cas 76697-50-2, 1-AMINO-2-(ISOPROPYLSULPHONYL)BENZENE

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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.
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Paragraph 0412-0414; 0421-0423

(2021/03/31)

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
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Paragraph 0174-0175; 0176

(2021/05/21)

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.
Chen, Yuxiang,Guo, Ming,Li, Tong,Li, Wei,Wei, Shangfei,Zhai, Xin,Zhao, Tianming,Zhu, Minglin
(2020/09/01)

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.
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Paragraph 0281; 0283

(2020/02/20)

CHEMICAL PROCESS FOR PREPARING PYRIMIDINE DERIVATIVES AND INTERMEDIATES THEREOF
PROBLEM TO BE SOLVED: To provide a method for producing intermediates for preparing ceritinib. SOLUTION: There is provided a method for preparing (C2-1), comprising 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 can be independently C1 and the like. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
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Paragraph 0175; 0176

(2020/01/09)

Focal adhesion kinase inhibitor and use
The invention belongs to the field of medicines, relates to a focal adhesion kinase inhibitor and use, in particular relates to a novel focal adhesion kinase inhibitor compound, or stereoisomers, geometric isomers, tautomers, oxynitrides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof, further relates to the use of the compound and pharmaceutical compositions as medicines, in particular the use of the compound and pharmaceutical compositions in manufacture of medicines for treatment or prevention of cancer, pulmonary hypertension, and pathological angiogenesis-related diseases.
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Paragraph 0631; 0633; 0634

(2019/01/08)

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.
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Paragraph 0260; 0262

(2018/03/25)

2,4-diarylaminopyrimidine derivative as well as preparation method and application thereof
The invention relates to a 2,4-diarylaminopyrimidine derivative shown as a general formula I and optical isomers thereof, pharmaceutically acceptable salts, solvates or prodrugs, as well as preparation methods thereof and a pharmaceutical composition taking the compound of the general formula I as an active ingredient. In the formula, substituent groups R1, R2, R3, R4, R5, R6 and X have meanings given in the description. The invention further relates to a compound of the general formula I with strong ALK and ROS1 kinase inhibition effects, and further relates to application of the compounds and optical isomers and pharmaceutically acceptable salts thereof in preparation of medicines for treating and/or preventing diseases caused by abnormal expressions of ALK and ROS1, particularly application in preparation of medicines for treating and/or preventing cancers. The structural formula is as shown in the description.
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Paragraph 0203; 0204

(2018/07/03)

A Class of Amide Ligands Enable Cu-Catalyzed Coupling of (Hetero)aryl Halides with Sulfinic Acid Salts under Mild Conditions
The amide derived from 4-hydroxy-l-proline and 2,6-dimethylaniline is a powerful ligand for Cu-catalyzed coupling of (hetero)aryl halides with sulfinic acid salts, allowing the formation of a wide range of (hetero)aryl sulfones from the corresponding (hetero)aryl halides at considerably low catalytic loadings. The coupling of (hetero)aryl iodides and sodium methanesulfinate proceeds at room temperature with only 0.5 mol % CuI and ligand, representing the first example for Cu-catalyzed arylation at both low catalytic loading and room temperature.
Zhao, Jinlong,Niu, Songtao,Jiang, Xi,Jiang, Yongwen,Zhang, Xiaojing,Sun, Tiemin,Ma, Dawei
p. 6589 - 6599
(2018/05/31)

Preparation method for ceritinib and intermediate thereof
The invention provides a preparation method for ceritinib and an intermediate thereof. The method comprises the following steps: (1) coupling the compound 1-dihydrochloride with the compound 2,5-dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine (a compound 3) so as to produce 5-chloro-N2-(2-isopropanolato-5-methyl-4-(piperid-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine dihydrochloride (a compound 4, i.e., ceritinib dihydrochloride); and (2) subjecting the compound 4 to dissociation so as to produce ceritinib. The preparation method provided by the invention is low in cost and high in yield, and the purity of the intermediate in each step is 99.5% or above, so high purity of ceritinib is guaranteed. The method is few in steps, simple to operate and suitable for industrial production and has great application value.
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Paragraph 0064

