444731-75-3

Basic information

• Product Name: N-(2-chloropyriMidin-4-yl)-N,2,3-triMethyl-2H-indazol-6-aMine
• Synonyms: N-(2-chloropyriMidin-4-yl)-N,2,3-triMethyl-2H-indazol-6-aMine;N-(2-chloro-4-pyriMidinyl)-N,2,3-triMethyl-2H-indazol-6-aMine;2H-Indazol-6-aMine, N-(2-chloro-4-pyriMidinyl)-N,2,3-triMethyl-;6-[N-(2-chloro-4-pyriMidinyl)MethylaMino]-2,3-diMethyl-2H-indazole, 96%;N-(2-ChloropyriMidin-4-yl)-N-Methyl-2,3-diMethyl-2H-indazol-6-aMine;N-(2-chloropyrimidin-4-yl)-N,2,3-trimethylindazol-6-amine;Pazopanib Impurity 8
• CAS NO: 444731-75-3
• Molecular Formula: C₁₄H₁₄ClN₅
• Molecular Weight: 288
• EINECS: 1592732-453-0
• Mol File: 444731-75-3.mol

Chemical Properties

• Melting Point: 167-173℃
• Boiling Point: 524.447 °C at 760 mmHg
• Flash Point: 270.976 °C
• Appearance: /
• Density: 1.339 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.673
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Very Slightly)
• PKA: 2.82±0.30(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: N-(2-chloropyriMidin-4-yl)-N,2,3-triMethyl-2H-indazol-6-aMine(CAS DataBase Reference)
• NIST Chemistry Reference: N-(2-chloropyriMidin-4-yl)-N,2,3-triMethyl-2H-indazol-6-aMine(444731-75-3)
• EPA Substance Registry System: N-(2-chloropyriMidin-4-yl)-N,2,3-triMethyl-2H-indazol-6-aMine(444731-75-3)

Safety Data

• Hazardous Substances Data: 444731-75-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
N-(2-chloropyrimidin-4-yl)-N,2,3-trimethyl-2H-indazol-6-amine is used as an impurity in the production of Pazopanib (P210925) for its role in targeting VEGFR and PDGFR. This application is crucial as it helps in the development and formulation of Pazopanib as an oral angiogenesis inhibitor, which is vital in the treatment of various types of cancer.
N-(2-chloropyriMidin-4-yl)-N,2,3-triMethyl-2H-indazol-6-aMine's presence as an impurity in Pazopanib highlights the importance of monitoring and controlling the quality and purity of active pharmaceutical ingredients. This ensures the safety and efficacy of the final drug product, which is essential for patients undergoing cancer treatment.

InChI:InChI=1/C14H14ClN5/c1-9-11-5-4-10(8-12(11)18-20(9)3)19(2)13-6-7-16-14(15)17-13/h4-8H,1-3H3

Upstream product

• 444731-74-2 N-(2-chloropyrimidin-4-yl)-2,3-dimethyl-2H-indazol-6-amine 
• 616-38-6 carbonic acid dimethyl ester 
• 7461-50-9 2-chloropyrimidin-4-amine 
• 1426675-40-2 6-chloro-2,3-dimethyl-2H-indazole 
• 74-88-4 methyl iodide 
• 1142189-49-8 6-bromo-2,3-dimethyl-1H-indazole 
• 90221-46-8 3-methyl-6-bromo-2H-indazole 
• 14922-91-9 2-ethyl-5-bromoaniline 
• 10342-66-2 4-bromo-1-ethyl-2-nitro-benzene 
• 612-22-6 2-nitro(ethylbenzene) 
• 635702-59-9 3-methyl-6-nitro-1H-indazole sulfate 
• 77-78-1 dimethyl sulfate 
• 1313372-75-6 3?methyl?6?nitro?1H?indazole 
• 578-54-1 ortho-ethylaniline 

Downstream Products

• 635702-64-6 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)-N-methylamino]-2-pyrimidinyl]amino]-2-methylbenzenesulfonamide hydrochloride 
• 635702-65-7 5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzenesulfonamide methanesulfonic acid salt 

Relevant articles and documents

Preparation method of pazopanib intermediate

The invention provides a preparation method of a pazopanib key intermediate 2,3-dimethyl-N-(2-chloropyrimidin-4-yl)-N-methyl-2H-indazole-6-amine. The method comprises the following steps: by taking 6-halogenated-2,3-dimethyl-2H-indazole as a raw material, conducting reacting to obtain N,2,3-trimethyl-2H-indazole-6-amine; and further carrying out a reaction to obtain the 2,3-dimethyl-N-(2-chloropyrimidin-4-yl)-N-methyl-2H-indazole-6-amine. The method has the advantages of short synthesis route, accessible raw materials, low cost, mild reaction conditions, high safety and high yield, and is suitable for industrial mass production.

A NOVEL PROCESS FOR PREPARATION OF PAZOPANIB HYDROCHLORIDE

The present invention relates to a new process for the preparation of a key intermediate compound and its use in a synthetic process for the preparation of pazopanib hydrochloride. The method has advantages of a simple operation, high yield and low costs. The present invention also relates to a novel polymorph of pazopanib hydrochloride.

