molecular formula C20H21ClN2 B194729 8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine CAS No. 38092-89-6

8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine

Cat. No.: B194729
CAS No.: 38092-89-6
M. Wt: 324.8 g/mol
InChI Key: VLXSCTINYKDTKR-UHFFFAOYSA-N
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Mechanism of Action

Desloratadine, a related compound, competes with free histamine for binding at H1-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms .

Safety and Hazards

N-Methyldesloratadine should be handled with care. Avoid dust formation, breathing mist, gas or vapours, and contact with skin and eye. Use personal protective equipment and ensure adequate ventilation .

Preparation Methods

The preparation of 8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine involves several synthetic routes. One common method includes dissolving Loratadine in an alcohol solvent under nitrogen protection, followed by the addition of potassium hydroxide. The mixture is then heated to 70-75°C and refluxed until the reaction is complete. The reaction solution is then extracted with ethyl acetate, and the product is crystallized and purified . Industrial production methods may involve similar steps but on a larger scale with optimized reaction conditions to ensure high yield and purity.

Chemical Reactions Analysis

8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine undergoes various chemical reactions, including:

    Oxidation: This reaction can be carried out using oxidizing agents such as potassium permanganate or hydrogen peroxide.

    Reduction: Common reducing agents like lithium aluminum hydride can be used to reduce this compound.

    Substitution: Halogenation reactions can introduce halogen atoms into the compound, while nucleophilic substitution reactions can replace existing functional groups with nucleophiles.

The major products formed from these reactions depend on the specific reagents and conditions used. For example, oxidation may yield hydroxylated derivatives, while reduction can produce dechlorinated products .

Properties

IUPAC Name

13-chloro-2-(1-methylpiperidin-4-ylidene)-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene
Source PubChem
URL https://pubchem.ncbi.nlm.nih.gov
Description Data deposited in or computed by PubChem

InChI

InChI=1S/C20H21ClN2/c1-23-11-8-14(9-12-23)19-18-7-6-17(21)13-16(18)5-4-15-3-2-10-22-20(15)19/h2-3,6-7,10,13H,4-5,8-9,11-12H2,1H3
Source PubChem
URL https://pubchem.ncbi.nlm.nih.gov
Description Data deposited in or computed by PubChem

InChI Key

VLXSCTINYKDTKR-UHFFFAOYSA-N
Source PubChem
URL https://pubchem.ncbi.nlm.nih.gov
Description Data deposited in or computed by PubChem

Canonical SMILES

CN1CCC(=C2C3=C(CCC4=C2N=CC=C4)C=C(C=C3)Cl)CC1
Source PubChem
URL https://pubchem.ncbi.nlm.nih.gov
Description Data deposited in or computed by PubChem

Molecular Formula

C20H21ClN2
Source PubChem
URL https://pubchem.ncbi.nlm.nih.gov
Description Data deposited in or computed by PubChem

DSSTOX Substance ID

DTXSID40191502
Record name N-Methyldesloratadine
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Molecular Weight

324.8 g/mol
Source PubChem
URL https://pubchem.ncbi.nlm.nih.gov
Description Data deposited in or computed by PubChem

CAS No.

38092-89-6
Record name N-Methyldesloratadine
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Record name N-Methyldesloratadine
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Record name N-Methyldesloratadine
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Record name 8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
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Record name N-METHYLDESLORATADINE
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Synthesis routes and methods I

Procedure details

A solution of 177 g (0.49 mole) of a product of Step D above in 480 mL (814.1 g, 5.31 mole) of trifluoromethanesulfonic acid at 90°-95° C. for 18 hours under nitrogen. Completeness of the reaction is determined by thin-layer chromatography. The cooled reaction is quenched with ice-water and the pH is adjusted to 6 with barium carbonate. The product is extracted into methylene chloride, which is concentrated under reduced pressure to about 1 liter and washed with water. The product is extracted into 1N hydrochloric acid, which is treated with 30 g of Darco, and filtered through celite. The pH of the filtrate is adjusted to 10 with 50% aqueous sodium hydroxide and the product is extracted into methylene chloride, which is removed under reduced pressure. The residue is dissolved in hot hexane, which is filtered to remove insolubles. The filtrate is concentrated to a residual beige powder. Yield: 126 g (HPLC purity 80%), 65% of theory.
Quantity
177 g
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480 mL
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Synthesis routes and methods II

Procedure details

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Synthesis routes and methods III

