130642-50-1

Basic information

• Product Name: Loratadine ketone
• Synonyms: (1-METHYL-4-PIPERIDINYL) {3[2-(3-CHLOROPHENYL) ETHYL ]2-PYRIDINYL} METHANONE =98%;(3-(3-chlorophenethyl)pyridin-2-yl)(1-Methylpiperidin-4-yl)Methanone;1-(METHYL-4-PIPERIDINYL) [3(2)-(3-CHLOROPHENYL) ETHYL 2-PYRIDINYL] METHANONE;loratadine ketone;{3-[2-(3-Chlorophenyl)-Ethyl]-2-Pyridinyl}-(1-Methyl-4-Piperidinyl)-Methanone;(1-Methyl-4-Piperidinyl) [3-[2-(3-Chlorophenyl)Ethyl]-2-Pyridinyl]Methanone HCl;{3-[2-(3-CHLORO-PHENYL)-ETHYL]-PYRIDIN-2-YL}-(1-METHYL-PIPERIDIN-4-YL)-METHANONE
• CAS NO: 130642-50-1
• Molecular Formula: C₂₀H₂₃ClN₂O
• Molecular Weight: 342.86242
• Mol File: 130642-50-1.mol
• Article Data: 2

Chemical Properties

• Melting Point: 179-186°C
• Boiling Point: 462.0±45.0 °C(Predicted)
• Appearance: /
• Density: 1.169±0.06 g/cm3(Predicted)
• PKA: 8.18±0.10(Predicted)
• CAS DataBase Reference: Loratadine ketone(CAS DataBase Reference)
• NIST Chemistry Reference: Loratadine ketone(130642-50-1)
• EPA Substance Registry System: Loratadine ketone(130642-50-1)

Safety Data

• Hazardous Substances Data: 130642-50-1(Hazardous Substances Data)

Usage

Uses

[3-[2-(3-Chlorophenyl)ethyl]-2-pyridinyl](1-methyl-4-piperidinyl)methanone is an impurity of Loratadine (L469575), a nonsedating-type histamine H1-receptor.

Synthetic route

3-[2-(3-chlorophenyl)ethyl]-2-pyridine-carbonitrile (31255-57-9) + (1-methyl-4-piperidyl)magnesium chloride (63463-36-5) → {3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1)

Conditions	Yield
With hydrogenchloride 1.) THF, reflux; Multistep reaction;
In pyridine

N-tert-butyl-3-methylpyridine-2-carboxamide (32998-95-1) → {3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) n-BuLi / 1.) THF, -40 deg C 2: POCl3 / Heating 3: 2.) aq. HCl / 1.) THF, reflux View Scheme

3-<2-(3-chlorophenyl)ethyl>-N-(1,1-dimethylethyl)-2-pyridinecarboxamide (107285-30-3) → {3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: POCl3 / Heating 2: 2.) aq. HCl / 1.) THF, reflux View Scheme

1-Chloro-3-chloromethyl-benzene (620-20-2) → {3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) n-BuLi / 1.) THF, -40 deg C 2: POCl3 / Heating 3: 2.) aq. HCl / 1.) THF, reflux View Scheme

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → {3-[2-(3-chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanol (170727-67-0)

Conditions	Yield
With sodium tetrahydroborate In ethanol for 3h;	99%

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → N-methyldesloratadine (38092-89-6)

Conditions	Yield
With trifluorormethanesulfonic acid Heating;

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → 10-chloro-11-(1-methyl-piperidin-4-yl)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (244122-88-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 99 percent / naBH4 / ethanol / 3 h 2: 3 percent / PPA / 3 h / 170 - 175 °C View Scheme

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → 8-chloro-11-(1-methyl-piperidin-4-yl)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (170727-68-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 99 percent / naBH4 / ethanol / 3 h 2: 5 percent / PPA / 3 h / 170 - 175 °C View Scheme

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → 1-[4-(10-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-piperidin-1-yl]-ethanone

Conditions	Yield
Multi-step reaction with 4 steps 1: 99 percent / naBH4 / ethanol / 3 h 2: 3 percent / PPA / 3 h / 170 - 175 °C 3: NEt3 / benzene / 1.5 h / Heating 4: 1.) Zn dust, AcOH / 1.) 80-100 deg C, 1 h, 2.) CH2Cl2, reflux, 1 h View Scheme

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → 1-[4-(8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-piperidin-1-yl]-ethanone

