Chlorination of 2-Thiophenecarboxylic Acid

Bunnett, J. F.; Bachman, Daniel M.; Snipper, L. P.; Maloney, J. H.

doi:10.1021/ja01172a502

Cited by 12 publications

(5 citation statements)

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“…Some of the compounds, notably 2c,d and s, showed significant in vivo activity and these require further studies in order to evaluate their potential for development. Flavone-8-acetic Acid Derivatives phene-3-carboxylic acid readily gave the precursors to 5m and 5n, treatment of thiophene-2-carboxylic acid with sodium hypochlorite which is reported [9] to give 5-chlorothiophene-2-carboxylic acid, the precursor to 5s, was found to be unsatisfactory and this was better prepared from 2-chlorothiophene by bromination, lithium-halogen exchange and carboxylation. Similarly direct chlorination of thiophene-3carboxylic acid which is reported [10] to give either the 5chloro-or 2,5-dichloro-product was found to be difficult to control and, in our hands, gave only the trichloroacid corresponding to 5o.…”

Section: Synthesismentioning

confidence: 99%

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 31): 2-Heteroaryl Derivatives

Aitken

Bibby

Double

et al. 1998

Arch. Pharm. Pharm. Med. Chem.

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A range of 14 derivatives of flavone‐8‐acetic acid (FAA) with a heterocyclic substituent in place of the 2‐phenyl group have been prepared and their anti‐tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. Some of the compounds, notably 2c, d and s, showed significant in vivo activity and these require further studies in order to evaluate their potential for development.

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Section: Synthesismentioning

confidence: 99%

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 31): 2-Heteroaryl Derivatives

Aitken

Bibby

Double

et al. 1998

Arch. Pharm. Pharm. Med. Chem.

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“…The layers were separated and the aqueous phase purified by HPLC. Prepared according to general procedure (A) from 3-(methylthio)thiophene-2-carboxylic acid 27 and 7.4-{2-[1-Methyl-4-(1-methyl-4-(1-methyl-4-(5-chlorothiophene-2-carboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido]-ethyl}morpholine (79).Prepared according to general procedure (A) from 5-chlorothiophene-2-carboxylic acid (Lancaster) and 7Prepared according to general procedure (A) from 4,5-dichlorothiophene-2carboxylic acid28 and 7. 4-{2-[1-Methyl-4-(1-methyl-4-(1-methyl-4-(3-chloro-4-(propane-2-sulfonyl)-thiophene-2-carboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido]ethyl}morpholine (82).…”

mentioning

confidence: 99%

DNA Binding Ligands Targeting Drug-Resistant Bacteria: Structure, Activity, and Pharmacology

Kaizerman

Gross

et al. 2003

J. Med. Chem.

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We describe the lead optimization and structure-activity relationship of DNA minor-groove binding ligands, a novel class of antibacterial molecules. These compounds have been shown to target A/T-rich sites within the bacterial genome and, as a result, inhibit DNA replication and RNA transcription. The optimization was focused on N-terminal aromatic heterocycles and C-terminal amines and resulted in compounds with improved in vivo tolerability and excellent in vitro antibacterial potency (MIC >/= 0.031 microg/mL) against a broad range of Gram-positive pathogens, including drug-resistant strains such as methicillin-resistant Stapylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant Enterococcus faecalis (VRE). In a first proof-of-concept study, a selected compound (35) showed in vivo efficacy in a mouse peritonitis model against methicillin-sensitive S. aureus infection with an ED(50) value of 30 mg/kg.

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“…The straightforward one-stage ways to the target compound are chlorination − of thiophene-2-carboxylic acid (Scheme , Route A) or carboxylation of 2-chlorothiophene (Scheme , Route B, X = H), − since both starting materials are readily available. Direct halogenation of thiophene-2-carboxylic acid with chlorine was reported as early as 1934, but no yield was given.…”

Section: Building Blocksmentioning

confidence: 99%

“…Direct halogenation of thiophene-2-carboxylic acid with chlorine was reported 70 as early as 1934, but no yield was given. Another preparation of the title compound was conducted 71 with NaOCl as the chlorinating agent, and a 46% yield was obtained on a small scale. Recently, chlorination of the acid with isocyanuric chloride under three sets of conditions was published.…”

Section: Reduction Of Mfnnomentioning

confidence: 99%

Review on Synthetic Approaches toward Rivaroxaban (Xarelto), an Anticoagulant Drug

Mladentsev

Kuznetsova

Skvortsova

et al. 2022

Org. Process Res. Dev.

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Venous thromboembolism including deep vein thrombosis and pulmonary embolism is an abundant and dangerous disease with significant relapse probability and mortality. In pursuit of an effective treatment, Bayer created Rivaroxaban, nowadays known under the brand name Xarelto, that was approved by the FDA in 2011. By 2022, the number of main indications for the drug has been increased 10-fold as well as the drug's prevalence in the field of thrombosis treatment. It is therefore apparent that with growing prescriptions new synthetic pathways are highly desirable, especially those utilizing inexpensive and safe reagents in environmentally benign protocols. The present work reviews the literature concerning Rivaroxaban preparation with an emphasis on the applicability of synthetic pathways on a large scale. Within the synthetic sequences, common intermediates are discussed in detail and relevant comparisons are made. Our main purpose is to provide an overview of the subject in its current state, paying attention to advances made and suggesting possible directions for further development.

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Chlorination of 2-Thiophenecarboxylic Acid

Cited by 12 publications

References 0 publications

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 31): 2-Heteroaryl Derivatives

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 31): 2-Heteroaryl Derivatives

DNA Binding Ligands Targeting Drug-Resistant Bacteria: Structure, Activity, and Pharmacology

Review on Synthetic Approaches toward Rivaroxaban (Xarelto), an Anticoagulant Drug

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