Procedure details

To a solution of [3-[2-(3-chlorophenyl)ethyl]-2-pyridinyl]-1-methyl-4-piperidinyl methanone hydrochloride (59.0 g; 0.15 mol) in 120 mL (120 g; 6.0 mol) of hydrofluoric acid at -35° C. was added boron trifluoride (44.3 g; 0.66 mol) over 1 h. The reaction was quenched using ice water and potassium hydroxide to a final pH of 10. The product was extracted into toluene which was washed with water and brine. The toluene solution was concentrated to a residue which was triturated with hot hexanes. Insoluble salts were removed by filtration and the filtrate was concentrated to give as a main product 45.7 g (HPLC purity 96%, yield 91%) of 8-chloro-6,11-dihydro- 11-(1-methyl-4-piperidinylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine as an off-white solid: mp 116°-119° C.; NMR (200 MHz, CDCl3)δ2.0-2.2 (m,2H), 2.27 (s,3H), 2.3-2.6 (m,4H), 2.6-3.0 (m,4H), 3.3-3.6 (m,2H), 7.0-7.2 (m,4H), 7.44 (dd,1H,J=8, 2 Hz), 8.42 (dd,1H,J=3, 2 Hz); mass spectrum, m/e (rel intensity) 327M+3 (28), 325M+1 (100) Anal. Calcd. for C20H21N2Cl: C,73.94; H,6.52; N,8.63; Cl,10.92. Found: C,73.88; H,6.48; N,8.69; Cl10.80. This material was found to include the two corresponding fluoro-substituted compound of the invention as discussed further below.
Quantity
120 mL
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44.3 g
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Retrosynthesis Analysis

AI-Powered Synthesis Planning: Our tool employs the Template_relevance Pistachio, Template_relevance Bkms_metabolic, Template_relevance Pistachio_ringbreaker, Template_relevance Reaxys, Template_relevance Reaxys_biocatalysis model, leveraging a vast database of chemical reactions to predict feasible synthetic routes.

One-Step Synthesis Focus: Specifically designed for one-step synthesis, it provides concise and direct routes for your target compounds, streamlining the synthesis process.

Accurate Predictions: Utilizing the extensive PISTACHIO, BKMS_METABOLIC, PISTACHIO_RINGBREAKER, REAXYS, REAXYS_BIOCATALYSIS database, our tool offers high-accuracy predictions, reflecting the latest in chemical research and data.

Strategy Settings

Precursor scoring Relevance Heuristic
Min. plausibility 0.01
Model Template_relevance
Template Set Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis
Top-N result to add to graph 6

Feasible Synthetic Routes

Reactant of Route 1
8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
Reactant of Route 2
Reactant of Route 2
8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
Reactant of Route 3
Reactant of Route 3
8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
Reactant of Route 4
Reactant of Route 4
8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
Reactant of Route 5
Reactant of Route 5
8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
Reactant of Route 6
Reactant of Route 6
8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
Customer
Q & A

Q1: What analytical techniques are commonly employed to quantify loratadine and its related compounds, including N-Methyldesloratadine, in biological samples?

A1: High-performance liquid chromatography (HPLC) coupled with various detection methods is widely used for quantifying loratadine and its metabolites, including N-Methyldesloratadine. For instance, one study employed a validated ion pair liquid chromatography method with fluorescence detection (IPLC/FLD) to determine loratadine and its primary metabolite, descarboethoxyloratadine, in human plasma. [] This method utilized a simple liquid-liquid extraction for sample preparation and achieved high sensitivity, enabling the determination of low analyte concentrations. Another study utilized HPLC with diode array detection and mass spectrometry (HPLC/DAD/MS) for a comprehensive analysis of loratadine and its impurities, including N-Methyldesloratadine. [] This approach combined the separation power of HPLC with the identification capabilities of mass spectrometry, enabling the structural elucidation of an unknown impurity.

Q2: Can you elaborate on the applications of HPLC in assessing the quality of loratadine drug products?

A2: HPLC plays a crucial role in controlling the quality of loratadine drug products by enabling the quantification of the active ingredient and the detection of impurities. [] Researchers developed an HPLC method using an Agilent TC-C18 column and a gradient elution with acetonitrile and 2% acetic acid to determine the content of loratadine and related substances. [] This method demonstrated good separation efficiency for loratadine and impurities like N-Methyldesloratadine, desloratadine, and others, making it suitable for quality control and research purposes.

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