761440-16-8

Basic information

• Product Name: 2,5-dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine
• Synonyms: (2,5-Dichloropyrimidin-4-yl)[2-[(propan-2-yl)sulfonyl]phenyl]amine; 4-Pyrimidinamine, 2,5-dichloro-N-[2-[(1-methylethyl)sulfonyl]phenyl]-; (2,5-Dichloropyrimidin-4-yl)[2-(propane-2-sulfonyl)phenyl]-amine; 2,5-Dichloro-N-[2-[(1-methylethyl)sulfonyl]phenyl]-4-pyrimidinamine; 2,5-Dichloro-N-[2-(propane-1-sulfonyl)phenyl]pyrimidin-4-amine; (2,5-Dichloro-pyrimidin-4-yl)-[2-(propane-1-sulfony)-phenyl]-amine; 2,5-Dichloro-N-(2-(iso-propylsulfonyl)phenyl)-pyrimidin-4-amine; 2,5-Dichloro-N-(2-(isopropylsulfonyl)-phenyl)pyrimidin-4-amine; 2,5-Dichloro-N-[2-(isopropylsulfonyl)phenyl]pyrimidin-4-amine; 2,5-dichloro-n-(2-((1-methylethyl)sulfonyl)phenyl)-4-pyrimidinamine; 2,5-dichloro-N-(2-(isopropyl sulfonyl)phenyl)-pyrimidine-4-amine
• CAS NO: 761440-16-8
• Molecular Formula: C₁₃H₁₃Cl₂N₃O₂S
• Molecular Weight: 346.23112
• Mol File: 761440-16-8.mol

Chemical Properties

• Melting Point: 149.0 to 153.0 °C
• Boiling Point: 538℃
• Flash Point: 279℃
• Appearance: /
• Density: 1.436
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• PKA: -0.03±0.10(Predicted)
• CAS DataBase Reference: 2,5-dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine(CAS DataBase Reference)
• NIST Chemistry Reference: 2,5-dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine(761440-16-8)
• EPA Substance Registry System: 2,5-dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine(761440-16-8)

Safety Data

• Hazardous Substances Data: 761440-16-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2,5-dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine is used as a reagent for the synthesis of ALK-5 inhibitors, which are employed as anti-tumor treatments. 2,5-dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine plays a significant role in the development of targeted therapies for cancer, specifically for malignancies where the ALK-5 enzyme is implicated.

InChI:InChI=1S/C13H13Cl2N3O2S/c1-8(2)21(19,20)11-6-4-3-5-10(11)17-12-9(14)7-16-13(15)18-12/h3-8H,1-2H3,(H,16,17,18)

Upstream product

• 1493-27-2 ortho-nitrofluorobenzene 
• 76697-50-2 1-amino-2-(isopropylsulphonyl)benzene 
• 5750-76-5 2,4,5-trichloropyrimidine 
• 70415-85-9 2-(isopropyl sulfanyl)nitrobenzene 
• 70415-86-0 1-(isopropylsulfonyl)-2-nitrobenzene 
• 6397-33-7 2-aminophenyl isopropyl sulphide 
• 137-07-5 2-amino-benzenethiol 
• 1632485-14-3 2,5-dichloro-N-[2-(propan-2-ylsulfanyl)phenyl]pyrimidin-4-amine 
• 861343-73-9 2-(isopropylthioether)aniline hydrochloride 
• 88-73-3 2-Chloronitrobenzene 
• 98-95-3 nitrobenzene 
• 1401466-33-8 4-bromo-2,5-dichloropyrimidine 
• 1780-31-0 2,6-dichloro-5-methylpyrimidine 

