6980-08-1

Basic information

• Product Name: 2-Amino-4-chloro-3-nitropyridine
• Synonyms: 2-AMINO-4-CHLORO-3-NITROPYRIDINE;4-Chloro-3-nitropyridin-2-amine;4-Chloro-3-nitro-pyridin-2-ylaMine;2-PyridinaMine, 4-chloro-3-nitro-
• CAS NO: 6980-08-1
• Molecular Formula: C₅H₄ClN₃O₂
• Molecular Weight: 173.56
• Product Categories: API intermediates;Nucleotides and Nucleosides;Bases & Related Reagents;Nucleotides;Pyridines;Amines;Aromatics;Heterocycles;Heterocycle-Pyridine series
• Mol File: 6980-08-1.mol

Chemical Properties

• Melting Point: 174-176°C
• Boiling Point: 329 °C at 760 mmHg
• Flash Point: 152.8 °C
• Appearance: /
• Density: 1.596 g/cm³
• Vapor Pressure: 0.000183mmHg at 25°C
• Refractive Index: 1.657
• Storage Temp.: -20°C Freezer
• Solubility: Soluble in dimethyl formamide, dimethyl sulfoxide, hot ethanol,
• PKA: 1.31±0.47(Predicted)
• CAS DataBase Reference: 2-Amino-4-chloro-3-nitropyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Amino-4-chloro-3-nitropyridine(6980-08-1)
• EPA Substance Registry System: 2-Amino-4-chloro-3-nitropyridine(6980-08-1)

Safety Data

• Hazardous Substances Data: 6980-08-1(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
2-Amino-4-chloro-3-nitropyridine is used as a key intermediate in organic synthesis for the production of various chemical compounds and materials. Its unique structure allows for a wide range of reactions and transformations, making it a valuable building block in the synthesis of complex organic molecules.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 2-Amino-4-chloro-3-nitropyridine is utilized as a starting material or intermediate in the development of pharmaceutically active compounds. It plays a crucial role in the synthesis of drugs targeting proliferative disorders and diseases where aurora kinase and/or FLT3 activity is implicated. Its involvement in the synthesis of 1-deaza-6-methylthiopurine ribonucleoside, a compound with cytotoxic properties, further highlights its potential in the development of therapeutic agents.
Used in Agrochemicals:
2-Amino-4-chloro-3-nitropyridine is also used as a raw material and intermediate in the agrochemical industry. Its unique chemical properties make it suitable for the development of agrochemical products, such as pesticides and herbicides, which can help protect crops and enhance agricultural productivity.
Used in Dyestuff Industry:
In the dyestuff industry, 2-Amino-4-chloro-3-nitropyridine serves as an important intermediate for the synthesis of various dyes and pigments. Its versatile chemical structure allows for the creation of a wide range of colorants, which can be used in various applications, such as textiles, plastics, and printing inks.
Overall, 2-Amino-4-chloro-3-nitropyridine is a multifaceted chemical intermediate with applications spanning across organic synthesis, pharmaceuticals, agrochemicals, and dyestuffs. Its unique structure and properties make it a valuable asset in the development of new and innovative products in these industries.

Reference

Tzvetkov, N. T.; Muller, C. E., Facile synthesis of 5-aminoand 7-amino-6-azaoxindole derivatives. Tetrahedron Lett. 2012, 53, 5597-5601. Julian Blagg; Bavetsias; Moore; Linardopoulos, pharmaceutically active compounds. US Patent US 9447092 B2 2016. JMontgomery, J. A.; Hewson, K., 1-DEAZA-6-METHYLTHIOPURINE RIBONUCLEOSIDE. J. Med. Chem. 1966, 9, 354-+. JHarry Louis Yale; Sheehan, J. T., CNS active compounds US Patent 4022897 1977.

