214470-68-5

Basic information

• Product Name: 4-CHLORO-7-(3-CHLORO-PROPOXY)-6-METHOXY-QUINOLINE-3-CARBONITRILE
• Synonyms: 4-CHLORO-7-(3-CHLORO-PROPOXY)-6-METHOXY-QUINOLINE-3-CARBONITRILE;4-Chloro-7-(3-chloropropoxy)-3-cyano-6-methoxyquinoline;4-Chloro-7-(3-chloropropoxy)-3-cyano-6-methyloxyquinoline;4-Chloro-7-(3-chloropropoxy)-6-methoxy-3-quinolinecarbonitrile;7-(3-chloro-propoxy)-4-chloro-6-Methoxy-quinoline-3-carbonitrile;3-Quinolinecarbonitrile, 4-chloro-7-(3-chloropropoxy)-6-Methoxy-
• CAS NO: 214470-68-5
• Molecular Formula: C₁₄H₁₂Cl₂N₂O₂
• Molecular Weight: 311.16328
• EINECS: 1592732-453-0
• Product Categories: Intermediates
• Mol File: 214470-68-5.mol

Chemical Properties

• Boiling Point: 478.1°C at 760 mmHg
• Flash Point: 243°C
• Appearance: /
• Density: 1.37
• Vapor Pressure: 2.64E-09mmHg at 25°C
• Refractive Index: 1.607
• Storage Temp.: Inert atmosphere,Room Temperature
• PKA: 0.57±0.41(Predicted)
• CAS DataBase Reference: 4-CHLORO-7-(3-CHLORO-PROPOXY)-6-METHOXY-QUINOLINE-3-CARBONITRILE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-CHLORO-7-(3-CHLORO-PROPOXY)-6-METHOXY-QUINOLINE-3-CARBONITRILE(214470-68-5)
• EPA Substance Registry System: 4-CHLORO-7-(3-CHLORO-PROPOXY)-6-METHOXY-QUINOLINE-3-CARBONITRILE(214470-68-5)

Safety Data

• Hazardous Substances Data: 214470-68-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-Chloro-7-(3-chloropropoxy)-6-methoxy-quinoline-3-carbonitrile is used as a chemical intermediate for the green preparation of the anti-tumor medication Bosutinib (B676095). 4-CHLORO-7-(3-CHLORO-PROPOXY)-6-METHOXY-QUINOLINE-3-CARBONITRILE plays a crucial role in the synthesis of Bosutinib, a targeted cancer therapy drug that inhibits the activity of certain enzymes involved in the development of cancer cells.
The application of 4-Chloro-7-(3-chloropropoxy)-6-methoxy-quinoline-3-carbonitrile in the pharmaceutical industry is primarily due to its utility in the production of Bosutinib, which is a valuable anti-cancer agent. Bosutinib is particularly effective against various types of cancer, including leukemia, and has been shown to improve patient outcomes when used in combination with other treatments. The use of this intermediate in the green synthesis process also highlights its importance in developing more environmentally friendly and sustainable methods for producing life-saving medications.

InChI:InChI=1/C14H12Cl2N2O2/c1-19-12-5-10-11(6-13(12)20-4-2-3-15)18-8-9(7-17)14(10)16/h5-6,8H,2-4H2,1H3

Upstream product

• 627-30-5 1-chloro-3-hydroxypropane 
• 263149-10-6 4-chloro-7-hydroxy-6-methoxyquinolin-3-carbonitrile 
• 214470-66-3 7-(3-chloropropoxy)-6-methoxy-4-oxo-1,4-dihydroquinoline-3-carbonitrile 
• 3943-74-6 4-hydroxy-3-methoxybenzoic acid methyl ester 
• 3535-27-1 methyl 4-isopropoxy-3-methoxybenzoate 
• 948553-02-4 4-isopropoxy-5-methoxy-2-nitro-benzoic acid methyl ester 
• 741276-43-7 7-isopropyloxy-6-methoxy-4-chloroquinoline-3-carbonitrile 
• 214470-59-4 2-Amino-4-(3-chloro-propoxy)-5-methoxy-benzoic acid methyl ester 
• 109-70-6 1.3-chlorobromopropane 
• 6940-76-7 1-iodo-3-chloro-propane 
• 1637593-19-1 3-(2-amino-4-(3-chloropropoxy)-5-methoxyphenyl)-3-oxopropanenitrile 
• 1637593-18-0 3-(4-(3-chloropropoxy)-5-methoxy-2-nitrophenyl)-3-oxopropanenitrile 
• 1160707-44-7 1-[4-(3-chloropropoxy)-5-methoxy-2-nitrophenyl]ethan-1-one 
• 58113-30-7 4-(3-chloropropoxy)-3-methoxyacetophenone 

Downstream Products

• 331662-94-3 7-(3-chloropropoxy)-4-[(2,4-dichlorophenyl)amino]-6-methoxy-3-quinolinecarbonitrile 
• 380844-49-5 7-(3-chloropropoxy)-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile 
• 863029-97-4 4-{3-chloro-4-[(1-methyl-1H-imidazole-2-yl)sulfanyl]anilino}-7-(3-chloropropoxy)-6-methoxy-3-quinolinecarbonitrile 
• 380843-81-2 4-((2,4-dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(piperazin-1-yl)propoxy)quinoline-3-carbonitrile 
• 380843-75-4 bosutinib 

Relevant articles and documents

Bosutinib purification method

The invention provides a bosutinib purification method. The method includes the steps of firstly, dissolving crude bosutinib in an acetonitrile-water mixed solvent; secondly, optionally performing activated carbon decoloring, and filtering to obtain filtrate; thirdly, cooling, crystallizing, filtering, and drying to obtain purified bosutinib. The bosutinib purification method has the advantages that the method can replace a column chromatography purification method or a preparative chromatography purification method to remove impurities, which is hard to purify by a conventional crystallizingmethod, in the crude bosutinib, and the method is low in solvent use amount, simple in process, high in purification yield and product purity and beneficial to industrial production.

