- 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
- -
-
Paragraph 0168
(2021/05/21)
-
- Novel sulfinyl anilino pyrimidine derivative and application thereof in preparation of antitumor drugs
-
The invention relates to the field of medicines. A novel sulfinyl anilino pyrimidine derivative is disclosed, and the structural formula of the novel sulfinyl anilino pyrimidine derivative is as shown in the specification. Compared with an existing L858R/T790M inhibitor and EGFR / ALK double-target-target reference substance, the aniline-based pyrimidine derivative containing the sulfoxide group has better antitumor H 1975 activity compared with ALK the prior art BaF3 inhibitor and the EGFR/ALK double ALK-target reference substance. As proved by human liver microsomal experiments, the aniline-based pyrimidine derivatives containing the sulfoxide group in the invention are compared with the existing anisyl-containing anilino pyrimidine derivatives. There is a great increase in stability.
- -
-
-
- 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.
- -
-
Paragraph 0274-0275
(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
- -
-
Paragraph 0168; 0169
(2020/01/09)
-
- HYDRATE OF 2-ISOPROPOXY-5-METHYL-4-(PIPERIDIN-4-YL) ANILINE DIHYDROCHLORIDE, PREPARATION METHOD AND USE OF THE SAME
-
The present invention relates to 2-isopropoxy-5-methyl-4-(piperidin-4-yl) aniline dihydrochloride monohydrate and a preparation method of the same. The 2-isopropoxy-5-methyl-4-(piperidin-4-yl) aniline dihydrochloride monohydrate has a very good crystal form and is well suitable for recrystallization purification; further, the effect of impurity removal effect is very good, and any single impurity can be controlled less than 0.1%.
- -
-
Paragraph 0050-0054
(2018/04/20)
-
- 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.
- -
-
Paragraph 0253; 0254
(2018/03/25)
-
- Preparation color Switzerland for Nepal new intermediate and its preparation method
-
The invention relates to intermediates, namely a compound 1 of a formula (1) as shown in the specification and a compound 2 of a formula (2) as shown in the specification, for preparing ceritinib, or a chemically acceptable salt of the compound 2, wherein R represents the benzylic group of saturated or unsaturated aromatic ring methylene or heteroaromatic ring methylene, and X represents a halogen. The invention relates to a method for preparing a compound 4 by use of the new intermediates, namely the compound 1 and the compound 2, wherein the step of reduction from the compound 1 to the compound 2 is performed by use of a hydroboron or a composition thereof and an alcohol solvent; the compound 2 is reduced by use of a catalytic hydrogenation or transfer hydrogenation method to generate the compound 4. The route of preparing the compound 4 by use of the compound 1 and the compound 2 has the advantages that the chemical reduction step is combined with a catalytic hydrogenation, the use of expensive platinum dioxide is avoided and the cost of synthesizing the intermediate 4 of the ceritinib is effectively reduced.
- -
-
-
- 2-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 2-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.
- -
-
-
- Boryl-substituted aniline-based protein kinase inhibitor
-
The present invention discloses a compound capable of regulating protein kinase activity and used for treating or preventing protein kinase-related diseases, particularly relates to a boryl-substituted aniline-based protein kinase inhibitor, belongs to the compound capable of regulating the activity of anaplastic lymphoma kinase (ALK), and provides a preparation method of the compounds, and pharmaceutical uses of the compounds in treatment or prevention of ALK-related diseases.
- -
-
-
- Preparation method of 2-isopropoxy-5-methyl-4-(piperidine-4-yl) aniline dihydrochloride
-
The invention relates to a preparation method of 2-isopropoxy-5-methyl-4-(piperidine-4-yl) aniline dihydrochloride. The preparation method comprises the following steps: carrying out a nucleophilic substitution reaction, a coupling reaction and a reduction reaction by taking 1-chloro-5-fluoro-2-methyl-4-nitrobenzene as a starting material so as to obtain 1-benzyl-4-(5-isopropoxy-2-methyl-4-nitrophenyl)-1,2,3,6-tetrahydropyridine; carrying out a reduction reaction on the 1-benzyl-4-(5-isopropoxy-2-methyl-4-nitrophenyl)-1,2,3,6-tetrahydropyridine again to obtain the 2-isopropoxy-5-methyl-4-(piperidine-4-yl) aniline dihydrochloride. The method does not use catalysts such as platinum and rhodium, is simple and convenient in reaction technology and high in yield, avoids the high pressure reaction condition of the existing process, improves the safety, and shortens the reaction time, thus being suitable for mass production.
