72652-32-5

Usage

Uses

Used in Pharmaceutical Industry:
1-(4-BROMO-1H-PYRROL-2-YL)-2,2,2-TRICHLORO-1-ETHANONE is utilized as a building block for the synthesis of other organic compounds, contributing to the development of new medicinal agents. Its unique structure and properties play a crucial role in the creation of innovative pharmaceutical compounds with potential therapeutic applications.
Used in Research and Development:
In the field of research, 1-(4-BROMO-1H-PYRROL-2-YL)-2,2,2-TRICHLORO-1-ETHANONE serves as a key component in the synthesis of novel organic compounds. It is employed in various chemical reactions and processes to explore its potential applications and properties, furthering the understanding of its role in chemical and medicinal chemistry.
It is essential to handle 1-(4-BROMO-1H-PYRROL-2-YL)-2,2,2-TRICHLORO-1-ETHANONE with proper care and adhere to safety protocols due to its potential hazards and toxicity. This ensures the safety of researchers and the environment while working with this chemical compound.

InChI:InChI=1/C6H3BrCl3NO/c7-3-1-4(11-2-3)5(12)6(8,9)10/h1-2,11H

Upstream product

• 35302-72-8 pyrrol-2-yl trichloromethyl ketone 

Downstream Products

• 934-05-4 methyl 4-bromo-1H-pyrrole-2-carboxylate 
• 27746-02-7 4-bromo-1H-pyrrole-2-carboxylic acid 
• 1400875-70-8 4-(((1R)-1-cyclopropylethyl)amino)-6-phenylpyrrolo[1,2-b]pyridazine-3-carboxamide 
• 1400876-18-7 4-(((1R)-1-(1-fluorocyclopropyl)ethyl)amino)-6-phenylpyrrolo[1,2-b]pyridazine-3-carboxamide 
• 1400877-53-3 (S)-methyl 2-(6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-ylamino)-2-phenylacetate 
• 1400876-19-8 (S)-methyl 2-(3-carbamoyl-6-phenylpyrrolo[1,2-b]pyridazin-4-ylamino)-2-phenylacetate 
• 1400876-20-1 (S)-2-(3-carbamoyl-6-phenylpyrrolo[1,2-b]pyridazin-4-ylamino)-2-phenylacetic acid 
• 1400876-21-2 4-(((1S)-2-((cyanomethyl)amino)-2-oxo-1-phenylethyl)amino)-6-phenylpyrrolo[1,2-b]pyridazine-3-carboxamide 
• 1400877-58-8 6-bromo-4-(((1R)-1-(2-fluorophenyl)ethyl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide 
• 1400876-75-6 4-(((1R)-1-(2-fluorophenyl)ethyl)amino)-6-phenylpyrrolo[1,2-b]pyridazine-3-carboxamide 
• 1400876-80-3 6-phenyl-4-(propylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide 
• 1400877-61-3 4-methoxy-6-phenylpyrrolo[1,2-b]pyridazine-3-carboxamide 
• 1400876-81-4 4-(benzylamino)-6-phenylpyrrolo[1,2-b]pyridazine-3-carboxamide 
• 1400876-83-6 (R)-4-(1-cyclopropylethylamino)-6-(3-vinylphenyl)pyrrolo[1,2-b]pyridazine-3-carboxamide 

Relevant academic research and scientific papers

One-Pot Friedel-Crafts/Robinson-Gabriel Synthesis of the Indole-Oxazole Scaffold and Its Application to the Synthesis of Breitfussins C, G, and H

The indole-oxazole scaffold is found in a range of biologically active natural products, including the breitfussin family. Divergent methods that provide access to the indole-oxazole template are relatively scarce, which impedes the wider exploration of these natural products and their exciting biological activity. Herein, we describe a highly divergent synthesis of the indole-oxazole scaffold via a one-pot Friedel-Crafts/Robinson-Gabriel synthesis and the application of this methodology to the synthesis of breitfussins C, G, and H.

