14352-65-9

Usage

Appearance

White to off-white solid

Melting point

High

Stability

More stable than its parent compound, 2-(hydroxyimino)acetoacetic acid

Ease of handling

Easier to handle in various chemical reactions due to the presence of the tert-butyl ester group

Uses

Building block in the synthesis of various pharmaceuticals and organic compounds, key intermediate in the production of some pesticides

Hazard classification

Low hazard chemical with no known adverse effects on human health or the environment when used in accordance with recommended guidelines.

InChI:InChI=1/C8H13NO4/c1-5(10)6(9-12)7(11)13-8(2,3)4/h12H,1-4H3

Upstream product

• 1694-31-1 tert-butyl acetoacetate 
• 326914-14-1 5-(5-Bromo-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic Acid (2-dimethylamino-ethyl)amide 

Downstream Products

• 88055-48-5 benzyl 5'-t-butoxycarbonyl-3,3'-di(2-methoxycarbonylethyl)-4-methyl-4'-trideuteriomethylpyrromethane-5-carboxylate 
• 268544-50-9 C₁₁H₁₇NO₆ 
• 89909-48-8 3,5-dimethyl-1H-pyrrole-2, 4-dicarboxylic acid 2-tert-butyl ester 4-benzyl ester 
• 1309134-43-7 tert-butyl 8-(5-benzyloxycarbonyl-3-ethyl-4-methyl-2-pyrrolyl)-3-methylindeno[2,1-b]pyrrole-2-carboxylate 
• 945381-56-6 5-carboxymethyl-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 
• 86770-31-2 2-tert-butyl 4-ethyl 3,5-dimethyl-1H-pyrrole-2,4-dicarboxylate 
• 76674-93-6 tert-butyl 2-methoxyimino-3-oxobutyrate 
• 527384-78-7 t-butyl 2-(2-chlorophenyl)-5-methyl-1H-imidazole-4-carboxylate 
• 79491-18-2 benzyl 4,3'-di(2-acetoxyethyl)-5'-t-butoxycarbonyl-3,4'-dimethyl-2,2'-dipyrrylmethane-5-carboxylate 
• 590424-04-7 tert-butyl 4-[[[2-(diethylamino)ethyl]amino]carbonyl]-3,5-dimethyl-1H-pyrrole-2-carboxylate 
• 60024-89-7 4-(2-methoxycarbonylethyl)-3,5-dimethyl-1H-pyrrole-2-carboxylic acid tert-butyl ester 

Relevant academic research and scientific papers

Synthesis of [18F]SU11248, a new potential PET tracer for imaging cancer tyrosine kinase

N-[2-(Diethylamino)ethyl]-5-[(Z)-(5-[18F]fluoro-2-oxo-1, 2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide, a new potential positron emission tomography tracer for imaging cancer tyrosine kinase, has been prepared by the nucleophilic substitution of the nitro-precursor N-[2-(diethylamino)ethyl]-5-[(Z)-(5-nitro-2-oxo-1,2-dihydro-3H- indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide with K 18F/Kryptofix 2.2.2 followed by a simple chromatography methodology combined solid-phase extraction with high-performance liquid chromatography purification procedures in 15-25% radiochemical yields.

Novel potent orally active multitargeted receptor tyrosine kinase inhibitors: Synthesis, structure-activity relationships, and antitumor activities of 2-indolinone derivatives

The inhibition of receptor tyrosine kinases (RTKs) has become a successful approach in the development of anticancer agents. Many potent small-molecule kinase inhibitors have been discovered. We report herein a series of pyrrolo-fused-heterocycle-2-indolinone analogues as inhibitors of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and c-Kit. Among them, some pyrrolo-fused six- and seven-membered-heterocycle derivatives such as 9, 15, 23, and 25 are potent inhibitors of VEGFR, PDGFR, and c-Kit both enzymatically (50 nM) and cellularly (50 nM). Furthermore, compounds 9 and 25 possess favorable pharmacokinetic profiles and demonstrate good efficacies against human HT-29 cell colon tumor xenografts in nude mice. Further evaluations are in progress.

Early amidation approach to 3-[(4-amido)pyrrol-2-yl]-2-indolinones

A new synthesis of 3-[(4-amido)pyrrol-2-yl]-2-indolinones has been developed, where the amide side chain was installed prior to pyrrole formation. This strategy precludes the need to use any coupling reagents to install the amide side chain. This process includes a zinc-free alternative to the Knorr pyrrole synthesis.

Synthesis, biological evaluation, and in silico study of pyrazoline-conjugated 2,4-dimethyl-1H-pyrrole-3-carboxylic acid derivatives

A potential molecular hybridization strategy was used to develop 24 novel pyrazoline-conjugated 2,4-dimethyl-1H-pyrrole-3-carboxylic acid and amide derivatives. The preliminary in vitro antimicrobial assay delivered four potential derivatives with growth inhibition in the range of 50.87–56.60% at the concentration of 32 μg/ml. In the search of an anticancer candidate, all derivatives were screened by NCI-60 at 10 μM concentration, revealing that 12 derivatives were potential agents against the various types of cancer cell lines, with growth inhibition in the range of 50.21–108.37%. The in vitro cytotoxicity assay against the cell line HEK293 (human embryonic kidney cells) and the hemolysis assay of the representative potent compounds propose their potential for a good therapeutic index. In silico studies of the most potent derivatives qualified their significant pharmacokinetic properties with good predicted oral bioavailability and their adherence to Lipinski's rule of five for druglikeness. A molecular docking study against VEGFR-2 with the best-scored conformations reinforced their anticancer potency. The docking study of the most potent compound against VEGFR-2 with the best-scored conformations displayed a binding affinity (?9.5 kcal/mol) comparable with the drug sunitinib (?9.9 kcal/mol) and exhibited that tighter interactions at the active adenosine triphosphate site might be responsible for anticancer potency.