Downstream Products

• 1035230-15-9 C₃₄H₄₃ClN₆O₆S 
• 1032900-23-4 5-chloro-N₂-(2-isopropoxy-5-methyl-4-morpholin-4-ylmethyl-phenyl)-N₄-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine 
• 1032903-64-2 4-(4-{5-chloro-4-[2-(propane-2-sulfonyl)phenylamino]pyrimidin-2-ylamino}-5-isopropoxy-2-methylphenyl)piperidine-1-carboxylic acid tert-butyl ester 
• 1346447-76-4 5-chloro-N₄-(2-(isopropylsulfonyl)phenyl)-N₂-(3-nitrobenzyl)pyrimidine-2,4-diamine 
• 1346447-79-7 5-chloro-N⁴-(2-(isopropylsulfonyl)phenyl)-N²-(3-nitrophenyl)pyrimidine-2,4-diamine 
• 1346447-77-5 N₂-(3-aminobenzyl)-5-chloro-N₄-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine 
• 1346447-78-6 N-(3-(((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)methyl)phenyl)acrylamide 
• 1346447-80-0 5-chloro-4-N-(2-isopropylsulfonylbenzene)-2-N-(3-aminophenyl)pyrimidine-2,4-diamine 
• 1346447-81-1 N-(3-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)phenyl)acrylamide 
• 1346447-86-6 N₂-(5-amino-2-methoxybenzyl)-5-chloro-N₄-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine 
• 1346447-87-7 N-(3-(((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)methyl)-4-methoxyphenyl)acrylamide 
• 1346447-85-5 5-chloro-N₄-(2-(isopropylsulfonyl)phenyl)-N₂-(2-methoxy-5-nitrobenzyl)pyrimidine-2,4-diamine 
• 1190399-47-3 1-(4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-1-yl)-2-(dimethylamino)ethanone 
• 1609170-60-6 (R)-5-chloro-N-2-(2,5-dimethyl-4-(piperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-N-4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine 

Relevant articles and documents

Discovery of novel mutant-combating ALK and ROS1 dual inhibitors bearing imidazolidin-2-one moiety with reasonable PK properties

Aiming to identify novel potent ALK and ROS1 dual inhibitors, the relatively bulky piperidine fragment in ceritinib was replaced with substituted imidazolidin-2-one moiety which gave rise to a series of 2,4-diaryl-aminopyrimidine (DAAP) analogs (6–33). SAR studies were conducted based on cellular assays on five cell lines and most compounds exerted moderated to excellent activities. Among them, 15 showed excellent inhibitory activities against ROS1 and ALK positive cell lines, especially Ba/F3G1202R, with IC50 values ranging from 14 to 37 nM. As a continuation, several compounds were tested in enzymatic assays and 15 displayed encouraging activities against wild-type ALK (1.2 nM), ROS1(0.43 nM) as well as extremely resistant ALKL1196M and ALKG1202R mutants with IC50 values of 0.73 nM and 6.7 nM, respectively. To our delight, both cellular and enzymatic results of 15 were in good accordance with western blot assays on H2228 and HCC78 cell lines. Importantly, pharmacokinetic (PK) profiles of 15 were obtained with quite satisfying AUC and Cmax values. Besides, the binding models of 15 with ALKWT, ALKG1202R and ROS1 clearly present the essential interactions within the active site.

CHEMICAL PROCESS FOR PREPARING PYRIMIDINE DERIVATIVES AND INTERMEDIATES THEREOF

PROBLEM TO BE SOLVED: To provide a process for preparing ceritinib and/or intermediates thereof. SOLUTION: There is provided a process for preparing (C2-1), an intermediate of ceritinib synthesis, comprising the step of reacting (A) with (B) in a solvent in the presence of at least one catalyst, wherein P is a protecting group and T and X1 independently denote Cl and the like. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT

CDK inhibitor based on organic arsine as well as preparation method and application of CDK inhibitor

The invention provides a CDK inhibitor based on organic arsine as well as a preparation method and application of the CDK inhibitor. Specifically, the invention providese compounds of Formula I, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts, hydrates or solvates thereof; and the invention also discloses a preparation method and application thereof. Definitions of allgroups in the formula are shown in the specification.

