38089-93-9

Basic information

• Product Name: 8-Chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol
• Synonyms: 8-CHLORO-6,11-DIHYDRO-11-(1-METHYL-4-PIPERIDINYL)-5H-BENZO[5,6]CYCLOHEPTA[1,2-B]PYRIDIN-11-OL;8-Chloro-6,11-Dihydro-11-(4-Piperidinyl methyl)-5H-Benzo[5,6]Cyclohepta-[1,2-b]P;8-Chloro-6,11-dihydro-11-(4-piperidinylmethyl)-5H-benzo[5.6]cyclohepta[1.2-b]pyridinemethanol;8-chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-B]pyridin-11-ol (intermediate of loratadine);8-CHLORO-6,11-DIHYDRO-11-(1-METHYL-4-PIPERIDINYL)-5H-BENZO[5,6] CYCLOHEPTA[1,2-B]PYRIDIN-11-OL, 99+%;11-Hydroxy-N-Methyl Dihydro Loratadine;Loratadine USP Related CoMpound D;5H-Benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol, 8-chloro-6,11-dihydro-11-(1-Methyl-4-piperidinyl)-
• CAS NO: 38089-93-9
• Molecular Formula: C₂₀H₂₃ClN₂O
• Molecular Weight: 342.86
• Product Categories: (intermediate of loratadine)
• Mol File: 38089-93-9.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 478.12 °C at 760 mmHg
• Flash Point: 242.958 °C
• Appearance: /
• Density: 1.244 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.621
• Storage Temp.: Inert atmosphere,Store in freezer, under -20°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 12.25±0.20(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: 8-Chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol(CAS DataBase Reference)
• NIST Chemistry Reference: 8-Chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol(38089-93-9)
• EPA Substance Registry System: 8-Chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol(38089-93-9)

Safety Data

• Hazardous Substances Data: 38089-93-9(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 38089-93-9 differently. You can refer to the following data:
1. 11-Hydroxy-N-methyl Dihydroloratadine is an impurity of Loratadine (L469575).
2. 11-Hydroxy-N-methyl Dihydroloratadine (Loratadine USP Related Compound D) is an impurity of Loratadine (L469575).

InChI:InChI=1/C20H23ClN2O/c1-23-11-8-16(9-12-23)20(24)18-7-6-17(21)13-15(18)5-4-14-3-2-10-22-19(14)20/h2-3,6-7,10,13,16,24H,4-5,8-9,11-12H2,1H3

Synthetic route

8-chloro-5,6-dihydro-11H-Benzo[5,6]cyclohepta[1,2-b]pyridin-11-one (31251-41-9) + (1-methyl-4-piperidyl)magnesium chloride (63463-36-5) → 8-chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol (38089-93-9)

Conditions	Yield
In tetrahydrofuran Reflux;	95%
With (trimethylsilyl)methylmagnesium chloride; lithium chloride; zinc(II) chloride In tetrahydrofuran; diethyl ether at 0℃; for 2h; Inert atmosphere;	90%
In tetrahydrofuran at -95 - -15℃; for 2 - 3h;	71.1%

4-chloro-1-methylpiperidine (5570-77-4) + 8-chloro-5,6-dihydro-11H-Benzo[5,6]cyclohepta[1,2-b]pyridin-11-one (31251-41-9) → 8-chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol (38089-93-9)

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With magnesium; ethylene dibromide In tetrahydrofuran at 20 - 48℃; Stage #2: 8-chloro-5,6-dihydro-11H-Benzo[5,6]cyclohepta[1,2-b]pyridin-11-one In tetrahydrofuran at -80 - -70℃; for 2 - 3h; Product distribution / selectivity;	73.6%

8-chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol (38089-93-9) → N-methyldesloratadine (38092-89-6)

Conditions	Yield
With sulfuric acid at 20℃; for 4.5h;	85%
With sulfuric acid at 35 - 45℃; for 2 - 3h;	80%
Stage #1: 8-chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol With sulfuric acid at 35 - 45℃; for 2 - 3h; Stage #2: In water pH=8 - 9; Product distribution / selectivity;

8-chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol (38089-93-9) → 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-N-(2-methoxyphenyl)-1-piperidinecarbothioamide (1373612-35-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: sulfuric acid / 4.5 h / 20 °C 2: triethylamine / toluene / 3 h / Reflux 3: potassium hydroxide / ethanol / 6 h / Reflux 4: ethanol / 1 h / 20 °C View Scheme

8-chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol (38089-93-9) → 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-N-methyl-1-piperidinecarbothioamide (929968-46-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: sulfuric acid / 4.5 h / 20 °C 2: triethylamine / toluene / 3 h / Reflux 3: potassium hydroxide / ethanol / 6 h / Reflux 4: ethanol / 1 h / 20 °C View Scheme

8-chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol (38089-93-9) → 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-N-cyclohexyl-1-piperidinecarbothioamide (1373612-32-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: sulfuric acid / 4.5 h / 20 °C 2: triethylamine / toluene / 3 h / Reflux 3: potassium hydroxide / ethanol / 6 h / Reflux 4: ethanol / 1 h / 20 °C View Scheme

