147116-67-4

Basic information

• Product Name: (2S,3S)-2-Benzhydryl-N-(5-tert-butyl-2-Methoxybenzyl)quinuclidin-3-aMine
• Synonyms: (2S,3S)-2-Benzhydryl-N-(5-tert-butyl-2-Methoxybenzyl)quinuclidin-3-aMine;(2S-cis)-N-[[5-(1,1-DiMethylethyl)-2-Methoxyphenyl]Methyl]-2-(diphenylMethyl)-1-azabicyclo[2.2.2]octan-3-aMine;Maropitant;(2S,3S)-2-(Diphenylmethyl)-N-[2-methoxy-5-(2-methyl-2-propanyl)benzyl]quinuclidin-3-amine
• CAS NO: 147116-67-4
• Molecular Formula: C₃₂H₄₀N₂O
• Molecular Weight: 468.6728
• Product Categories: Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 147116-67-4.mol

Chemical Properties

• Boiling Point: 572.6°C at 760 mmHg
• Flash Point: 300.1°C
• Appearance: /
• Density: 1.11±0.1 g/cm3(Predicted)
• Vapor Pressure: 4.05E-13mmHg at 25°C
• PKA: 9.99±0.70(Predicted)
• CAS DataBase Reference: (2S,3S)-2-Benzhydryl-N-(5-tert-butyl-2-Methoxybenzyl)quinuclidin-3-aMine(CAS DataBase Reference)
• NIST Chemistry Reference: (2S,3S)-2-Benzhydryl-N-(5-tert-butyl-2-Methoxybenzyl)quinuclidin-3-aMine(147116-67-4)
• EPA Substance Registry System: (2S,3S)-2-Benzhydryl-N-(5-tert-butyl-2-Methoxybenzyl)quinuclidin-3-aMine(147116-67-4)

Safety Data

• Hazardous Substances Data: 147116-67-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(2S,3S)-2-Benzhydryl-N-(5-tert-butyl-2-Methoxybenzyl)quinuclidin-3-aMine is used as a pharmaceutical compound for its potential therapeutic effects. The compound's unique structure allows it to interact with specific biological targets, making it a candidate for the development of new drugs.
Used in Anesthetic Applications:
In the field of anesthesiology, (2S,3S)-2-Benzhydryl-N-(5-tert-butyl-2-Methoxybenzyl)quinuclidin-3-aMine has been shown to decrease anesthetic requirements during visceral stimulation. This property could be beneficial in reducing the amount of anesthesia needed for certain surgical procedures, potentially leading to fewer side effects and a quicker recovery for patients.
Used in Drug Delivery Systems:
Similar to gallotannin, (2S,3S)-2-Benzhydryl-N-(5-tert-butyl-2-Methoxybenzyl)quinuclidin-3-aMine may also be employed in drug delivery systems. By incorporating (2S,3S)-2-Benzhydryl-N-(5-tert-butyl-2-Methoxybenzyl)quinuclidin-3-aMine into various carriers, such as organic or metallic nanoparticles, its delivery, bioavailability, and therapeutic outcomes could be improved, enhancing its overall effectiveness in treating specific conditions.

InChI:InChI=1/C32H40N2O.C6H8O7.H2O/c1-32(2,3)27-15-16-28(35-4)26(21-27)22-33-30-25-17-19-34(20-18-25)31(30)29(23-11-7-5-8-12-23)24-13-9-6-10-14-24;7-3(8)1-6(13,5(11)12)2-4(9)10;/h5-16,21,25,29-31,33H,17-20,22H2,1-4H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12);1H2/t30-,31-;;/m0../s1

Synthetic route

(2S,3R)-2-diphenylmethyl-3-methanesulfonyloxyquinuclidine + 2-methoxy-5-tert-butylbenzylamine → (2S,3S)-N-(5-tert-butyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine (147116-67-4)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 100℃;	87.1%

2-(bromomethyl)-4-(tert-butyl)-1-methoxybenzene (911060-73-6) + (-)-(2S,3S)-cis-2-(diphenylmethyl)-1-azabicyclo[2.2.2]octane-3-amine (142035-23-2) → (2S,3S)-N-(5-tert-butyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine (147116-67-4)

Conditions	Yield
With dmap; triethylamine In N,N-dimethyl-formamide at 0 - 30℃;	85.3%

2-methoxy-5-tert-butylbenzylamine + (2S,3R)-2-diphenylmethyl-3-trifluoromethanesulfonyloxyquinuclidine → (2S,3S)-N-(5-tert-butyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine (147116-67-4)

Conditions	Yield
With dmap In 2-methyltetrahydrofuran Reflux;	82.6%

2-chloromethyl-4-tert-butylanisole (22252-73-9) + (-)-(2S,3S)-cis-2-(diphenylmethyl)-1-azabicyclo[2.2.2]octane-3-amine (142035-23-2) → (2S,3S)-N-(5-tert-butyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine (147116-67-4)

Conditions	Yield
With dmap; caesium carbonate In 1,4-dioxane at 80℃; for 24h;	64.9%