(2017/07/22)

4-Saturated cyclosubstituted aniline protein kinase inhibitor
The invention discloses a compound being able to adjust the activity of protein kinase and used for treating or preventing protein kinase related diseases, concretely relates to a 4-saturated cyclosubstituted aniline protein kinase inhibitor belonging to a compound for adjusting the activity of anaplastic lymphoma kinase (ALK), and provides a preparation method of the compound and a pharmaceutical use of the compound in treatment or prevention of ALK related diseases.
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Paragraph 0099; 0141; 0142; 0143

(2017/04/29)

Including zong pyrimidine derivative and use thereof (by machine translation)
The invention relates to the general formulaIThe pyrimidine derivatives including zong shown and its optical isomer, pharmaceutically acceptable salt, solvate or prodrug, their preparation method and as shown in the formula I compound as an active ingredient of the pharmaceutical composition, wherein the substituents R1 , R2 , R3 , Ar, X has the meanings given in the specification. The invention also relates to the compounds of the general formula I has strong ALK and ROS1 kinase inhibitory activity, and also relates to the compounds and its optical isomer, a pharmaceutically acceptable salt thereof for the treatment and/or the prevention of the ROS1 ALK and of diseases caused by the abnormal expression of the pharmaceutical in the application, in particular in preparing and treating and/or preventing cancer of the use of the medicament. (by machine translation)
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Paragraph 0119; 0120

(2017/09/21)

A method for preparing color Switzerland for Nepal
The invention discloses a method for preparing ceritinib, belonging to the field of chemical pharmacy. The method comprises the following steps: by taking 3-bromine-4-methylphenol as an initial raw material, performing phenolic hydroxyl isopropylation, nitration, coupling and reduction reaction, obtaining a midbody 1, by further taking o-nitro fluorobenzene as another initial raw material, performing isosulfhydrylation, oxidation, reduction and pyrimidine, obtaining a midbody 2, performing coupling reduction on the midbody 1 and the midbody 1, obtaining ceritinib which is protected by BOC acid anhydride, and finally removing a t-butyloxycarboryl protecting group, and obtaining ceritinib. The method is simple and feasible to operate, relatively high in yield, small in pollution and applicable to industrial production.
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Paragraph 0029; 0030

(2017/08/25)

Pyridone protein kinase inhibitor
The invention discloses a compound capable of regulating protein kinase activity and used for treating or preventing diseases related to protein kinase, particularly relates to a pyridone protein kinase inhibitor, belongs to compounds for regulating anaplastic lymphoma kinase (ALK) activity, and provides a preparation method of the compounds and pharmaceutical application of the compounds to the treatment or prevention of the diseases related to ALK.
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Paragraph 0088; 0101; 0102

(2017/04/19)

PROCESS FOR PREPARATION OF CERITINIB
The present application relates to a process for preparation of ceritinib and intermediates thereof. Specifically, the present application relates to a process for preparation of N-(4-(1-benzyl- 1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)acetamide (VC) comprising treating N-(4-(bromomethyl)-2-isopropoxy-5-methylphenyl)acetamide (IIID) with 1- benzylpiperidin-4-one (IVA). The present application also relates to a process for conversion of N-(4-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-acetamide (VC) to ceritinib or an acid-addition salt thereof.
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Page/Page column 42

(2016/12/26)

Anti-cancer drug ceritinib intermediate 1-amino-2-(isopropyl sulfonyl)benzene synthetic method
The invention belongs to the technical field of medicine synthesis, and especially relates to a synthetic method of an anti-cancer drug ceritinib intermediate 1-amino-2-(isopropyl sulfonyl)benzene. The synthetic method comprises the following steps: employing o-fluoronitrobenzene, sodium hydride and isopropyl mercaptan to synthesize a 2-(isopropyl sulfide) nitrobenzene crude product, then directly reducing the crude product to iron powder, forming salt to obtain the 2-(isopropyl sulfide) aniline hydrochloride, and finally dropping hydrogen peroxide for oxidation in 2-(isopropyl sulfide) aniline hydrochloride for oxidation, forming salt, and dissociating to obtain a target product. The synthetic method has the advantages of simpleness, little sewage amount, low energy consumption, low production cost, and the product has the advantages of high purity, high yield, and easy industrial production, and is suitable for further popularization and application.
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Page/Page column 0033-0041