From Synthetic Simplified Marine Metabolite Analogues to New Selective Allosteric Inhibitor of Aurora B Kinase

Significant inhibition of Aurora B was achieved by the synthesis of simplified fragments of benzosceptrins and oroidin belonging to the marine pyrrole-2-aminoimidazoles metabolites isolated from sponges. Evaluation of kinase inhibition enabled the discovery of a synthetically accessible rigid acetylenic structural analogue EL-228 (1), whose structure could be optimized into the potent CJ2-150 (37). Here we present the synthesis of new inhibitors of Aurora B kinase, which is an important target for cancer therapy through mitosis regulation. The biologically oriented synthesis yielded several nanomolar inhibitors. The optimized compound CJ2-150 (37) showed a non-ATP competitive allosteric mode of action in a mixed-type inhibition for Aurora B kinase. Molecular docking identified a probable binding mode in the allosteric site "F"and highlighted the key interactions with the protein. We describe the improvement of the inhibitory potency and specificity of the novel scaffold as well as the characterization of the mechanism of action.

Synthesis and antibacterial analysis of analogues of the marine alkaloid pseudoceratidine

In an effort to gain more understanding on the structure activity relationship of pseudoceratidine 1, a di-bromo pyrrole spermidine alkaloid derived from the marine sponge Pseudoceratina purpurea that has been shown to exhibit potent biofouling, anti-fungal, antibacterial, and anti-malarial activities, a large series of 65 compounds that incorporated several aspects of structural variation has been synthesised through an efficient, divergent method that allowed for a number of analogues to be generated from common precursors. Subsequently, all analogues were assessed for their antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Overall, several compounds exhibited comparable or better activity than that of pseudoceratidine 1, and it was found that this class of compounds is generally more effective against Gram-positive than Gram-negative bacteria. Furthermore, altering several structural features allowed for the establishment of a comprehensive structure activity relationship (SAR), where it was concluded that several structural features are critical for potent anti-bacterial activity, including di-halogenation (preferable bromine, but chlorine is also effective) on the pyrrole ring, two pyrrolic units in the structure and with one or more secondary amines in the chain adjoining these units, with longer chains giving rise to better activities.

Substrate Controlled Regioselective Bromination of Acylated Pyrroles Using Tetrabutylammonium Tribromide (TBABr3)

Electrophilic bromination of pyrroles bearing carbonyl substituents at C-2 typically results in a mixture of the 4- and 5-brominated species, generally favoring the 4-position. Herein, we describe a substrate-controlled regioselective bromination in which

Synthesis and Absolute Stereochemical Reassignment of Mukanadin F: A Study of Isomerization of Bromopyrrole Alkaloids with Implications on Marine Natural Product Isolation

Synthesis of both enantiomers of mukanadin F was achieved by using a seven step synthesis. Comparison of the optical rotation data of synthetic samples to that reported for the isolated natural product determined that the absolute configuration of the natural product is 9S and not the reported 9R. Further studies established that the reported low magnitude of optical rotation in the isolated sample is due to compounds of this type undergoing isomerization and racemization under benign laboratory conditions. Additionally the synthetic methods developed were applied to synthesize mukanadins B and D.

Isolation, Derivative Synthesis, and Structure-Activity Relationships of Antiparasitic Bromopyrrole Alkaloids from the Marine Sponge Tedania brasiliensis