5-Hydroxy-7-azaindolin-2-one, a novel hybrid of pyridinol and sunitinib: Design, synthesis and cytotoxicity against cancer cells

Angiogenesis plays important roles in tumor growth and metastasis. Sunitinib (Sutent) is an antitumor agent targeting receptor tyrosine kinases which are involved in angiogenesis as well as cancer cell growth and survival. Using the pyridin-3-ol scaffold, which was previously reported as an excellent antioxidant and antiangiogenic platform, we have synthesized sunitinib mimics 6 by hybridizing bicyclic pyridinol 4 as a key scaffold and pyrrole-2-carbaldehydes 7 as side chains. Cytotoxicity assays showed that compounds 6 have comparable to better anticancer activity than sunitinib against five different cancer cell lines. In addition, compounds 6 showed even lower levels of cytotoxicity against normal cells, resulting in up to 26-fold better safety windows, than sunitinib. Signaling pathway-associated transcription factor reporter assay and western blot analyses revealed that apoptosis induction in MDA-MB-231 human breast cancer cells by 6F is mainly mediated through the p53 increase and down-regulation of phospho-signal transducer and activator of transcription 3 (STAT3) and its target gene products, cyclin D, Bcl-2, and survivin. The data strongly suggest that our hybrid compounds can provide a novel anticancer scaffold with improved and safer cytotoxicity profiles than sunitinib.

Hypochlorite-Mediated Modulation of Photoinduced Electron Transfer in a Phenothiazine–Boron dipyrromethene Electron Donor–Acceptor Dyad: A Highly Water Soluble “Turn-On” Fluorescent Probe for Hypochlorite

A highly water-soluble phenothiazine (PTZ)–boron dipyrromethene (BODIPY)-based electron donor–acceptor dyad (WS-Probe), which contains BODIPY as the signaling antennae and PTZ as the OCl? reactive group, was designed and used as a fluorescent chemosensor for the detection of OCl?. Upon addition of incremental amounts of NaOCl, the quenched fluorescence of WS-Probe was enhanced drastically, which indicated the inhibition of reductive photoinduced electron transfer (PET) from PTZ to 1BODIPY*; the detection limit was calculated to be 26.7 nm. Selectivity studies with various reactive oxygen species, cations, and anions revealed that WS-Probe was able to detect OCl? selectively. Steady-state fluorescence studies performed at varied pH suggested that WS-Probe can detect NaOCl and exhibits maximum fluorescence in the pH range of 7 to 8, similar to physiological conditions. ESI-MS analysis and 1H NMR spectroscopy titrations showed the formation of sulfoxide as the major oxidized product upon addition of hypochlorite. More interestingly, when WS-Probe was treated with real water samples, the fluorescence response was clearly visible with tap water and disinfectant, which indicated the presence of OCl? in these samples. The in vitro cell viability assay performed with human embryonic kidney 293 (HEK 293) cells suggested that WS-probe is non-toxic up to 10 μm and implicates the use of the probe for biological applications.

One-Photon Excitation Followed by a Three-Step Sequential Energy–Energy–Electron Transfer Leading to a Charge-Separated State in a Supramolecular Tetrad Featuring Benzothiazole–Boron-Dipyrromethene–Zinc Porphyrin–C60

A panchromatic triad, consisting of benzothiazole (BTZ) and BF2-chelated boron-dipyrromethene (BODIPY) moieties covalently linked to a zinc porphyrin (ZnP) core, has been synthesized and systematically characterized by using 1H NMR s

BORON-CONTAINING CYCLIC EMISSIVE COMPOUNDS AND COLOR CONVERSION FILM CONTAINING THE SAME

The present disclosure relates to novel photoluminescent complex comprising a BODIPY moiety covalently bonded to a blue light absorbing moiety, and a color conversion film, a back-light unit using the same.

IMPROVED WAVELENGTH CONVERSION FILM

Described herein is an improved wavelength conversion film with composite materials that have improved quantum efficiency and color gamut. The film includes narrow FWHM green and red emitting dyes.

Novel enzymatic reduction of α-amido- and α-cyanoalkyl-β-keto esters catalyzed by ketoreductases

An enzymatic approach for the asymmetric reduction of α-amido- and α-cyanoalkyl-β-keto esters has been developed. We have shown that NADPH-dependent ketoreductases can catalyze these transformations with excellent activity and high stereoselectivity, leading to optically pure β-hydroxy-α-amido esters as well as optically pure β-hydroxy-α-cyanoalkyl esters. With this method tert-butyl 2-acetamido-3-hydroxy-4-methylpentanoate, a valuable chiral intermediate for the synthesis of lactacystin, was obtained in high yield and excellent anti-diastereoselectivity. The ketoreductase catalyzed reduction of α-cyanomethyl- and α-cyanoethyl-β-keto esters to form the corresponding optically pure β-hydroxy esters, which are chiral intermediates for the synthesis of optically pure α-substituted γ-butyro and δ-valerolactams, was accomplished in high yield and high stereoselectivity leading to one stereoisomer out of four (>99 % de, >99 % ee, >99 % conversion).