102308-43-0

Usage

Uses

Used in Pharmaceutical Synthesis:
4-Bromo-2-benzofuran-1(3H)-one is used as a versatile reactant in the preparation of Citalopram (C505000) analogs via Suzuki coupling. This application is significant for the development of new antidepressant medications, as Citalopram is a widely prescribed selective serotonin reuptake inhibitor (SSRI).
Used in Cardiovascular Applications:
In the pharmaceutical industry, 4-Bromo-2-benzofuran-1(3H)-one is used as a precursor in the synthesis of butylphthalide derivatives, which possess vasorelaxant activity. These compounds have potential applications in the treatment of cardiovascular diseases, as they can help to relax blood vessels and improve blood flow.
Used in Antibacterial Drug Development:
4-Bromo-2-benzofuran-1(3H)-one is also utilized in the synthesis of Pentacyclines, which are Tetracycline (T291400) analogs. Tetracyclines are a class of broad-spectrum antibiotics that are effective against a wide range of bacterial infections. The development of new analogs can help to address the growing issue of antibiotic resistance and provide alternative treatment options for various infections.
Overall, 4-Bromo-2-benzofuran-1(3H)-one plays a crucial role in the synthesis of various pharmaceutical compounds, with applications in the development of antidepressants, cardiovascular treatments, and antibacterial drugs. Its versatility as a reactant makes it a valuable component in the ongoing pursuit of new and effective medications.

InChI:InChI=1/C8H5BrO2/c9-7-3-1-2-5-6(7)4-11-8(5)10/h1-3H,4H2

Upstream product

• 59434-19-4 4-Amino-1(3H)-isobenzofuranon 
• 82-73-5 3-bromophthalic anhydride 
• 99548-54-6 methyl 3-bromo-2-methylbenzoate 
• 526-75-0 2,3-Dimethylphenol 
• 6296-53-3 3-acetylaminophthalic anhydride 
• 65399-18-0 4-nitrophthalide 
• 103260-67-9 4-acetylamino-phthalide 
• 76006-33-2 3-bromo-2-methylbenzoic acid 
• 50-00-0 formaldehyd 
• 153435-81-5 (3-bromophenyl)(morpholino)methanone 
• 87-41-2 2-benzofuran-1(3H)-one 
• 116-69-8 3-bromophthalic acid 
• 576-23-8 2,3-dimethylbromobenzene 

Downstream Products

• 90483-95-7 3-cyano-phthalide 
• 1287277-22-8 methyl 3-bromo-2-formylbenzoate 

Relevant academic research and scientific papers

Ligand-enabled pd(ii)-catalyzed c(sp3)-h lactonization using molecular oxygen as oxidant

Pd(II)-catalyzed C-H lactonization of o-methyl benzoic acid substrates has been achieved using molecular oxygen as the oxidant. This finding provides a rare example of C-H oxygenation through Pd(II)/Pd(0) catalysis as well as a method to construct biologically important benzolactone scaffolds. The use of a gas mixture of 5% oxygen in nitrogen demonstrated the possibility for its application in pharmaceutical manufacturing.

Synthesis of 3-Unsubstituted Phthalides from Aryl Amides and Paraformaldehyde via Ruthenium(II)-Catalyzed C–H Activation

A straightforward and convenient route has been developed for the synthesis of 3-unsubstituted phthalide derivatives from aryl amides and paraformaldehyde by ruthenium(II)-catalyzed C–H activation. The reaction proceeds through tandem ortho-hydroxymethylation of aryl amide and subsequent intramolecular lactonization.

Synthesis and biological activity of n-butylphthalide derivatives

A series of n-butylphthalide derivatives were designed and synthesized. The in vitro activities of these compounds were evaluated by a resting tension of isolated rat thoracic aorta ring assay. Compounds 4g and 4i were found to be more active than n-butylphthalide.

On the regioselectivity of metal hydride reductions of 3-substituted phthalic anhydrides

A problem of 3-methoxyphthalide reduction by metal hydrides was reinvestigated. Various effects controlling selectivity of reductions in 3-substituted phthalides were studied, and a qualitative interpretation of the results is now proposed. Methods for obtaining enhanced yields of one or the other lactonic product were developed.