The isolation and identification of a series of new pseudoceratidine (1) derivatives from the sponge Tedania brasiliensis enabled the evaluation of their antiparasitic activity against Plasmodium falciparum, Leishmania (Leishmania) amazonensis, Leishmania (Leishmania) infantum, and Trypanosoma cruzi, the causative agents of malaria, cutaneous leishmaniasis, visceral leishmaniasis, and Chagas disease, respectively. The new 3-debromopseudoceratidine (4), 20-debromopseudoceratidine (5), 4-bromopseudoceratidine (6), 19-bromopseudoceratidine (7), and 4,19-dibromopseudoceratidine (8) are reported. New tedamides A-D (9-12), with an unprecedented 4-bromo-4-methoxy-5-oxo-4,5-dihydro-1H-pyrrole-2-carboxamide moiety, are also described. Compounds 4 and 5, 6 and 7, 9 and 10, and 11 and 12 have been isolated as pairs of inseparable structural isomers differing in their sites of bromination or oxidation. Tedamides 9+10 and 11+12 were obtained as optically active pairs, indicating an enzymatic formation rather than an artifactual origin. N12-Acetylpseudoceratidine (2) and N12-formylpseudoceratidine (3) were obtained by derivatization of pseudoceratidine (1). The antiparasitic activity of pseudoceratidine (1) led us to synthesize 23 derivatives (16, 17, 20, 21, 23, 25, 27-29, 31, 33, 35, 38, 39, 42, 43, 46, 47, 50, and 51) with variations in the polyamine chain and aromatic moiety in sufficient amounts for biological evaluation in antiparasitic assays. The measured antimalarial activity of pseudoceratidine (1) and derivatives 4, 5, 16, 23, 25, 31, and 50 provided an initial SAR evaluation of these compounds as potential leads for antiparasitics against Leishmania amastigotes and against P. falciparum. The results obtained indicate that pseudoceratidine represents a promising scaffold for the development of new antimalarial drugs.

Ni-Catalyzed C-H Functionalization in the Formation of a Complex Heterocycle: Synthesis of the Potent JAK2 Inhibitor BMS-911543

BMS-911543 is a complex pyrrolopyridine investigated as a potential treatment for myeloproliferative disorders. The development of a short and efficient synthesis of this molecule is described. During the course of our studies, a Ni-mediated C-N bond formation was invented, which enabled the rapid construction of the highly substituted 2-aminopyridine core. The synthesis of this complex, nitrogen-rich heterocycle was accomplished in only eight steps starting from readily available materials.

A Palladium(II)-Catalyzed C-H Activation Cascade Sequence for Polyheterocycle Formation

Polyheterocycles are found in many natural products and are useful moieties in functional materials and drug design. As part of a program towards the synthesis of Stemona alkaloids, a novel palladium(II)-catalyzed C-H activation strategy for the construction of such systems has been developed. Starting from simple 1,3-dienyl-substituted heterocycles, a large range of polycyclic systems containing pyrrole, indole, furan and thiophene moieties can be synthesized in a single step. Don't overdo it: A palladium(II)-catalyzed C-H activation cascade sequence for the synthesis of polyheterocycles is reported. Aromatization of the initially formed dihydro species occurred with a quinone oxidant. In some cases the use of one equivalent of the oxidant enabled isolation of the dihydro species as a single isomer (see scheme; X=NMe, O, S).

Non-basic azolotriazinone MCHR1 antagonists for the treatment of obesity: An empirical brain-exposures-driven candidate selection for in vivo efficacy studies

Non-basic azolotriazinones were explored using an empirical free brain exposures-driven approach to identify potent MCHR1 antagonists for evaluation in in vivo efficacy studies. An optimized lead from this series, 1j (rMCHR1 Ki = 1.8 nM), demonstrated a 6.9% reduction in weight gain relative to vehicle in a rat model at 30 mg/kg after 4 days of once-daily oral treatment as a glycine prodrug. Despite a promising efficacy profile, an assessment of the biliary toxicity risk of this compound rendered this compound non-progressible.

PROCESS FOR THE PREPARATION OF N,N-DICYCLOPROPYL-4-(1,5-DIMETHYL-1H-PYRAZOL-3-YLAMINO)-6-ETHYL-1-METHYL-1,6-DIHYDROIMIDAZO[4,5-d]PYRROLO[2,3-b]PYRIDINE-7-CARBOXAMIDE

The invention relates to an improved process for synthesizing N,N-dicyclopropyl-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide of the formula: (I) Compound (I) is currently in clinical trials for the treatment of myeloproliferative disorders, such as polycythaemia vera, thrombocythaemia and primary myelofibrosis.