50727-04-3

Basic information

• Product Name: 5-methoxy-1h-isoindole-1,3(2h)-dione
• Synonyms: 5-methoxy-1h-isoindole-1,3(2h)-dione;5-methoxyisoindoline-1,3-dione;4-MethoxyphthaliMide;5-methoxyisoindole-1,3-dione
• CAS NO: 50727-04-3
• Molecular Formula: C₉H₇NO₃
• Molecular Weight: 177.15678
• EINECS: 1533716-785-6
• Mol File: 50727-04-3.mol

Chemical Properties

• Melting Point: 219 °C
• Appearance: /
• Density: 1.347g/cm³
• Refractive Index: 1.585
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 9.84±0.20(Predicted)
• CAS DataBase Reference: 5-methoxy-1h-isoindole-1,3(2h)-dione(CAS DataBase Reference)
• NIST Chemistry Reference: 5-methoxy-1h-isoindole-1,3(2h)-dione(50727-04-3)
• EPA Substance Registry System: 5-methoxy-1h-isoindole-1,3(2h)-dione(50727-04-3)

Safety Data

• Hazardous Substances Data: 50727-04-3(Hazardous Substances Data)

Usage

Uses

Used in Chemical Synthesis:
5-methoxy-1h-isoindole-1,3(2h)-dione is used as a reagent in the synthesis of KUP-1, a photoreactive and fluorescent pyrethroid. 5-methoxy-1h-isoindole-1,3(2h)-dione serves as a valuable tool for photoaffinity labelling, which is a technique used to study the interactions between molecules, particularly in biological systems.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 5-methoxy-1h-isoindole-1,3(2h)-dione may be utilized as a building block or intermediate in the development of new drugs. Its unique structure and reactivity can be exploited to create novel compounds with potential therapeutic applications.
Used in Research and Development:
5-methoxy-1h-isoindole-1,3(2h)-dione can also be employed in research and development settings, where it may be used to explore new chemical reactions, study the properties of related compounds, or investigate its potential applications in various fields, such as materials science or environmental chemistry.

InChI:InChI=1/C9H7NO3/c1-13-5-2-3-6-7(4-5)9(12)10-8(6)11/h2-4H,1H3,(H,10,11,12)

Upstream product

• 1885-13-8 4-methoxyphthalic acid 
• 7647-01-0 hydrogenchloride 
• 143956-83-6 N-(1,2,3,9-tetramethoxy-5,6-dihydro-7H-dibenzo[a,c][7]annulen-7-yl)acetamide 
• 5111-70-6 5-methoxy-1-indanone 
• 22479-95-4 dimethyl 4-hydroxyphthalate 
• 22895-19-8 dimethyl 4-methoxyphtalate 
• 134-08-7 4-sulpho-phthalic anhydride 
• 610-35-5 4-hydroxyphthalic acid 
• 85-44-9 phthalic anhydride 
• 42923-77-3 6-methoxy-1,2,3,4-tetrahydro-isoquinoline 
• 28281-76-7 5-methoxyisobenzofuran-1,3-dione 

Downstream Products

• 1603818-42-3 dimethyl (2S,4S)-2-(benzyloxy)-4-(5-methoxy-1,3-dioxoisoindolin-2-yl)-2-phenylcyclopentane-1,1-dicarboxylate 
• 1356116-35-2 methyl 4-methoxy-2-((methoxycarbonyl)amino)benzoate 
• 1356116-37-4 methyl 5-methoxy-2-((methoxycarbonyl)amino)benzoate 
• 22246-66-8 2,3-dihydro-5-methoxy-1H-isoindol-1-one 
• 127168-88-1 5-methoxy-2,3-dihydro-1H-isoindole 
• 22246-66-8 6-methoxy-2,3-dihydro-isoindol-1-one 

Relevant articles and documents

Synthesis method of phthalimide and phenyl ring-substituted phthalimide derivative

The invention provides a synthesis method of phthalimide and a phenyl ring-substituted phthalimide derivative. The synthesis method comprises that aromatic ketone and ammonia gas or an ammonia gas precursor as substrates and air or oxygen as an oxygen source undergo a reaction under catalyst action and liquid phase conditions to produce phthalimide and a phenyl ring-substituted phthalimide derivative. The synthesis method is mild, realizes high oxidation efficiency and a high product yield, utilizes oxygen or air as an oxygen source, is economic and eco-friendly and has a good application prospect.

