423165-08-6

Basic information

• Product Name: 3-(3-Isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane-p-toluenesulfonate
• Synonyms: 3-(3-Isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane-p-toluenesulfonate;3-(3-Isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]]octane 4-methylbenzenesulfonate;di-tert-butyl 4,4'-disulfanediyldipiperidine-1-carboxylate;3-(3-Isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane 4-methylbenzenesulfon
• CAS NO: 423165-08-6
• Molecular Formula: C₇H₈O₃S*C₁₃H₂₂N₄
• Molecular Weight: 406.5422
• Mol File: 423165-08-6.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 402.4 °C at 760 mmHg
• Flash Point: 197.1 °C
• Appearance: /
• Vapor Pressure: 1.1E-06mmHg at 25°C
• CAS DataBase Reference: 3-(3-Isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane-p-toluenesulfonate(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(3-Isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane-p-toluenesulfonate(423165-08-6)
• EPA Substance Registry System: 3-(3-Isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane-p-toluenesulfonate(423165-08-6)

Safety Data

• Hazardous Substances Data: 423165-08-6(Hazardous Substances Data)

Usage

InChI:InChI=1/C13H22N4.C7H8O3S/c1-8(2)13-16-15-9(3)17(13)12-6-10-4-5-11(7-12)14-10;1-6-2-4-7(5-3-6)11(8,9)10/h8,10-12,14H,4-7H2,1-3H3;2-5H,1H3,(H,8,9,10)

Synthetic route

exo-8-benzyl-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane (423165-13-3) + toluene-4-sulfonic acid (104-15-4) → exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen In methanol at 50℃; under 2250.23 Torr; Solvent; Time; Inert atmosphere; Large scale;	92%
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 2585.81 Torr; Inert atmosphere;	86%
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 6723.1 Torr; for 17h;	80%
With palladium 10% on activated carbon; hydrogen In methanol at 20℃;	80%

8-Benzyl-1αH,5αH-nortropan-3-one Oxime (76272-34-9) → exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6)

Conditions	Yield
Multi-step reaction with 8 steps 1: sodium; propan-1-ol / toluene / 12 h / Reflux; Inert atmosphere 2: tetrahydrofuran / 72 h / 20 °C / Inert atmosphere 3: hydrogenchloride / methanol; 1,4-dioxane / 2 h / 20 °C / Inert atmosphere 4: sodium carbonate / water; dichloromethane / 0 - 20 °C / Inert atmosphere 5: phosphorus pentachloride / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 6: dichloromethane; tert-Amyl alcohol / 0 - 20 °C / Inert atmosphere 7: acetic acid / ethyl acetate / 0.5 h / 80 °C / Inert atmosphere 8: palladium 10% on activated carbon; hydrogen / methanol / 20 °C / 2585.81 Torr / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: sodium / pentan-1-ol / 4 h / Reflux 2.1: sodium carbonate / dichloromethane / 2.5 h / 0 - 20 °C 3.1: phosphorus pentachloride; pyridine / dichloromethane / 4 h / 20 °C / Inert atmosphere; Cooling with ice 3.2: 17.5 h / 0 - 20 °C / Inert atmosphere 3.3: 2 h / Inert atmosphere; Reflux 4.1: palladium 10% on activated carbon; hydrogen / methanol / 20 °C View Scheme

8-benzyl-8-azabicyclo[3.2.1]octan-3-amine → exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6)

Conditions	Yield
Multi-step reaction with 7 steps 1: tetrahydrofuran / 72 h / 20 °C / Inert atmosphere 2: hydrogenchloride / methanol; 1,4-dioxane / 2 h / 20 °C / Inert atmosphere 3: sodium carbonate / water; dichloromethane / 0 - 20 °C / Inert atmosphere 4: phosphorus pentachloride / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 5: dichloromethane; tert-Amyl alcohol / 0 - 20 °C / Inert atmosphere 6: acetic acid / ethyl acetate / 0.5 h / 80 °C / Inert atmosphere 7: palladium 10% on activated carbon; hydrogen / methanol / 20 °C / 2585.81 Torr / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: sodium carbonate / dichloromethane / 2.5 h / 0 - 20 °C 2.1: phosphorus pentachloride; pyridine / dichloromethane / 4 h / 20 °C / Inert atmosphere; Cooling with ice 2.2: 17.5 h / 0 - 20 °C / Inert atmosphere 2.3: 2 h / Inert atmosphere; Reflux 3.1: palladium 10% on activated carbon; hydrogen / methanol / 20 °C View Scheme

exo-(8-benzyl-8-aza-bicyclo[3.2.1]oct-3-yl)-carbamic acid tert-butyl ester (132259-54-2) → exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6)

Conditions

Yield

Multi-step reaction with 6 steps 1: hydrogenchloride / methanol; 1,4-dioxane / 2 h / 20 °C / Inert atmosphere 2: sodium carbonate / water; dichloromethane / 0 - 20 °C / Inert atmosphere 3: phosphorus pentachloride / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 4: dichloromethane; tert-Amyl alcohol / 0 - 20 °C / Inert atmosphere 5: acetic acid / ethyl acetate / 0.5 h / 80 °C / Inert atmosphere 6: palladium 10% on activated carbon; hydrogen / methanol / 20 °C / 2585.81 Torr / Inert atmosphere View Scheme