Process-Related Impurities of Pazopanib

The main target of this study was to synthesize reference compounds for HPLC analysis of impurities, produced in Pazopanib synthesis. It is highly desirable that impurity standards are made available to help in developing an HPLC control method that could be suitable for use in the industrial process. To the best of our knowledge, most of these impurities are not commercially available and no synthetic methods have been reported. Potential impurities were synthesized, and their structures were established by various spectroscopy techniques.

Green preparation method of palatinib hydrochloride (by machine translation)

The invention belongs to the technical field of chemical synthesis of medicines, and belongs to the technical field of pharmaceutical chemistry. The invention particularly relates to a green preparation method. The o-methyl aniline and N - chlorosuccinimide are chlorinated to obtain 2 - methyl -5 - chloro- aniline; the 6 - chlorine - 222H-indole hydrochloride is obtained by reacting with the nitrous acid compound; N-methyl -6 -chloro - 222H-indole; under the participation of dimethyl sulfoxide, 3 - 2-dimethyl 3 - chlorine -6 - 222H-indazole; and the like. A reaction with 2 - chloro -4 - amino - pyrimidine and iodomethane gave N - (2 -chloropyrimidine -4 -yl) - N N-methyl -2, 3 -dimethyl - 222H-indazole -6 - amine; and finally, a pimatinib hydrochloride salt was obtained by reaction with 3 - sulfanilide -4 - methyl - aniline. The method is low in raw material price, simple to operate, low in operation risk, capable of avoiding waste acid generation, high in reaction yield, and high in purity. (by machine translation)

Synthesis and characterization of four process impurities in pazopanib

Pazopanib (trade name Votrient) is a potent and selective multi-targeted tyrosine kinase inhibitor that blocks tumor growth and inhibits angiogenesis. Based on a recently reported procedure, we herein report the first synthesis of four potential process impurities generated in the production of pazopanib. The structure of these impurities were synthesized and characterized by 1H NMR, 13C NMR and HRMS data. The possible formation mechanisms of these impurities were also elucidated. These findings should be useful for the quality control of pazopanib in manufacture.

Pazopanib structure based HDAC (histone deacetylase) and VEGFR (vascular endothelial growth factor receptor) dual-target inhibitor and preparation method and application thereof

The invention relates to a pazopanib structure based HDAC (histone deacetylase) and VEGFR (vascular endothelial growth factor receptor) dual-target inhibitor and a preparation method and application thereof. The compound has structures as are shown in formula I, formula II or formula III. The invention further provides a preparation method of the compounds and application of the compounds in preparing drugs for prevention or treatment of cancer-related diseases.

Discovery of Novel Pazopanib-Based HDAC and VEGFR Dual Inhibitors Targeting Cancer Epigenetics and Angiogenesis Simultaneously

Herein a novel series of pazopanib hybrids as polypharmacological antitumor agents were developed based on the crosstalk between histone deacetylases (HDACs) and vascular endothelial growth factor (VEGF) pathway. Among them, one ortho-aminoanilide 6d and one hydroxamic acid 13f exhibited considerable total HDACs and VEGFR-2 inhibitory activities. The HDAC inhibitory activities endowed 6d and 13f with potent antiproliferative activities, which was not observed in the approved VEGFR inhibitor pazopanib. Compounds 6d and 13f possessed comparable HDAC isoform selectivity profiles to the clinical class I HDAC inhibitor MS-275 and the approved pan-HDAC inhibitor SAHA, respectively. 6d and 13f also exhibited uncompromised multiple tyrosine kinases inhibitory activities relative to pazopanib. The intracellular dual inhibition to HDAC and VEGFR of 6d and 13f was validated by Western blot analysis. In both HUVECs tube formation assay and rat thoracic aorta rings assay, 6d and 13f showed comparable antiangiogenic potencies to pazopanib. What's more, 6d possessed desirable pharmacokinetic profiles with the oral bioavailability of 72% in SD rats and considerable in vivo antitumor efficacy in a human colorectal adenocarcinoma (HT-29) xenograft model.

AN IMPROVED PROCESS FOR THE PREPARATION OF PAZOPANIB OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF

The present invention is relates to an improved process for the preparation of pazopanib or a pharmaceutically acceptable salts thereof. The present invention also relates to novel polymorphic Forms of pazopanib hydrochloride, and its intermediates thereo

Hydrochloric acid [...] of the method for the preparation of intermediates

The invention discloses a preparation method of an intermediate (2,3-dimethyl-N-(2-chloropyrimidine-4-base)-N-methyl-2H-indazole-6-amine) of pazopanib hydrochloride as shown in a formula I. The preparation method comprises the step of performing nucleophilic substitution reaction on a compound III and 2,4-dichloropyrimidine in an organic solvent under the action of alkali, wherein the reaction temperature is 0-160 DEG C. According to the preparation method disclosed by the invention, raw materials are low in price and easy to obtain, and the preparation method is convenient to operate, high in product yield and suitable for industrial large-scale production.

PROCESS FOR THE PREPARATION OF PAZOPANIB OR SALTS THEREOF

The present invention provides a process for the preparation of pazopanib of Formula Ia or salts, and intermediates thereof.