(2S,3S)-2-benzhydryl-N-(5-tert-butyl-2-methoxybenzyl)quinuclidin-3-amine (1R)-10-camphorsulfonate (862543-52-0) → (2S,3S)-N-(5-tert-butyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine (147116-67-4)

Conditions	Yield
With sodium hydroxide; water In isopropyl alcohol; toluene at 20 - 25℃; pH=12.5 - 12.9;

methyl 3-oxoquinuclidine-2-carboxylate → (2S,3S)-N-(5-tert-butyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine (147116-67-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: methanol / 5 h / Reflux 2: tetrahydrofuran / 2 h / 0 - 20 °C / Inert atmosphere 3: titanium(IV) isopropylate; 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 24 h / Inert atmosphere 4: 5%-palladium/activated carbon; hydrogen / isopropyl alcohol / 24 h / 80 °C / Inert atmosphere 5: triethylamine; dmap / N,N-dimethyl-formamide / 0 - 30 °C View Scheme
Multi-step reaction with 5 steps 1: methanol / 5 h / Reflux 2: tetrahydrofuran / 2 h / 0 - 20 °C / Inert atmosphere 3: titanium(IV) isopropylate; 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 24 h / Inert atmosphere 4: 5%-palladium/activated carbon; hydrogen / isopropyl alcohol / 24 h / 80 °C / Inert atmosphere 5: dmap; caesium carbonate / 1,4-dioxane / 24 h / 80 °C View Scheme

methyl 4-azaspiro[bicyclo[2.2.2]octane-2,2'-[1,3]dioxolane]-3-carboxylate → (2S,3S)-N-(5-tert-butyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine (147116-67-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: tetrahydrofuran / 2 h / 0 - 20 °C / Inert atmosphere 2: titanium(IV) isopropylate; 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 24 h / Inert atmosphere 3: 5%-palladium/activated carbon; hydrogen / isopropyl alcohol / 24 h / 80 °C / Inert atmosphere 4: triethylamine; dmap / N,N-dimethyl-formamide / 0 - 30 °C View Scheme
Multi-step reaction with 4 steps 1: tetrahydrofuran / 2 h / 0 - 20 °C / Inert atmosphere 2: titanium(IV) isopropylate; 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 24 h / Inert atmosphere 3: 5%-palladium/activated carbon; hydrogen / isopropyl alcohol / 24 h / 80 °C / Inert atmosphere 4: dmap; caesium carbonate / 1,4-dioxane / 24 h / 80 °C View Scheme

2-(diphenylmethylen)quinuclidin-3-one → (2S,3S)-N-(5-tert-butyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine (147116-67-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: titanium(IV) isopropylate; 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 24 h / Inert atmosphere 2: 5%-palladium/activated carbon; hydrogen / isopropyl alcohol / 24 h / 80 °C / Inert atmosphere 3: triethylamine; dmap / N,N-dimethyl-formamide / 0 - 30 °C View Scheme
Multi-step reaction with 3 steps 1: titanium(IV) isopropylate; 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 24 h / Inert atmosphere 2: 5%-palladium/activated carbon; hydrogen / isopropyl alcohol / 24 h / 80 °C / Inert atmosphere 3: dmap; caesium carbonate / 1,4-dioxane / 24 h / 80 °C View Scheme

(2S,3S)-2-diphenylmethyl-N-((S)-1-phenylethyl)quinuclidin-3-amine → (2S,3S)-N-(5-tert-butyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine (147116-67-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 5%-palladium/activated carbon; hydrogen / isopropyl alcohol / 24 h / 80 °C / Inert atmosphere 2: triethylamine; dmap / N,N-dimethyl-formamide / 0 - 30 °C View Scheme

(S)-2-diphenylmethylquinuclidin-3-one (683206-53-3) → (2S,3S)-N-(5-tert-butyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine (147116-67-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium; isopropyl alcohol / toluene / 1.5 h / Reflux 2: pyridine / dichloromethane / 7 h / 5 °C / Reflux 3: triethylamine / N,N-dimethyl-formamide / 100 °C View Scheme
Multi-step reaction with 3 steps 1: sodium; isopropyl alcohol / toluene / 1.5 h / Reflux 2: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 24 h / 5 - 20 °C 3: dmap / 2-methyltetrahydrofuran / Reflux View Scheme

(+)-(2S,3R)-2-(diphenylmethyl)-1-azabicyclo<2.2.2>octan-3-ol → (2S,3S)-N-(5-tert-butyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine (147116-67-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / dichloromethane / 7 h / 5 °C / Reflux 2: triethylamine / N,N-dimethyl-formamide / 100 °C View Scheme

(2-diphenylmethyl-1-azabicyclo[2.2.2]oct-3-yl)-benzylamine + 5-tert-butyl-2-methoxybenzaldehyde (85943-26-6) → (2S,3S)-N-(5-tert-butyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine (147116-67-4)

Conditions	Yield
Stage #1: (2-diphenylmethyl-1-azabicyclo[2.2.2]oct-3-yl)-benzylamine With hydrogen; acetic acid In water; isopropyl alcohol at 75℃; for 12h; Stage #2: 5-tert-butyl-2-methoxybenzaldehyde In water; isopropyl alcohol at 75℃; Cooling; Stage #3: With palladium on activated charcoal; hydrogen In water; isopropyl alcohol at 40℃; for 12h;

