132812-72-7

Basic information

• Product Name: 4-(4-Fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridin-2(1H)-one
• Synonyms: 4-(4-Fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridin-2(1H)-one;4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydro-1H-cyclooctapyridin-2-one;4-(4-Fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-2(1H)-one
• CAS NO: 132812-72-7
• Molecular Formula: C₁₇H₁₈FNO
• Molecular Weight: 271
• Product Categories: Aromatics;Heterocycles;Intermediates;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 132812-72-7.mol

Chemical Properties

• Boiling Point: 481.5±45.0 °C(Predicted)
• Appearance: /
• Density: 1.18
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 12.71±0.40(Predicted)
• CAS DataBase Reference: 4-(4-Fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridin-2(1H)-one(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(4-Fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridin-2(1H)-one(132812-72-7)
• EPA Substance Registry System: 4-(4-Fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridin-2(1H)-one(132812-72-7)

Safety Data

• Hazardous Substances Data: 132812-72-7(Hazardous Substances Data)

Usage

Uses

An intermediate of Blonanserin (B595850).

InChI:InChI=1S/C17H18FNO/c18-13-9-7-12(8-10-13)15-11-17(20)19-16-6-4-2-1-3-5-14(15)16/h7-11H,1-6H2,(H,19,20)

Upstream product

• 502-49-8 cycloactanone 
• 4640-67-9 3-(4-fluorophenyl)-3-oxopropionitrile 
• 403-33-8 methyl 4-flurobenzoate 
• 671188-82-2 3-(4-fluorophenyl)-3-oxopropanamide 
• 247179-37-9 1-(4-fluorophenyl)-2-methoxyethan-1-one 

Downstream Products

• 848301-82-6 2-(4-ethyl-piperazin-1-yl)-4-(4-fluoro-phenyl)-5,6,7,8,9,10-hexahydro-cycloocta[b]pyridin-8-ol 
• 143213-96-1 2-chloro-4-(4-fluoro-phenyl)-5,6,7,8,9,10-hexahydro-cycloocta[b]pyridine 1-oxide 
• 143213-95-0 2,10-dichloro-4-(4-fluoro-phenyl)-5,6,7,8,9,10-hexahydro-cycloocta[b]pyridine 
• 132813-14-0 2-chloro-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine 

Relevant articles and documents

An investigation into formation of impurities during synthesis of blonanserin

During the process development of Blonanserin (1 ), we have observed formations of unknown impurities are in the final product at enhanced levels which was identified as Des ethyl impurity, di-N-ethylpiperazine impurity, Chloro impurity and des-fluoro impurity. The present work involves detailed optimization studies directed toward the development of an efficient process for the commercial production of Blonanserin substantially free from the chloro impurity and other impurities.

Preparation method of blonanserin intermediate

The invention relates to a preparation method of a blonanserin intermediate, which comprises the following steps: hydrolyzing p-fluorobenzoyl acetonitrile in an aqueous solution in the presence of acid sulfate, then neutralizing with ammonia water until the pH value is 8-9, filtering and drying to obtain 3-(4-fluorophenyl)-3-oxopropanamide; and reacting 3-(4-fluorophenyl)-3-oxopropanamide with cyclooctanone in the presence of polyphosphoric acid and a catalyst, which is pyridine or a pyridine derivative, crystallizing in alkaline water, and pulping with methyl tert-butyl ether to obtain the blonanserin intermediate. The preparation method has the advantages of high product yield and few impurities, also has the advantage of high yield during large-scale production, and is suitable for industrial production.

High-efficiency preparation method of blonanserin intermediate

The invention discloses a high-efficiency preparation method of a blonanserin intermediate (BN-03). The method comprises the following two steps: (1) hydrolyzing p-fluorobenzoylacetonitrile by using 30% hydrogen peroxide in the presence of a composite catalyst composed of a heteropoly acid (a heteropoly acid salt) and a phase transfer catalyst under basic conditions in an organic solvent so as togenerate 3-(4-fluorophenyl)-3-oxo-propionamide; and (2) performing a reaction on 3-(4-fluorophenyl)-3-oxo-propionamide and cyclooctanone under the catalysis of an acid in at least one organic solventso as to obtain 4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-2(1H)-one. The total yield of the product is increased from 63.5% to about 85%.

METHOD OF PRODUCING BLONANSERIN

PROBLEM TO BE SOLVED: To provide a method of producing blonanserin. SOLUTION: The invention relates to an improved method of producing high-purity 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine (INN name blonanserin). The method is implemented through four successive steps starting from C1-4-alkyl 4-fluorobenzoate. The invention also relates to a method of producing 3-(4-fluorophenyl)-3-oxopropanenitrile (BLON1) being an intermediate. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT

Synthetic method for Blonanserin

The invention discloses a synthetic method for Blonanserin. The synthetic method comprises the following steps: 1) methyl fluorobenzoate is taken as a raw material and subjected to condensation with acetonitrile, and a compound 3 is obtained; 2) polyphosphoric acid is heated, then the compound 3 and a cyclooctanone and an ionic liquid are added, and a compound 4 is obtained through a one-step reaction; 3) the compound 4 is subjected to chlorination through a phenylphosphonic dichloride compound, and a compound 5 is obtained; 4) the compound 5 is mixed with potassium iodide and 1-ethylpiperazine, the ionic liquid is added, heating and nucleophilic substitution are performed, and Blonanserin is obtained, wherein the ionic liquid in the step 2) and the step 3) is 1-ethyl-3-methylimidazolium tetrafluoroborate, the adding quantity of the ionic liquid in the step 2) is 30% of the mass of the compound 3, and the adding quantity of the ionic liquid in the step 3) is 30% of the mass of the compound 5. Compared with the conventional synthetic method for Blonanserin, the synthetic method has the advantages that the reaction time is shortened greatly, the yield is increased, the production cost is reduced, and the method is applicable to industrial production.

NEW PROCESS FOR THE PREPARATION OF BLONANSERIN INTERMEDIATE

The present invention relates to a novel method for manufacturing 4-(4-flourophenyl)-5,6,7,8,9,10-hexahydrocyclocta[b]pyridi-2(1H)-on, which is an intermediate body of blonanserin used as an agent for treating schizophrenia. According to the manufacturing method of the present invention, the 4-(4-flourophenyl)-5,6,7,8,9,10-hexahydrocyclocta[b]pyridi-2(1H)-on can be manufactured in an economic and efficient manner.COPYRIGHT KIPO 2016

Syntheses and properties of the major hydroxy metabolites in humans of blonanserin AD-5423, a novel antipsychotic agent

Two major metabolites in humans of blonanserin, 2-(4-ethyl-1-piperazinyl)- 4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta-[b]pyridine (code name AD-5423), were synthesized. The first, 7-hydroxylated AD-5423, was synthesized through a four-step process