330156-50-8

Usage

Uses

Used in Pharmaceutical Industry:
(R)-1-(2,6-Dichloro-3-fluorophenyl)ethanol is used as a pharmaceutical intermediate for the synthesis of Crizotinib (C785000), an anti-tumor molecular targeted drug. This intermediate plays a vital role in the development of drugs that specifically target tumor cells, offering a more precise and effective treatment approach for cancer patients.
In the synthesis of Crizotinib, (R)-1-(2,6-Dichloro-3-fluorophenyl)ethanol contributes to the formation of the drug's active pharmaceutical ingredient (API), which is designed to inhibit specific molecular targets within tumor cells. This targeted approach helps minimize side effects and improve the overall efficacy of the treatment.

InChI:InChI=1/C8H7Cl2FO/c1-4(12)7-5(9)2-3-6(11)8(7)10/h2-4,12H,1H3/t4-/m1/s1

Upstream product

• 290835-85-7 2',6'-dichloro-3'-fluoroacetophenone 
• 756520-66-8 1-(2,6-dichloro-3-fluorophenyl)ethanol 
• 877397-67-6 1-(2,6-dichloro-3-fluorophenyl)ethyl acetate 

Downstream Products

• 877397-70-1 (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethyoxyl)-2-nitropyridine 
• 1370651-29-8 C₁₂H₉Cl₃FN₃O 
• 1201916-93-9 C₃₀H₃₄Cl₂FN₅O₇ 
• 1201916-63-3 {6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]-pyridazin-3-yl}-N-(1-ethyl-6-oxo-1,6-dihydro-pyridin-3-yl)carboxamide 
• 1370651-32-3 C₂₂H₂₅Cl₃FN₃O₅ 
• 1370651-34-5 C₂₅H₃₀Cl₂FN₃O₇ 
• 1370651-36-7 6-[bis(tert-butoxycarbonyl)amino]-5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazine-3-carboxylic acid 
• 1370652-58-6 C₂₉H₃₂Cl₂FN₅O₇ 
• 1370652-56-4 {5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-6-aminopyridazin-3-yl}-N-(1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)carboxamide 
• 1365267-27-1 6-amino-5-[(1{R})-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-{N}-[4-[(3{R},5{S})-3,5-dimethylpiperazine-1-carbonyl]phenyl]pyridazine-3-carboxamide 
• 1370651-39-0 C₃₅H₄₁Cl₂FN₆O₇ 
• 1370651-40-3 C₃₅H₃₄Cl₂FN₅O₇ 
• 1370651-02-7 {5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-6-aminopyridazin-3-yl}-N-[4-(4-pyridylcarbonyl)phenyl]carboxamide 
• 1407496-16-5 C₂₄H₂₀Cl₂F₄N₆O 

Relevant academic research and scientific papers

Biotransformation-mediated synthesis of (1S)-1-(2,6-dichloro-3- fluorophenyl)ethanol in enantiomerically pure form

An efficient four-step biotransformation-mediated synthesis of (1S)-1-(2,6-dichloro-3-fluorophenyl)ethanol in enantiomerically pure form is described. This compound is a key intermediate required for the preparation of PF-2341066, a potent inhibitor of c-

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)

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.

Manganese-Catalyzed Enantioselective Hydrogenation of Simple Ketones Using an Imidazole-Based Chiral PNN Tridentate Ligand

A series of Mn(I) catalysts containing imidazole-based chiral PNN tridentate ligands with controllable 'side arm' groups have been established, enabling the inexpensive base-promoted asymmetric hydrogenation of simple ketones with outstanding activities (up to 8200 TON) and good enantioselectivities (up to 88.5percent ee). This protocol features wide substrate scope and functional group tolerance, thereby providing easy access to a key intermediate of crizotinib.

