obtain a product II; then reacting the product II with m-phenoxyacetophenone to obtain a product III; carrying out a Pomeranz-Fritsch reaction on the product III, and completing intramolecular ring closing to obtain a product IV; finally, carrying out an oxidation reaction on the product IV to obtain the roxadustat intermediate 1-methyl-4-hydroxy-7-phenoxy isoquinoline-3-methyl carboxylate. According to the preparation method of the roxadustat intermediate, the raw materials are easy to obtain, and the production cost can be remarkably reduced. The whole process is simple, the whole consumed time is short, the production efficiency is high, the yield is high, the reaction condition is mild, the post-treatment is simple and convenient, and the method is suitable for large-scale preparation and has a great application prospect.

Method suitable for industrial production of roxadustat intermediate

The invention discloses a preparation method of a roxadustat intermediate. 4-hydroxy-1-methyl-7-phenoxy-3-isoquinoline carboxylic ester (IV) is a key intermediate for preparing roxadustat. The preparation method comprises the steps of (1) reacting a compound I and a compound II in an organic solvent under the catalysis of acid to prepare an intermediate III; and (2) carrying out cyclization reaction on the intermediate III in an organic solvent and a catalytic system to prepare the roxadustat intermediate IV. The preparation method of the roxadustat intermediate has the advantages that the raw materials are easy to obtain, the operation steps are few, the process is simple, the reaction yield is high, the atom utilization rate is high, and industrial production is easy.

Preparation method of bleomycin

The invention discloses a preparation method of Roxadustat, compound 1 and bis(dimethylamino)methane are heated in a mixed solvent of acetic acid and trifluoroacetic acid for reaction to form compound2; acetic anhydride is added to the obtained reaction solution of the compound 2 for completing reaction by heating to form compound 3; the compound 3 is dissolved in ethyl acetate and heated, then is catalyzed by Pd/C, and reduced by hydrogen to obtain compound 4; the compound 4 and glycine are dissolved in a solvent, and heated under the action of an organic base for reaction to obtain compound5; wherein the solvent is one or more of dioxane, ethylene glycol monomethyl ether, toluene, acetonitrile and n-propanol, the organic base is one or more of triethylamine, 1,8-diazabicyclo undecane-7-ene, N,N-diisopropylethylamine, N-methylmorpholine, pyridine, and ethylenediamine; the preparation method has the advantages of shorter reaction time, low reaction temperature, low equipment condition requirements and high crude product purity, is suitable for large-scale industrial production, and has a good industrialization prospect.

PROCESS OF MAKING ROXADUSTAT

The invention relates to a method of manufacturing roxadustat of formula (I), comprising the conversion of a compound of formula (VI) to roxadustat, R being an alkyl group in C1- C20 and PG being a protective group.

A General Organocatalytic System for Electron Donor-Acceptor Complex Photoactivation and Its Use in Radical Processes

We report herein a modular class of organic catalysts that, acting as donors, can readily form photoactive electron donor-acceptor (EDA) complexes with a variety of radical precursors. Excitation with visible light generates open-shell intermediates under mild conditions, including nonstabilized carbon radicals and nitrogen-centered radicals. The modular nature of the commercially available xanthogenate and dithiocarbamate anion organocatalysts offers a versatile EDA complex catalytic platform for developing mechanistically distinct radical reactions, encompassing redox-neutral and net-reductive processes. Mechanistic investigations, by means of quantum yield determination, established that a closed catalytic cycle is operational for all of the developed radical processes, highlighting the ability of the organic catalysts to turn over and iteratively drive every catalytic cycle. We also demonstrate how the catalysts' stability and the method's high functional group tolerance could be advantageous for the direct radical functionalization of abundant functional groups, including aliphatic carboxylic acids and amines, and for applications in the late-stage elaboration of biorelevant compounds and enantioselective radical catalysis.

Preparation method of isoquinolinone compound

The invention relates to a preparation method of an isoquinolinone compound. Specifically, the method for preparing the compound shown in the formula 2 comprises the step that a compound shown in a formula b reacts with a methylation reagent to obtain the compound shown in the formula 2. The method provided by the invention is used for preparing the isoquinolinone compound (such as Roxadustat), and has the excellent effects of reasonable route, convenience, feasibility, high yield, high purity, suitability for industrial production and the like.

Preparation method of Roxadustat intermediate

The invention provides a preparation method of a Roxadustat intermediate, and particularly relates to a preparation method of a Roxadustat intermediate 4-hydroxy-1-methyl-7-phenoxy-3-isoquinoline carboxylate. The preparation method comprises the following steps: carrying out a halogenation reaction on 4-hydroxy-1-hydrogen-7-phenoxy-3-isoquinoline carboxylate and a halogenating agent in the presence of a solvent to prepare 4-hydroxy-1-chloro/bromo/iodine-7-phenoxy-3-isoquinoline carboxylate, and further carrying out a methylation reaction in the presence of a catalyst, an alkali and a solvent to prepare 4-hydroxy-1-methyl-7-phenoxy-3-isoquinoline carboxylate. The preparation method provided by the invention has the advantages of easily available raw materials, mature and controllable process route and high reaction yield so as to be beneficial to industrial production of bulk drugs.

Preparation method of roxadustat

The invention relates to a preparation method of roxadustat. In the method, methyl 4-hydroxy-7-phenoxyisoquinoline-3-formate and N,N,N',N'-tetramethyldiaminomethane as raw materials are reacted in glacial acetic acid and methyl 1-((dimethylamino) methyl)-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate is obtained after the reaction is finished; the obtained methyl 1-((dimethylamino) methyl)-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate is dissolved into glacial acetic acid, zinc is added, diluted hydrochloric acid is added, and after the reaction is finished, methyl 4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carboxylate is obtained; the obtained methyl 4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carboxylate is mixed with glycine, and dissolved into methanol, sodium methoxide is added, and after the reaction is finished, the target product roxadustat is obtained. The method is mild in reaction condition, simple and controllable in operation, low in preparation cost and suitable for large-scale industrial production, the obtained target product is high in purity, and the production requirements of enterprises are met.