(2017/07/21)

Design, synthesis and biological evaluation of novel 4-arylaminopyrimidine derivatives possessing a hydrazone moiety as dual inhibitors of L1196M ALK and ROS1
A series of 4-arylaminopyrimidine derivatives possessing a hydrazone moiety were designed, synthesized and evaluated for their biological activity. Most compounds exhibited moderate to excellent cytotoxic activity against ALK-addicted KARPAS299 and ROS1-addicted HCC78, while also showing much less potent activity against A549, H460 and HT-29, whose growth were not dependent on ALK and/or ROS1, as compared with crizotinib and ceritinib. The most promising compound, 7b, showed high antiproliferative effects on ALK-addicted KARPAS299 and ROS1-addicted HCC78?cell lines with IC50of 20?nM and 28?nM, respectively, but showed no inhibitory activity against A549, H460 and HT-29. The enzymatic assay identified 7b as a potent and selective ALK and ROS1 dual inhibitor with IC50of 2.5?nM and 2.7?nM, respectively. It also exhibited good inhibitory activity against the L1196M ALK with an IC50value of 67?nM.
Wang, Yu,Zhang, Guogang,Hu, Gang,Bu, Yanxin,Lei, Hongrui,Zuo, Daiying,Han, Mengting,Zhai, Xin,Gong, Ping
p. 80 - 89
(2016/08/01)

METHODS OF CHEMOTYPE EVOLUTION
Herein is described a method to rapidly screen a large chemical space for a compound that binds to a target protein through an iterative fragment assembly approach that can be performed at low reagent cost and without requiring purification of the assembled product. The method employs a library of test ligands each of which comprise a ‘bait’ molecule, which is known from prior art or prior screening to have some intrinsic affinity for the target protein, and a test moiety.
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Paragraph 0221; 0224

(2015/11/10)

CERTAIN PROTEIN KINASE INHIBITORS
Disclosed herein are protein kinase inhibitors, more particu-larly novel pyrimidine derivatives and pharmaceutical com-positions thereof, and method of use thereof
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Paragraph 0626; 0627

(2014/05/20)

COMPOUNDS THAT MODULATE EGFR ACTIVITY AND METHODS FOR TREATING OR PREVENTING CONDITIONS THEREWITH
Provided are compounds and methods for treating or preventing kinase-mediated disorders therewith.
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Page/Page column 46-47

(2011/11/30)

149. Notizen zur Synthese von 2-Aminophenylsulfonen
Syntheses of the alkyl, cycloalkyl and aryl 2-aminophenyl sulfones 10 were achieved by oxidation of the corresponding 2-nitrophenyl sulfides 7 to the 2-nitrophenyl sulfones 9 followed by ethanolic Bechamp-reduction.The sulfides 7 in turn were obtained by either reactions of 2-nitro-thiophenol (8) with the appropriate alkyl and cycloalkyl halides or of 2-chloro-nitrobenzene (5) with the relevant thiols.Condensation of 2-nitrobenzenesulfinic acid (3) with bromoacetic acid in aqueous alkaline solution led - presumably via 2-nitrophenylsulfonylacetic acid (4) - to methyl2-nitrophenyl sulfone (1), reduction of which gave 2-aminophenyl methyl sulfone (2).Treatment of 2-aminothiophenol (11) with t-butyl alcohol in aqueous sulfuric acid gave 2-aminophenyl t-butyl sulfide (12), which was acetylated to o-t-butylthio-acetanilide (13).Oxidation of the latter to o-t-butylsulfonyl-acetanilide (14) followed by hydrolysis led to 2-aminophenyl t-butyl sulfone (15).
Courtin, Alfred,Tobel, Hans-Rudolf von,Auerbach, Guenther
p. 1412 - 1419
(2007/10/02)