Chiral ferrocene phosphine-nitrogen-nitrogen tridentate ligand as well as preparation method and application thereof

The invention discloses a chiral ferrocene phosphine-nitrogen-nitrogen tridentate ligand as well as a preparation method and an application thereof. The general structural formula of the chiral ferrocene phosphine-nitrogen-nitrogen tridentate ligand is shown in formula (I) or formula (II), wherein R1 and R2 are independently selected from C1-C6 alkyl, C3-C6 cycloalkyl, aryl or heterocyclic aryl respectively; R3 is aryl, heterocyclic aryl or C1-C6 alkyl, and R4 is hydrogen, C1-C6 alkyl, aryl or heterocyclic aryl; the general structural formula in the formula (I) and the formula (II) contains animidazole group or a substituted benzimidazole group respectively; one or more substituent groups exist on a benzene ring of the substituted benzimidazole group, and each substituent group is independently selected from H or C1-C4 alkyl. The chiral ferrocene phosphine-nitrogen-nitrogen tridentate ligand has the advantages that the tridentate ligand is convenient to synthesize, exists in the air stably and can be coordinated with cheap metal to prepare a cheap metal catalyst, and the cheap metal catalyst is well applied to asymmetric hydrogenation reactions of ketone.

Towards practical earth abundant reduction catalysis: Design of improved catalysts for manganese catalysed hydrogenation

Manganese catalysts derived from tridentate P,N,N ligands can be activated easily using weak bases for both ketone and ester hydrogenations. Kinetic studies indicate the ketone hydrogenations are 0th order in acetophenone, positive order in hydrogen and 1st order in the catalyst. This implies that the rate determining step of the reaction was the activation of hydrogen. New ligand systems with varying donor strength were studied and it was possible to make the hydrogen activation significantly more efficient; a catalyst displaying around a 3-fold increase in initial turn-over frequencies for the hydrogenation of acetophenone relative to the parent system was discovered as a result of these kinetic investigations. Ester hydrogenations and ketone transfer hydrogenation (isopropanol as reductant) are first order for both the substrate and catalysts. Kinetic studies also gained insight into catalyst stability and identified a working range in which the catalyst is stable throughout the catalytic reaction (and a larger working range where high yields can still be achieved). The new more active catalyst, combining an electron-rich phosphine with an electron-rich pyridine is capable of hydrogenating acetophenone using as little as 0.01 mol% catalyst at 65 °C. In all, protocols for reduction of 21 ketones and 15 esters are described.

Synthesis process of crizotinib intermediate

The invention discloses a synthesis process of a crizotinib intermediate. The synthesis process comprises the following steps: with 2,6-dichloro-3-fluoroacetophenone as the raw material in an alkali and solvent environment and hydrogen as a reducing agent

Synthesis method of crizotinib and preparation method of crizotinib intermediate compound

The invention provides a synthesis method of crizotinib and a preparation method of a crizotinib intermediate compound. The synthesis method of the crizotinib comprises the following steps: reacting N-protected 4-(3-(5-fluoro-6-nitropyridine-3-yl)-1H-pyrazole-1-yl)piperidine (9) used as a raw material and a chiral intermediate compound (3) to obtain a key chiral intermediate compound; and performing reduction on the chiral intermediate compound, and performing deprotection to obtain the target compound crizotinib (1). According to the invention, the advantages of accessible raw materials, mild reaction conditions and simple operation process are achieved; and a catalyst has favorable stability and activity, and is easy to recover and use indiscriminately, thereby facilitating the large-scale preparation and production of the crizotinib.

A Highly Active Manganese Catalyst for Enantioselective Ketone and Ester Hydrogenation

A new hydrogenation catalyst based on a manganese complex of a chiral P,N,N ligand has been found to be especially active for the hydrogenation of esters down to 0.1 mol % catalyst loading, and gives up to 97 % ee in the hydrogenation of pro-chiral deactivated ketones at 30–50 °C.

CRIZOTINIB FOR USE IN THE TREATMENT OF CANCER

The present invention relates to the use of ROS kinase inhibitors for treating abnormal cell growth in mammals. In particular, the invention provides methods of treating mammals suffering from cancer mediated by at least one genetically altered ROS. In particular, the invention provides methods of treating mammals suffering from cancer mediated by at least one genetically altered ROS by administration of crizotinib.