Conditions	Yield
Multi-step reaction with 4 steps 1: 99 percent / naBH4 / ethanol / 3 h 2: 5 percent / PPA / 3 h / 170 - 175 °C 3: NEt3 / benzene / 1.5 h / Heating 4: 1.) Zn dust, AcOH / 1.) 80-100 deg C, 1 h, 2.) CH2Cl2, reflux, 1 h View Scheme

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → 4-(8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-piperidine-1-carboxylic acid 2,2,2-trichloro-ethyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1: 99 percent / naBH4 / ethanol / 3 h 2: 5 percent / PPA / 3 h / 170 - 175 °C 3: NEt3 / benzene / 1.5 h / Heating View Scheme

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → 4-(10-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-piperidine-1-carboxylic acid 2,2,2-trichloro-ethyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1: 99 percent / naBH4 / ethanol / 3 h 2: 3 percent / PPA / 3 h / 170 - 175 °C 3: NEt3 / benzene / 1.5 h / Heating View Scheme

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → descarboethoxyloratadine (100643-71-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: CF3SO3H / Heating 2: Et3N / toluene / Heating 3: aq. KOH / Heating View Scheme

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → N-formyldesloratadine (117810-61-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: CF3SO3H / Heating 2: Et3N / toluene / Heating 3: aq. KOH / Heating 4: C5H5N / CH2Cl2 View Scheme

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → N-acetyl desloratadine (117796-52-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: CF3SO3H / Heating 2: Et3N / toluene / Heating 3: aq. KOH / Heating 4: C5H5N / CH2Cl2 View Scheme

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → 1-[4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidin-1-yl]propan-1-one (117796-54-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: CF3SO3H / Heating 2: Et3N / toluene / Heating 3: aq. KOH / Heating 4: C5H5N / CH2Cl2 View Scheme

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → 1-[4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidin-1-yl]butan-1-one (117810-98-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: CF3SO3H / Heating 2: Et3N / toluene / Heating 3: aq. KOH / Heating 4: C5H5N / CH2Cl2 View Scheme

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → 8-chloro-11-(1-trimethylacetyl-4-piperidylidene)-6,11-dihydro-5H-benzo-[5,6]cyclohepta[1,2-b]pyridine (117810-93-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: CF3SO3H / Heating 2: Et3N / toluene / Heating 3: aq. KOH / Heating 4: C5H5N / CH2Cl2 View Scheme

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → loratadine (79794-75-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: CF3SO3H / Heating 2: Et3N / toluene / Heating View Scheme

{3-[2-(3-Chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanone (130642-50-1) → 8-chloro-11-(1-benzoyl-4-piperidylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (117810-92-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: CF3SO3H / Heating 2: Et3N / toluene / Heating 3: aq. KOH / Heating 4: C5H5N / CH2Cl2 View Scheme

Upstream product

• 620-20-2 1-Chloro-3-chloromethyl-benzene 
• 107285-30-3 3-<2-(3-chlorophenyl)ethyl>-N-(1,1-dimethylethyl)-2-pyridinecarboxamide 
• 32998-95-1 N-tert-butyl-3-methylpyridine-2-carboxamide 
• 31255-57-9 3-[2-(3-chlorophenyl)ethyl]-2-pyridine-carbonitrile 
• 63463-36-5 (1-methyl-4-piperidyl)magnesium chloride 

Downstream Products

• 79794-75-5 loratadine 
• 117796-52-8 N-acetyl desloratadine 
• 117810-61-4 N-formyldesloratadine 
• 100643-71-8 descarboethoxyloratadine 
• 170727-67-0 {3-[2-(3-chloro-phenyl)-ethyl]-pyridin-2-yl}-(1-methyl-piperidin-4-yl)-methanol 
• 38092-89-6 N-methyldesloratadine 

Relevant articles and documents

Conformational considerations in the design of dual antagonists of platelet-activating factor (PAF) and histamine

Following the discovery of the first dual antagonist of platelet-activating factor (PAF) and histamine, 1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine, Sch 37370, 1, a related series of structures, exemplified by (±)-1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]-cyclohepta[1,2-b]pyridin-11-yl)piperazine, Sch 40338, 2, were prepared. Interestingly, the compounds exhibited a parallel structure-antiallergy activity relationship, suggesting that the two series may adopt a common conformation at the PAF receptor. Conformational analysis led to a proposal for this bioactive conformation accessible to both series. The synthesis of novel conformationally constrained analogues that might mimic the proposed bioactive conformation of these compounds, and the evaluation of their in vitro antiallergy activity form the subject matter of this report. Copyright (C) 1999 Elsevier Science Ltd.