8-chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol (38089-93-9) → 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-N-phenyl-1-piperidinecarbothioamide (1373612-33-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: sulfuric acid / 4.5 h / 20 °C 2: triethylamine / toluene / 3 h / Reflux 3: potassium hydroxide / ethanol / 6 h / Reflux 4: ethanol / 1 h / 20 °C View Scheme

8-chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol (38089-93-9) → 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-N-(2-methylphenyl)-1-piperidinecarbothioamide (1373612-34-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: sulfuric acid / 4.5 h / 20 °C 2: triethylamine / toluene / 3 h / Reflux 3: potassium hydroxide / ethanol / 6 h / Reflux 4: ethanol / 1 h / 20 °C View Scheme

8-chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol (38089-93-9) → descarboethoxyloratadine (100643-71-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: sulfuric acid / 4.5 h / 20 °C 2: triethylamine / toluene / 3 h / Reflux 3: potassium hydroxide / ethanol / 6 h / Reflux View Scheme

8-chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol (38089-93-9) → loratadine (79794-75-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: sulfuric acid / 4.5 h / 20 °C 2: triethylamine / toluene / 3 h / Reflux View Scheme

Upstream product

• 5570-77-4 4-chloro-1-methylpiperidine 
• 31251-41-9 8-chloro-5,6-dihydro-11H-Benzo[5,6]cyclohepta[1,2-b]pyridin-11-one 
• 63463-36-5 (1-methyl-4-piperidyl)magnesium chloride 

Downstream Products

• 79794-75-5 loratadine 
• 100643-71-8 descarboethoxyloratadine 
• 1373612-34-0 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-N-(2-methylphenyl)-1-piperidinecarbothioamide 
• 1373612-33-9 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-N-phenyl-1-piperidinecarbothioamide 
• 1373612-32-8 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-N-cyclohexyl-1-piperidinecarbothioamide 
• 1373612-35-1 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-N-(2-methoxyphenyl)-1-piperidinecarbothioamide 
• 38092-89-6 N-methyldesloratadine 

Relevant articles and documents

Benzocycloheptanopyridine compound, and preparation method and application thereof

The invention belongs to the field of medicines, and particularly relates to a benzocycloheptanopyridine compound, and a preparation method and application thereof, wherein the benzocycloheptanopyridine compound has a structure represented by a formula IV described in the specification. The preparation method comprises the steps: heating magnesium and N-methyl-4-chloropiperidine in a first reaction solvent under the action of an initiator for reaction to obtain a Grignard reagent; carrying out a reaction on 8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepto[1,2-b]pyridine-11-one and a Grignard reagent in a second reaction solvent to obtain a compound I; and carrying out a reaction on the compound I in a third reaction solvent under the action of a reducing agent to obtain a compound IV. The benzocycloheptanopyridine compound prepared by the preparation method is high in purity, can detect and monitor the compound IV in the loratadine synthesis process, and is of great significance in improving the quality of loratadine bulk drugs or preparations thereof.

Design and synthesis of thiourea derivatives containing a benzo[5,6]cyclohepta[1,2-b]pyridine moiety as potential antitumor and anti-inflammatory agents

Thiourea derivatives (6a-e) were developed and screened for antitumor and anti-inflammatory activity. Most of the compounds exhibited growth inhibitory effects comparable to 5-fluorouracil in vitro against mammary (MCF-7 and MDA-MB 231) as well as colon (HT-29) carcinoma cells. They also showed stronger anti-inflammatory activity than ibuprofen in vivo in the xylene-induced ear swelling assay in mice.

A PROCESS FOR THE MANUFACTURING OF LORATADINE AND ITS INTERMEDIATES

The process comprises (i) subjecting substituted benzyl halide to cyanation in a biphasic system using water immiscible solvents by any known methods, (ii) condensing in situ the phenyl acetonitrile thus obtained with nicotinic ester in presence of alkali metal alkoxide and water immiscible organic solvent to produce ketonitrile, (iii) hydrolyzing followed by decarboxylating the said ketonitrile in situ to respective ketone in acid environment below 60° C, (iv) subjecting the ketone so obtained to reduction followed by N-oxidation, cyanation, and hydrolysis by any known methods to produce picolinic acid, (v) cyclising the said picolinic acid to tricyclic ketone by conventional methods, (vi) treating the said tricyclic ketone with organometallic compound containing Mg to produce carbinol, (viii) purifying the said carbinol with purifying agent selected from polar water miscible organic solvent followed by dehydrating with neat sulphuric acid at the temperature below 50° C, to get N-methyl product (olefin), and subjecting the said olefin to N-carbethoxylation to produce loratadine. Loratadine can also be prepared by treating cayano compound with organometallic compound containing Mg to produce a ketone by the methods known in the art followed by cyclising in presence of a mixture of sulfuric acid and a source of boric acid to get N-methyl product and converting to loratadine by N-carbethoxylation.