Squaramide-catalyzed asymmetric intramolecular oxa-michael reaction of α,β-unsaturated carbonyls containing benzyl alcohol: Construction of chiral 1-substituted phthalans

Organocatalytic enantioselective intramolecular oxa-Michael reactions of benzyl alcohol bearing α,β-unsaturated carbonyls as Michael acceptors are presented herein. Using cinchona squaramide-based organocatalyst, enones as well as α,βunsaturated esters containing benzyl alcohol provided their corresponding 1,3-dihydroisobenzofuranyl-1-methylene ketones and 1,3-dihydroisobenzofuranyl-1-methylene esters in excellent yields with high enantioselectivities. In addition, enantioenriched 1,3-dihydroisobenzofuranyl-1-methylene ketone could be obtained from the Wittig/oxa-Michael reaction cascade of 1,3-dihydro-2-benzofuran-1-ol.

Palladium (II)-Catalyzed Decarboxylative Cross-Dehydrogenative Coupling: Direct Synthesis of meta-Substituted Biaryls from Aromatic Acids

A palladium-catalyzed tandem process of simple aromatic acids has been achieved to afford meta-substituted biaryls in moderate to good yields. The reaction proceeds via carboxyl-directed intermolecular cross-dehydrogenative coupling and subsequent decarboxylation. The new C?C bonds in this transformation are formed in the ortho position of carboxyl and the reaction tolerates electron-rich acids. Both symmetrical and unsymmetrical meta-substituted biaryls can be directly synthesized via this method. (Figure presented.).

BIARYL PHOSPHODIESTERASE 1NHIBITORS

Novel biaryl compounds with phosphodiesterase inhibitory activity of the general formula (I), wherein R1, R2, R3, X, Y, Z1, Z2, Z3, and Z4 have the meanings defined herein, as well as their use as therapeutic agents in the treatment of inflammatory diseases and conditions

Structure-activity relationships for a novel series of citalopram (1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5- carbonitrile) analogues at monoamine transporters

(±)-Citalopram (1, 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1, 3-dihydroisobenzofuran-5-carbonitrile), and its eutomer, escitalopram (S-(+)-1) are selective serotonin reuptake inhibitors (SSRIs) that are used clinically to treat anxiety and depression. To further explore structure-activity relationships at the serotonin transporter (SERT), a series of (±)-4- and 5-substituted citalopram analogues were designed, synthesized, and evaluated for binding at the SERT, dopamine transporter (DAT) and norepinephrine transporter (NET) in native rodent tissue. Many of these analogues showed high SERT binding affinities (Ki = 1-40 nM) and selectivities over both NET and DAT. Selected enantiomeric pairs of analogues were synthesized and both retained enantioselectivity as with S- and R-1, wherein S > R at the SERT. In addition, the enantiomeric pairs of 1 and 5 were tested for binding at the homologous bacterial leucine transporter (LeuT), wherein low affinities and the absence of enantioselectivity suggested distinctive binding sites for these compounds at SERT as compared to LeuT. These novel ligands will provide molecular tools to elucidate drug-protein interactions at the SERT and to relate those to behavioral actions in vivo.

Total synthesis and biological evaluation of 22-hydroxyacuminatine

A total synthesis of 22-hydroxyacuminatine, a cytotoxic alkaloid isolated from Camptotheca acuminata, is reported. The key step in the synthesis involves the reaction of 2,3-dihydro-1H-pyrrolo[3,4-b]quinoline with a brominated phthalide to generate a substituted pentacyclic 12H-5,11a-diazadibenzo[b,h] fluoren-11-one intermediate. Despite its structural resemblance to camptothecin and luotonin A, a biological evaluation of 22-hydroxyacuminatine in a topoisomerase I-deficient cell line P388/CPT45 has confirmed that the observed cytotoxicity is not due to topoisomerase I inhibition, even though 22-hydroxyacuminatine has a hydroxyl group that can theoretically hydrogen bond to Asp533. This result is consistent with the hypothesis that π-π stacking is more important than hydrogen-bonding interactions in determining topoisomerase I inhibitor binding in the ternary cleavage complex.

17O NUCLEAR MAGNETIC RESONANCE SPECTROSCOPIC STUDY OF SUBSTITUTED PHTHALIC ANHYDRIDES AND PHTHALIDES

17O chemical shift data (natural abundance) for 3-substituted phthalic anhydrides and 4- and 7-substituted phthalides in acetonitrile at 75 deg C are reported.Steric interactions of substituents ortho to the carbonyl groups result in deshielding effects (9-22 ppm) relative to parent compounds regardless of the electronic character of the substituents.Factors contributing to the deshielding effects are discussed.The relationship between 17O chemical shifts and regiochemistry of the phthalic anhydrides is discussed.