InChI:InChI=1/C5H4ClN3O2/c6-3-1-2-8-5(7)4(3)9(10)11/h1-2H,(H2,7,8)

Upstream product

• 19798-80-2 2-Amino-4-chloropyridine 
• 24484-97-7 N-nitro-2-amino-4-chloropyridine 
• 13091-23-1 4-chloro-3-nitropyridine 

Downstream Products

• 942947-95-7 5-bromo-4-chloro-3-nitro-pyridin-2-ylamine 
• 662116-67-8 4,5-dichloro-3-nitropyridin-2-ylamine 
• 942948-56-3 5-chloro-4-(4-(4-chlorobenzyl)piperazin-1-yl)-3-nitropyridin-2-amine 
• 1402709-93-6 CCT₂₄₁₇₃₆ 
• 84487-08-1 4-methoxy-3-nitro-pyridin-2-ylamine 
• 1426833-19-3 1-(2,6-bismethyl-phenyl)-6-methoxy-4-methyl-2,3,5,9,9b-pentaazacyclopenta[a]naphthalene 
• 1426833-18-2 1-(2-chloro-6-methyl-phenyl)-6-methoxy-4-methyl-2,3,5,9,9b-pentaazacyclopenta[a]naphthalene 
• 1426824-69-2 N-[1-(2-chloro-phenyl)-methylidene]-N'-(8-methoxy-2-methyl-pyrido[2,3-b]pyrazin-3-yl)-hydrazine 

Relevant articles and documents

Design, synthesis and biological evaluation of novel substituted purine isosters as EGFR kinase inhibitors, with promising pharmacokinetic profile and in vivo efficacy

Novel substituted purine isosters, were designed and synthesized as potential inhibitors of the Epidermal Growth Factor Receptor (EGFR). The compounds were rationally designed through bioisosteric replacement of the central quinazoline core of lapatinib, an approved drug that inhibits both EGFR and HER2, another important member of this family of receptors. The new target molecules were evaluated as inhibitors of receptor phosphorylation at the cellular level, for their direct inhibitory action on the intracellular receptor kinase domain and for their cytotoxicity against the non-small cell lung cancer cell line A549 and breast cancer HCC1954, cell lines which are associated with overexpression of EGFR and HER2, respectively. The most potent derivatives were further studied for their cellular uptake levels and in vivo pharmacokinetic properties. One compound (23)displayed a noteworthy pharmacokinetic profile, and higher intracellular accumulation in comparison to lapatinib in the A549 cells, possibly due to its higher lipophilicity. This lead compound (23)was assessed for its efficacy in an EGFR positive xenograft model, where it successfully inhibited tumor growth, with a similar efficacy with that of lapatinib and with minimal phenotypic toxicity.

A simple approach to multifunctionalized N1-alkylated 7-amino-6-azaoxindole derivatives using their in situ stabilized tautomer form

A simple approach for the synthesis of multifunctionalized N1-alkyl 7-amino-6-azaoxindole derivatives was developed and investigated. Formation of 5-amino- and 7-amino-6-aza-2-oxindoles 12a and 13a, respectively, was achieved using an intramolecular reductive cyclization as a key step. Subsequent alkylation of the pyrrole N1 atom in 12a led to the desired N1-alkylated compounds 22a–24 comprising different functionalities. Alkylation of 5-amino-substituted regioisomer 13a under the same conditions as used for 12a did not resulted in N1-alkylated products. To find a plausible explanation for the observed differences in reactivity, we investigated the possible tautomers of 12a and 13a and the distribution of their neutral and ionized forms in a gas phase. The relevant physicochemical properties of compounds 12a and 23 were determined.

IMIDAZOPYRIDINES AS INHIBITORS OF AURORA KINASE AND/OR FLT3

The present invention relates to compounds of formula I: wherein R1 and R2 are as defined herein, or a pharmaceutically acceptable salt or solvate thereof. The compounds of formula I are inhibitors of aurora kinase and/or FLT3. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which aurora kinase and/or FLT3 activity is implicated.

Facile synthesis of 5-amino- and 7-amino-6-azaoxindole derivatives

An efficient approach for the formation of 5-amino- and 7-amino-6-azaoxindole derivatives was developed. 2-Amino-4-chloro-3- nitropyridine (8), and its 5-nitro-substituted regioisomer (9), respectively, were obtained by reaction with ethyl malonate. The resulting 2-amino-3/5-nitropyridine derivatives substituted in the 4-position with malonic acid diethyl ester (10, 11) were subjected to reductive cyclization yielding 3-ethoxycarbonyl-6-azaoxindole derivatives 4a and 5a. Protection of the amino function was not required. Intermediates 10 and 11 could also be converted to the corresponding 4-acetic acid ethyl esters 12 and 13 by dealkoxycarbonylation with LiCl, and subsequently cyclized under reductive conditions yielding 3-unsubstituted 5-/7-aminooxazindoles.