Small molecule inhibitors of leucine-rich repetitive kinase 2 and their applications

The present invention provides a small molecule inhibitor of leucine-rich repetitive kinase 2 and applications thereof; compounds as small molecule inhibitors such as compounds shown in formula I of the present invention or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, hydrates, prodrugs and polymorphs. The compound has a high LRRK2 inhibitory activity and has high application value in the preparation of drugs for the treatment of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and other diseases.

POTENT AND SELECTIVE DEGRADERS OF ALK

Disclosed are bispecific compounds (degraders) that target ALK or ALK and FAK for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the bispecific compounds to treat diseases and disorders characterized or mediated by aberrant ALK or ALK and FAK activity.

Ceritinib intermediate and preparation method thereof

The invention discloses a ceritinib intermediate and a preparation method thereof. The preparation method of the ceritinib intermediate comprises the following steps: (1) under anhydrous oxygen-free conditions, in a polar aprotic solvent and under conditions of a metal hydride, performing a N-arylation reaction on an intermediate V and an intermediate IV to obtain an intermediate III; (2) in a solvent and under an acidic condition, hydrolyzing the intermediate III to obtain an intermediate II; and (3) in a solvent, performing a chlorination reaction on the intermediate II to obtain the ceritinib intermediate. The raw materials used in the preparation method provided by the invention are safe and non-toxic, reactions are simple and easy to operate, side reactions are few, water is adopted for post-treatment and even crystallization, thus production costs are reduced, the prepared product has high purity, and the ceritinib intermediate is easy for industrialized production.

Chemical Process for Preparing Pyrimidine Derivatives and Intermediates Thereof

The present disclosure relates to a method of synthesizing 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine (ceritinib) and/or intermediates thereof, their use as pharmaceuticals and pharmaceutical compositions and the use of intermediates for preparing ceritinib.

Preparation method of ceritinib

The invention relates to the field of medicinal chemistry, in particular to a preparation method of Ceritinib. According to the method, 2,5-dichloro-N-(2-(isopropylthio)phenyl)pyrimidine-4-amine is used as a raw material, and compared with the prior art, when the cefacitinib is prepared, impurities are reduced, the condition that impurities in a final product cefacitinib bulk drug exceed the standard is avoided, aftertreatment is simple, the refining frequency is small, and the reaction yield is increased.

Fragment-based modification of 2,4-diarylaminopyrimidine derivatives as ALK and ROS1 dual inhibitors to overcome secondary mutants

In order to explore novel ALK and ROS1 dual inhibitors capable of overcoming crizotinib-resistant mutants, two series of 2,4-diarylaminopyrimidine derivatives were designed, synthesized and evaluated for their in vitro cytotoxic activity. In this work, we retained the 2,4-diarylaminopyrimidine scaffold and derivatize the DAAP scaffold with sulfonyl and acrylamide moieties to extend the structure–activity relationship (SAR) study. To our delight, some compounds exhibited excellent inhibitory activity with a double-digit nanomolar level in MTT assay. Four compounds were selected for enzymic assays further, the results led to the identification of a potent ALK and ROS1 dual inhibitor X-17, with IC50 values of 3.7 nM, 2.3 nM, 8.9 nM and 1.9 nM against ALK, ALKL1196M, ALKG1202R and ROS1, respectively. Ultimately, the molecular docking studies on X-17 clearly disclosed reasonable and optimal binding interactions with ALK.

2, 4, 5-substituted pyrimidine compound and preparation method and application thereof

The invention relates to a preparation method of 2, 4-substituted pyrimidine compound and a preparation method and application thereof. The compound has a molecular structure shown as a formula I or pharmaceutically acceptable salt, solvate, stereoisomer or prodrug molecule thereof. The 2, 4, 5-substituted pyrimidine compound is low in cytotoxicity and has high selective inhibition on EGFR; the compound can inhibit the proliferation of EGFR drug-resistant mutant enzymes (such as T790M/L858R/C797S mutant enzymes) and cell strains thereof at a low concentration (such as nanomole concentration),so that the compound can be used for treating diseases caused by EGFR mutation, and is expected to be developed into a new generation of EGFR inhibitors.