(2S,3S)-N-(5-tert-butyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine (147116-67-4) + citric acid (77-92-9) → (2S,3S)-2-benzhydryl-N-(5-tert-butyl-2-methoxybenzyl)quinuclidin-3-amine citrate monohydrate (359875-09-5)

Conditions	Yield
With water In acetone at 38 - 42℃;

Upstream product

• 85943-26-6 5-tert-butyl-2-methoxybenzaldehyde 
• 683206-53-3 (S)-2-diphenylmethylquinuclidin-3-one 
• 1226409-70-6 2-methoxy-5-tert-butylbenzylamine 
• 22252-73-9 2-chloromethyl-4-tert-butylanisole 
• 142035-23-2 (-)-(2S,3S)-cis-2-(diphenylmethyl)-1-azabicyclo[2.2.2]octane-3-amine 
• 911060-73-6 2-(bromomethyl)-4-(tert-butyl)-1-methoxybenzene 
• 1219175-35-5 methyl 3-oxoquinuclidine-2-carboxylate 
• 862543-52-0 (2S,3S)-2-benzhydryl-N-(5-tert-butyl-2-methoxybenzyl)quinuclidin-3-amine (1R)-10-camphorsulfonate 

Downstream Products

• 862543-54-2 maropitant citrate 
• 359875-09-5 maropitant citrate monohydrate 

Relevant articles and documents

Crystal form of maropitant free alkali and preparation method thereof

The invention relates to a crystal form of maropitant free alkali and a preparation method of the crystal form, the characteristic peaks of an X-ray powder diffraction pattern of the crystal form arerepresented by 2[theta] (+/-0.2 degree 2[theta]), and the characteristic peaks are 6.25 degrees, 8.27 degrees, 16.54 degrees and 16.62 degrees.

Preparation method of maropitant free alkali

The invention relates to a preparation method of maropitant free alkali. The reaction of the preparation method relates to a reaction between (2S,3R)-2-benzhydryl quinuclidine-3-alcohol and R1SO2Cl or(CF2SO2)2O; by means of the reaction, a hydroxyl protected compound formula IV can be obtained; the formula IV can react with 2-methoxy-5-tert butyl-benzylamine under the existence of an alkali and asolvent to obtain the maropitant free alkali. (The formula is shown in the description).

Method for preparing maropitant free alkali

The invention relates to a method for preparing maropitant free alkali. A reaction formula is as shown in the specification.

PROCESS FOR PREPARATION OF 1-(2S,3S)-2-BENZHYDR YL-N-(5-TERT-BUTYL-2-METHOXYBENZYL)QUINUCLIDIN-3-AMINE

This invention relates to an improved process for the preparation of (2S,3S)-- 2-benzhydryl-N-(5-tent-butyl-2-methoxybenzyl)quinuclidin-3-amine, (hereinafter "compound of Formula I") and its pharmaceutically acceptable salts. In particular, the invention is directed to an improved synthesis of the monohydrate citrate salt of the compound of Formula (la).

Pharmaceutical composition and method of modulating cholinergic function in a mammal

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NK-1 RECEPTOR ANTAGONISTS FOR THE TREATMENT OF NEURONAL INJURY AND STROKE

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NK-1 RECEPTOR ANTAGONISTS FOR THE TREATMENT OF SYMPTOMS OF IRRITABLE BOWEL SYNDROME

The present invention relates to a method of treating or preventing symptoms of irritable bowel syndrome in a mammal, including a human, using a compound that is an NK-1 receptor antagonist, in particular a substance P receptor antagonist.

QUINUCLIDINE DERIVATIVES

Compounds of the formula STR1 wherein R 1 is methoxy and R. sup.2 is selected from the group consisting of methyl, ethyl, isopropyl, sec-butyl and tert-butyl; and the pharmaceutically acceptable salts of such compounds.These compounds are substance P antagonists and useful in the treatment of gastrointestinal disorders, inflammatory disorders, central nervous system disorders and pain.

QUINUCLIDINE DERIVATIVES

Compounds of the formula STR1 wherein R 1 is methoxy and R. sup.2 is selected from the group consisting of methyl, ethyl, isopropyl, sec-butyl and tert-butyl; and the pharmaceutically acceptable salts of such compounds.These compounds are substance P antagonists and useful in the treatment of gastrointestinal disorders, inflammatory disorders, central nervous system disorders and pain.

The use of certain NK-1 receptor antagonists for the manufacture of a medicament for treating emesis

The use of a compound of the formula: - (2S,3S)-3-(2-methoxy-5-trifluoromethoxybenzyl)amino-2-phenylpiperidine; (2S,3S)-N-(5-tert-butyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo-[2.2.2]octan-3-amine; or (2S,3S)-N-(5-isopropyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo-[2.2.2]octan-3-amine; or of a pharmaceutically acceptable salt of one of the foregoing compounds, for the manufacture of a medicament for preventing or treating delayed emesis in a mammal.