Optimization of imidazo[4,5- b ]pyridine-based kinase inhibitors: Identification of a dual FLT3/aurora kinase inhibitor as an orally bioavailable preclinical development candidate for the treatment of acute myeloid leukemia

Optimization of the imidazo[4,5-b]pyridine-based series of Aurora kinase inhibitors led to the identification of 6-chloro-7-(4-(4-chlorobenzyl)piperazin- 1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine (27e), a potent inhibitor of Aurora kinases (Aurora-A Kd = 7.5 nM, Aurora-B K d = 48 nM), FLT3 kinase (Kd = 6.2 nM), and FLT3 mutants including FLT3-ITD (Kd = 38 nM) and FLT3(D835Y) (Kd = 14 nM). FLT3-ITD causes constitutive FLT3 kinase activation and is detected in 20-35% of adults and 15% of children with acute myeloid leukemia (AML), conferring a poor prognosis in both age groups. In an in vivo setting, 27e strongly inhibited the growth of a FLT3-ITD-positive AML human tumor xenograft (MV4-11) following oral administration, with in vivo biomarker modulation and plasma free drug exposures consistent with dual FLT3 and Aurora kinase inhibition. Compound 27e, an orally bioavailable dual FLT3 and Aurora kinase inhibitor, was selected as a preclinical development candidate for the treatment of human malignancies, in particular AML, in adults and children.

Synthesis and biological evaluation of piperazinyl heterocyclic antagonists of the gonadotropin releasing hormone (GnRH) receptor

Antagonism of the gonadotropin releasing hormone (GnRH) receptor has resulted in positive clinical results in reproductive tissue disorders such as endometriosis and prostate cancer. Following the recent discovery of orally active GnRH antagonists based on a 4-piperazinylbenzimidazole template, we sought to investigate the properties of heterocyclic isosteres of the benzimidazole template. We report here the synthesis and biological activity of eight novel scaffolds, including imidazopyridines, benzothiazoles and benzoxazoles. The 2-(4-tert-butylphenyl)-8-(piperazin-1-yl)imidazo[1,2-a]pyridine ring system was shown to have nanomolar binding potency at the human and rat GnRH receptors as well as functional antagonism in vitro. Additional structure-activity relationships within this series are reported along with a pharmacokinetic comparison to the benzimidazole-based lead molecule.

Regioselectivity of the Amination of Some 3-Nitropyridines by Liquid Ammonia / Potassium Permanganate

3-Nitropyridine and some of its derivatives are aminated in a liquid ammonia solution of potassium permanganate to the corresponding 2- and (or) 4- and (or) 6-amino compounds.Quantumchemical calculations for a few 3-nitropyridines suggest that the experimentally observed regioselectivity of the amination is controlled by Coulombic interaction. --- Key Words: Amination / Nitropyridines / Reactivity indices / Calculations, MNDO

Substituent Effects on the Isomer Ratios in the Rearrangement of Some 2- and 4-Nitraminopyridines

The preparation, and rearrangement in 92percent sulfuric acid, of 4-X-2-nitramino- (1), 2-X-4-nitramino- (2), and 6-X-2-nitramino-pyridines (3) is reported (X=H,Me,MeO,Br,Cl,CO2H).The product isomer ratios can be explained by differential electronic stabilization of the appropriate ? complexes for aromatic nitration and steric effects seem relatively unimportant.Deuteration had no effect on the product distribution

Kinetic Studies of the Mechanism of the Nitraminopyridine Rearrangement

Rate data are reported for the rearrangement, in 92percent sulfuric acid at 30 deg C, of a series of 4-X-2-nitraminopyridines (X=H, Me, Br, Cl, MeO, CO2H) and of 4-methyl-2-nitramino(3-D)-pyridine.Values of pKa for second protonation of the corresponding pyridin-2-amines were also measured and rate constants for nitration of the monoprotonated pyridinamines were thereby calculated.The results suggest that the rate-determining step occurs prior to formation of the appropriate 3- and 5-nitro ? complexes.The nature of this step is not clear, however, and a key role for the nitramine itself is not proven by the current evidence