877399-00-3

Usage

Uses

Used in Pharmaceutical Industry:
(R)-5-bromo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine is used as a key intermediate in the synthesis of Crizotinib, an antineoplastic drug. Crizotinib is a tyrosine kinase inhibitor that targets anaplastic lymphoma kinase (ALK) and has been approved for the treatment of non-small cell lung cancer (NSCLC) patients with ALK rearrangements. (R)-5-bromo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine's unique structure allows it to interact with the kinase domain of ALK, thereby inhibiting its activity and reducing tumor growth.
As a chiral intermediate, (R)-5-bromo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine is essential for the production of enantiomerically pure Crizotinib, ensuring the desired therapeutic effects and minimizing potential side effects associated with the less active or unwanted enantiomer.

Upstream product

• 877397-65-4 (S)‐1‐(2,6-dichloro-3-fluorophenyl)ethanol 
• 15128-82-2 3-hydroxy-2-nitropyridine 
• 877397-70-1 (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethyoxyl)-2-nitropyridine 
• 877397-71-2 (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethyoxyl)-2-aminopyridine 
• 74115-13-2 5-bromopyridine-3-ol 
• 1394346-24-7 (R)-5-bromo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-nitropyridine 
• 35486-42-1 2-amino-3,5-dibromopyridine 
• 330156-50-8 (R)-1-(2,6-dichloro-3-fluorophenyl)ethan-1-ol 
• 54231-35-5 3-fuoro-2-nitropyridine 
• 877399-98-9 C₉H₉Cl₂FO₃S 
• 756520-66-8 1-(2,6-dichloro-3-fluorophenyl)ethanol 
• 756521-08-1 (±)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-nitropyridine 
• 290835-85-7 2',6'-dichloro-3'-fluoroacetophenone 
• 877397-71-2 (S)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-aminopyridine 

Downstream Products

• 877399-52-5 crizotinib 

Relevant academic research and scientific papers

Preparation method of deuterated crizotinib and derivatives thereof

The invention relates to a preparation method of deuterated crizotinib and derivatives thereof, and belongs to the technical field of synthesis of medical compounds. Four deuterated crizotinib with different configurations are synthesized, the influence of the deuterated position and different chirality of the deuterated crizotinib on the biological activity and the drug metabolism property of thecrizotinib is investigated, and the result shows that the deuterated crizotinib and the crizotinib have similar anti-cancer activity. Compared with a deuterated crizotinib raceme and crizotinib, thedeuterated crizotinib has certain physicochemical property advantages, has good anticancer application prospects, and provides a new compound for synthesis of novel antitumor drugs. The resolution ofthe racemate phenylethanol derivative is a key step for synthesizing the deuterated crizotinib, the ee value of the racemate phenylethanol derivative directly influences the ee value of a final product, and the resolution method has the characteristics of easiness in operation, low cost and the like.

Novel pyridine derivatives having inhibition activity against SHIP2 and pharmaceutical compositions with the components

The present invention relates to a use as a pyridine derivative and/or a SHIP2 inhibitor. More specifically, the present invention relates to: a pyridine derivative of chemical formula I or pharmaceutically acceptable salt thereof; a method for manufacturing compounds thereof; and a pharmaceutical composition containing the compounds as active components. The pyridine derivative and the pharmaceutically acceptable salt thereof are useful as therapeutic agents for diseases related to SHIP2, such as Alzheimerandprime;s dementia, hypertension, cancer, diabetes, etc.COPYRIGHT KIPO 2020

Novel pyridine derivatives having inhibition activity against SHIP2 and pharmaceutical compositions with the components

The present invention relates to a pyridine derivative and/or a use as a SHIP2 inhibitor. The present invention relates to a pyridine derivative of chemical formula I or a pharmaceutically acceptable salt thereof, a method for preparing the compounds, and a pharmaceutical composition containing the compounds as an active ingredient. The pyridine derivative and pharmaceutically acceptable salt thereof is useful as drugs for the treatment of diseases related to SHIP2, such as Alzheimerandprime;s dementia, hypertension, cancer, and diabetes.COPYRIGHT KIPO 2021

Novel synthesis method of crizotinib intermediate (by machine translation)

The invention relates to a synthesis method of an organic compound, in particular to a novel synthesis method of a crizotinib intermediate, which comprises the following steps: taking cheap and easily available 2,6 - dichloro -3 - fluoroacetophenone as a starting raw material and reducing the CBS system to obtain S-shaped chiral alcohol. , 2 - Aminopyridine is taken as a raw material and bromine is brominated to obtain 3,5 - dibromo -2 - aminopyridine. The compound is condensed into an ether with a chiral alcohol under the action of an acid-binding agent to obtain the intermediate of the required configuration. The method is simple in reaction, short in route, less in three wastes, environment-friendly, high in yield of all steps, and less in raw material and reagent waste. (by machine translation)

Synthesis of a Crizotinib Intermediate via Highly Efficient Catalytic Hydrogenation in Continuous Flow

Kilogram-scale highly selective catalytic hydrogenation of the aryl nitro group in the intermediate of crizotinib has been developed, which adopted continuous-flow technology with prepassivated Raney Ni as a catalyst at room temperature. According to the reaction condition optimization, side reactions such as dehalogenation, debenzylation, and reduction of other unsaturated functional groups were inhibited eminently. Moreover, catalytic hydrogenation of (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-nitropyridine (compound I) afforded the desired product (R)-3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-2-amine (compound II) with high selectivity (99.9%) and high conversion (99.5%). Finally, high-quality crizotinib was synthesized from intermediate II.