Divergent Reactivity of Thioalkynes in Lewis Acid Catalyzed Annulations with Donor–Acceptor Cyclopropanes

Efficient methods for the convergent synthesis of (poly)cyclic scaffolds are urgently needed in synthetic and medicinal chemistry. Herein, we describe new annulation reactions of thioalkynes with phthalimide-substituted donor–acceptor cyclopropanes, which gave access to highly substituted cyclopentenes and polycyclic ring systems. With silyl-thioalkynes, the Lewis acid catalyzed [3+2] annulation reaction with donor–acceptor cyclopropanes took place to afford 1-thio-cyclopenten-3-amines. On the other hand, an unprecedented polycyclic compound was formed with alkyl-thioalkynes through a reaction pathway directly involving the phthalimide group. The two transformations proceeded in good yields and tolerated a large variety of functional groups.

Dynamic kinetic asymmetric [3 + 2] annulation reactions of aminocyclopropanes

We report the first example of a dynamic kinetic asymmetric [3 + 2] annulation reaction of aminocyclopropanes with both enol ethers and aldehydes. Using a Cu catalyst and a commercially available bisoxazoline ligand, cyclopentyl- and tetrahydrofurylamines were obtained in 69-99% yield and up to a 98:2 enantiomeric ratio using the same reaction conditions. The method gives access to important enantio-enriched nitrogen building blocks for the synthesis of bioactive compounds.

PHARMACEUTICAL COMPOUNDS

The invention provides a compound for use in medicine, the compound being a compound of the formula (VI0) or a salt, solvate, tautomer or N-oxide thereof: wherein the bicyclic group: is selected from the structures C1, C5 and C6: wherein n is 0, 1, 2 or 3; R1 is hydrogen, hydroxy, or O—Rz; R2a is hydroxy, methoxy or O—Rz; provided that at least one of R1 and R2a is O—Rz; Rz is Lp-Rp1; SO3H; a glucuronide residue; a mono-, di- or tripeptide residue; or Lp is a bond, C═O, (C═O)O, (C═O)NRp1 or S(O)xNRp1; x is 1 or 2; Rp1 is hydrogen or a an optionally substituted C1-25 hydrocarbyl group containing 0, 1 or 2 carbocyclic rings and 0, 1, 2, 3, 4, 5 or 6 carbon-carbon multiple bonds, provided that Rp1 is not hydrogen when Lp is a bond, C═O or (C═O)O; and provided also that O—Rz does not contain an O—O moiety; and excluding compounds wherein R1 is hydroxy and R2a is methoxy; Rp2 and Rp3 are the same or different and each is a group Rp1; and R3, R4a, R8 and R10 are defined in the claims. The compounds of formula (VI0) are pro-drugs of parent compounds wherein R1 and/or R2a are hydroxy, wherein the parent compounds have Hsp90 inhibiting activity.

Discovery of (2,4-Dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1- ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a novel inhibitor of the molecular chaperone Hsp90 by fragment based drug design

Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) are currently generating significant interest in clinical development as potential treatments for cancer. In a preceding publication (DOI: 10.1021/jm100059d) we describe Astex's approach to screening fragments against Hsp90 and the subsequent optimization of two hits into leads with inhibitory activities in the low nanomolar range. This paper describes the structure guided optimization of the 2,4-dihydroxybenzamide lead molecule 1 and details some of the drug discovery strategies employed in the identification of AT13387 (35), which has progressed through preclinical development and is currently being tested in man.

PHARMACEUTICAL COMBINATIONS

The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1- 5 hydrocarbyloxy; R4 is selected from hydrogen; a group -(O)n-R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 inhibitors.

PHARMACEUTICAL COMBINATIONS

The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1-5 hydrocarbyloxy; R4 is selected from hydrogen; a group -(O)n-R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 and/or glycogen synthase kinase-3 and/or cyclin dependent kinase inhibitors.

PHARMACEUTICAL COMBINATIONS

The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1-5 hydrocarbyloxy; R4 is selected from hydrogen; a group -(O)n-R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 and/or glycogen synthase kinase-3 and/or cyclin dependent kinase and/or aurora kinase inhibitors.

PHARMACEUTICAL COMPOUNDS

The invention provides the use of a compound for the manufacture of a medicament for the treatment of pain, wherein the compound is a compound of the formula (Vl): or a salt, solvate, tautomer or N-oxide thereof; wherein the bicydic group: is selected from the structures C1, C5 and C6: wherein n, R1, R2a, R3, R4a, R8 and R10 are as defined in the claims. The invention also provides the use of a compound of the formula (Vl) for the manufacture of a medicament for the prophylaxis or treatment of a fungal, protozoal, viral or parasitic disease state or condition (other than a disease state or condition due to Plasmodium falciparum) or for use in the prophylaxis or treatment of Ewing's sarcoma, atherosclerosis or lupus erythematosus