- -
-
-
- ALK KINASE INHIBITOR, AND PREPARATION METHOD AND USE THEREOF
-
An ALK kinase inhibitor compound as represented by Formula I, pharmaceutical composition containing the compound, and preparation method and use thereof in the preparation of drugs serving as an ALK inhibitor for treating cancer.
- -
-
Paragraph 0211; 0212; 0213
(2017/04/18)
-
- Ceritinib intermediate and preparation method and application thereof
-
The present invention discloses a ceritinib intermediate and a preparation method and application thereof. The ceritinib intermediate has a structure shown as a formula I, R and R2 are as defined in the specification and claims. The ceritinib intermediate is prepared from a compound of a formula 1 and a benzyl halide compound by substitution reaction and then reduction. After further reduction of the nitro by catalytic hydrogenation and removal of amino-protection, the compound of the formula I is reacted with a compound of a formula III to obtain ceritinib. According to the method, raw materials are readily available and inexpensive, the method does not require special equipment, production cost is greatly reduced, and the method is suitable for industrial application.
- -
-
Paragraph 0145-0148
(2017/02/28)
-
- Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro- N 2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)- N 4-(2-(isopropylsulfonyl) phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials
-
The synthesis, preclinical profile, and in vivo efficacy in rat xenograft models of the novel and selective anaplastic lymphoma kinase inhibitor 15b (LDK378) are described. In this initial report, preliminary structure-activity relationships (SARs) are described as well as the rational design strategy employed to overcome the development deficiencies of the first generation ALK inhibitor 4 (TAE684). Compound 15b is currently in phase 1 and phase 2 clinical trials with substantial antitumor activity being observed in ALK-positive cancer patients.
- Marsilje, Thomas H.,Pei, Wei,Chen, Bei,Lu, Wenshuo,Uno, Tetsuo,Jin, Yunho,Jiang, Tao,Kim, Sungjoon,Li, Nanxin,Warmuth, Markus,Sarkisova, Yelena,Sun, Frank,Steffy, Auzon,Pferdekamper, Annemarie C.,Li, Allen G.,Joseph, Sean B.,Kim, Young,Liu, Bo,Tuntland, Tove,Cui, Xiaoming,Gray, Nathanael S.,Steensma, Ruo,Wan, Yongqin,Jiang, Jiqing,Chopiuk, Greg,Li, Jie,Gordon, W. Perry,Richmond, Wendy,Johnson, Kevin,Chang, Jonathan,Groessl, Todd,He, You-Qun,Phimister, Andrew,Aycinena, Alex,Lee, Christian C.,Bursulaya, Badry,Karanewsky, Donald S.,Seidel, H. Martin,Harris, Jennifer L.,Michellys, Pierre-Yves
-
p. 5675 - 5690
(2013/08/23)
-
- COMPOUNDS AND COMPOSITIONS AS PROTEIN KINASE INHIBITORS
-
The invention provides novel pyrimidine and pyridine derivatives and pharmaceutical compositions thereof, and methods for using such compounds. For example, the pyrimidine and pyridine derivatives of the invention may be used to treat, ameliorate or prevent a condition which responds to inhibition of anaplastic lymphoma kinase (ALK) activity, focal adhesion kinase (FAK), zeta-chain-associated protein kinase 70 (ZAP-70), insulin-like growth factor (IGF-1R), or a combination thereof.
- -
-
Page/Page column 46
(2008/12/06)
-