NOVEL CRYSTALLINE POLYMORPHS OF 4-[(2.4-DICHIORO-5-METHOXVPHENVL)ANIINOL- 6-METHOXV-7-13-(4-METHYL-L-PIPERAZINVL)PROPOXVL-3-QUINOLINECARBONITRILE AND PROCESS FOR PREPARATION THEREOF

The present invention relates to novel crystalline polymorphs of 4-[(2,4-dichloro-5- methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-l-piperazinyl)propoxy]-3-quinoline carbonitrile represented by the following structural formula- 1 and process for preparation thereof.

A kind of deuterium generation 3-cyano-quinoline compound, a pharmaceutically acceptable composition, preparation method and its use

Disclosed in the invention are a deuterated 3-cyano quinoline compound or pharmaceutically acceptable salts, solvates, prodrugs, stereoisomers, tautomers, polymorphic substances, metabolites etc., and a pharmaceutical composition containing such compounds, and the use of these compounds or compositions in the preparation of drugs for treating or preventing tumours, especially drugs such as protein kinase inhibitors. Compared with the prior art, the compounds of the present invention have the clear advantages of properties such as plasma drug concentration, half-life, clearance, microsomal stability, bioavailability or enzyme inhibition and the like, and thus can more effectively inhibit the activities of more than one protein kinase and/or inhibit the growth of tumuor cells.

New Synthetic Process for Bosutinib

A new and improved synthetic route to bosutinib is described on a hectogram scale. The key step is the intramolecular cyclization of a 3-(2-aminophenyl)-3-oxopropanenitrile with N,N-dimethylformamide dimethyl acetal to form the 3-cyano-4-hydroxyquinoline ring of 7-(3-chloropropoxy)-6-methoxy-4-oxo-1,4-dihydroquinoline-3-carbonitrile. A practical synthetic method to 2,4-dichloro-5-methoxyaniline is also established. Bosutinib is obtained in 18.0% yield over nine steps from acetovanillone with 98.9% purity (HPLC).

A new and practical synthesis of bosutinib

New and improved synthetic route of bosutinib is described on a decagram scale. An intramolecular cyclization of 3-amino-2-(2-bromobenzoyl)-acrylonitrile (22) in K2CO3/DMF condition to form the key 3-cyano-4-hydroxyquinoline intermediate (13) is adopted as the key step. Bosutinib is obtained in 13.7% yield over ten steps and 98.9% purity (HPLC), which make it as a process of cost effective, environmentally friendly and feasible for scale-up operation.

Synthesis of bosutinib from 3-methoxy-4-hydroxybenzoic acid

This paper reports a novel synthesis of bosutinib starting from 3-methoxy-4-hydroxybenzoic acid. The process starts with esterification of the starting material, followed by alkylation, nitration, reduction, cyclization, chlorination and two successive amination reactions. The intermediates and target molecule were characterized by 1H-NMR, 13C-NMR, MS and the purities of all the compounds were determined by HPLC.

Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment

Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. Inhibitors of this receptor are believed to provide a new target in cancer therapy. We previously reported an isoquinolinedione series of IGF-1R inhibitors. Now we have identified a series of 3-cyanoquinoline compounds that are low nanomolar inhibitors of IGF-1R. The strategies, synthesis, and SAR behind the cyanoquinoline scaffold will be discussed.

3-Cyanoquinolines, Methods for Preparation and Use as Insulin-like Growth Factor Inhibitors

Imidazole-substituted 4-anilino-3-cyanoquinolines are described, which selectively inhibit IFGR kinase activity and are useful for treating disorders associated with IGFR kinases.

The design, synthesis and biological evaluation of 7-alkoxy-4-heteroarylamino-3-cyanoquinolines as dual inhibitors of c-Src and iNOS

Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heterocycle amine-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, synthesized and evaluated as multiple targets agents in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds inhibited c-Src and iNOS well. The best compound 8 inhibited both enzymes with the IC50 values of 34.8 nM and 26.7 μM. Several compounds also showed moderate anti-proliferation at 10 μM against colon and liver cancer cell lines.

Derivatives of quinoline as inhibitors for MEK

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof. wherein: n is 0-1; X and Y are independently selected from -NH-, -O-, -S-, or -NR8- where R8 is alkyl of 1-6 carbon atoms and X may additionally comprise a CH2 group; R7 is a group (CH2)mR9 where m is 0,or an integer of from 1-3 and R9 is a substituted aryl group, an optionally substituted cycloalkyl ring of up to 10 carbon atoms, or an optionally substituted heterocyclic ring or an N-oxide of any nitrogen containing ring; R6 is a divalent cycloalkyl of 3 to 7 carbon atoms, which may be optionally further substituted with one or more alkyl of 1 to 6 carbon atom groups; or is a divalent pyridinyl, pyimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally further substituted with one or more specified groups; R1, R2, R3 and R4 are each independently selected from hydrogen or various specified organic groups. Compounds are useful as pharmaceuticals for the inhibition of MEK activity.