Discovery of 2-aminopyridines bearing a pyridone moiety as potent ALK inhibitors to overcome the crizotinib-resistant mutants

Despite the initial benefit demonstrated in clinical setting with ALK inhibitors, the challenging resistant mutants (F1174L, L1196M and G1202R) invariably developed. In this work, a series of 2-aminopyridine derivatives were designed and synthesized by C-5 position incorporation of a 2-pyridone moiety and bioisosteric replacement of the C-3 position linkers. Optimization of the 2-aminopyridine derivatives led to the identification of hit 18d displaying a significant growth inhibition against a variety of ALK-addicted cancer cells. Especially in the case of ALK-positive Karpas-299 cell, 18d exhibited excellent anti-proliferative potency with an IC50 value of about 40 nM. Moreover, 18d demonstrated encouraging activities against wild-type ALK (19 nM), ROS1 (2.3 nM) as well as challenging crizotinib-resistant ALKL1196M and ALKG1202R mutants with IC50 values of 45 nM and 22 nM, respectively. Additionally flow cytometric analysis indicates that 18d inhibited Karpas-299 cell viability via G1 phase arrest. Taken together, this work provided a promising ALK inhibitor to circumvent the clinical crizotinib-resistant mutants.

Design, synthesis and structure-activity relationship study of aminopyridine derivatives as novel inhibitors of Janus kinase 2

Janus Kinase 2 (JAK2) is a kind of intracellular non-receptor protein tyrosine kinase and has been certified as an important target for the treatment of myeloproliferative neoplasms and rheumatoid arthritis. However, the low selectivity and potential safety issues restrict the clinical applications of JAK2 inhibitors. Here we found that crizotinib showed good inhibitory activity against JAK2 by enzymatic assays (IC50 = 27 nM). Then we carried out structure-based drug design and synthesized a series of compounds with an aminopyridine scaffold. Finally, compound 12k and 12l were identified as the promising inhibitors of JAK2, which exhibited high inhibitory activity (IC50 = 6 nM and 3 nM, respectively) and selectivity for JAK2 over JAK1 and JAK3, and showed potent antiproliferative activities toward HEL human erythroleukemia cells. Moreover, 12k suppressed symptoms of the collagen-induced arthritis (CIA) model in rats.

A method for synthesizing intermediate [...]

The invention discloses a method for synthesizing intermediate [...], belongs to the technical field of intermediate synthesis, is 2 - amino - 3 - hydroxy - 5 - bromo pyridine and (S)- 1 - (2, 6 - dichloro - 3 - fluoro phenyl) ethanol as the raw material,

PYRIDINE SUBSTITUTED 2-AMINOPYRIDINE PROTEIN KINASE INHIBITOR CRYSTAL

The present invention discloses a crystal of citrate salt of pyridine-substituted 2-aminopyridine-based protein kinase inhibitors, in particular, to crystal of 5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-4′-methoxy-6′-((S)-2-methylpiperazin-1-yl)-3,3′-bipyridin-6-amine citrate salt, a method for preparation thereof, a crystalline composition and a pharmaceutical composition comprising the crystal, and further discloses the use of crystals of citrate salt of the compound of Formula I in protein kinase-related diseases. The crystals of citrate salt according to the present invention are superior to 5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-4′-methoxy-6′-((S)-2-methylpiperazin-1-yl)-3,3′-bipyridin-6-amine or other salts of 5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-4′-methoxy-6′-((S)-2-methylpiperazin-1-yl)-3,3′-bipyridin-6-amine in at least one aspect of bioavailability, hygroscopicity, stability, solubility, purity, ease of preparation, and the like.

Crizotinib intermediate, preparation method and crizotinib preparation method

The invention relates to a crizotinib intermediate, a preparation method and a crizotinib preparation method, in particular to an intermediate of crizotinib which has the structure of a formula (CZT-5) as shown in the description and the structure of a formula (CZT-9) as shown in the description, a preparation method of the intermediate and a preparation method of a crizotinib with the structure of a formula (CZT-11). The method provided by the invention has the characteristics of short route, high yield, easiness in acquisition of raw materials, high reaction selectivity and the like, chiral resolution is not required in a synthetic process, the utilization rate of the raw materials is increased, the path costs are low, and therefore, the method can meet requirements of large-scale industrial production.