N-((1R,3S,5S)-8-Benzyl-8-aza-bicyclo[3.2.1]oct-3-yl)-2-methyl-propionimidoyl chloride → exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: dichloromethane; tert-Amyl alcohol / 0 - 20 °C / Inert atmosphere 2: acetic acid / ethyl acetate / 0.5 h / 80 °C / Inert atmosphere 3: palladium 10% on activated carbon; hydrogen / methanol / 20 °C / 2585.81 Torr / Inert atmosphere View Scheme

8-benzyl-8-aza-bicyclo[3.2.1]oct-3-yl-amine (76272-36-1) → exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6)

Conditions

Yield

Multi-step reaction with 5 steps 1: sodium carbonate / water; dichloromethane / 0 - 20 °C / Inert atmosphere 2: phosphorus pentachloride / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 3: dichloromethane; tert-Amyl alcohol / 0 - 20 °C / Inert atmosphere 4: acetic acid / ethyl acetate / 0.5 h / 80 °C / Inert atmosphere 5: palladium 10% on activated carbon; hydrogen / methanol / 20 °C / 2585.81 Torr / Inert atmosphere View Scheme

exo-N-(8-benzyl-8-azabicyclo[3.2.1]oct-3-yl)-2-methylpropanamide (376348-67-3) → exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: phosphorus pentachloride / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 2: dichloromethane; tert-Amyl alcohol / 0 - 20 °C / Inert atmosphere 3: acetic acid / ethyl acetate / 0.5 h / 80 °C / Inert atmosphere 4: palladium 10% on activated carbon; hydrogen / methanol / 20 °C / 2585.81 Torr / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: phosphorus pentachloride; pyridine / dichloromethane / 4 h / 20 °C / Inert atmosphere; Cooling with ice 1.2: 17.5 h / 0 - 20 °C / Inert atmosphere 1.3: 2 h / Inert atmosphere; Reflux 2.1: palladium 10% on activated carbon; hydrogen / methanol / 20 °C View Scheme

N-benzylnortropinone (28957-72-4) → exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6)

Conditions	Yield
Multi-step reaction with 9 steps 1: hydroxylamine hydrochloride; sodium hydroxide / ethanol; water / 20 h / Inert atmosphere; Reflux 2: sodium; propan-1-ol / toluene / 12 h / Reflux; Inert atmosphere 3: tetrahydrofuran / 72 h / 20 °C / Inert atmosphere 4: hydrogenchloride / methanol; 1,4-dioxane / 2 h / 20 °C / Inert atmosphere 5: sodium carbonate / water; dichloromethane / 0 - 20 °C / Inert atmosphere 6: phosphorus pentachloride / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 7: dichloromethane; tert-Amyl alcohol / 0 - 20 °C / Inert atmosphere 8: acetic acid / ethyl acetate / 0.5 h / 80 °C / Inert atmosphere 9: palladium 10% on activated carbon; hydrogen / methanol / 20 °C / 2585.81 Torr / Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1.1: hydroxylamine hydrochloride; sodium hydrogencarbonate / water; ethanol / 2 h / Inert atmosphere 2.1: sodium / pentan-1-ol / 4 h / Reflux 3.1: sodium carbonate / dichloromethane / 2.5 h / 0 - 20 °C 4.1: phosphorus pentachloride; pyridine / dichloromethane / 4 h / 20 °C / Inert atmosphere; Cooling with ice 4.2: 17.5 h / 0 - 20 °C / Inert atmosphere 4.3: 2 h / Inert atmosphere; Reflux 5.1: palladium 10% on activated carbon; hydrogen / methanol / 20 °C View Scheme

(-)-(3S)-3-benzyloxycarbonylamino-3-phenylpropanal + exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6) → benzyl (S)-3-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropylcarbamate (376348-80-0)

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 20℃; Inert atmosphere;	93%

4,4-difluorocyclohexanecarboxylic acid (3-oxo-1-phenyl-propyl)-amide (376348-78-6) + exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6) → maraviroc (376348-65-1)

Conditions	Yield
With sodium tris(acetoxy)borohydride In ethyl acetate at 0 - 15℃; for 2h; Inert atmosphere; Large scale;	91%
With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 20℃; Inert atmosphere; optical yield given as %ee;	78%

exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6) + tert-butyl (1S)-3-oxo-1-phenylpropylcarbamate (135865-78-0) → tert-butyl (1S)-3-[3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-exo-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropylcarbamate (376348-70-8)

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In 1,2-dichloro-ethane at 0 - 20℃; for 3h; Inert atmosphere;	89%
With sodium tris(acetoxy)borohydride; acetic acid In 1,2-dichloro-ethane at 0 - 20℃; for 3h;	60%

(S)-benzyl 1-(naphthalen-2-yl)-3-oxopropylcarbamate (1255215-24-7) + exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6) → benzyl (S)-3-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-(naphthalen-2-yl)propylcarbamate (1255215-30-5)

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 20℃; Inert atmosphere;	71%

(S)-N-(3-oxo-1-phenylpropyl)cyclohexanecarboxamide (1255215-14-5) + exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6) → N-((S)-3-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropyl)cyclohexanecarboxamide (1255215-28-1)

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 20℃; Inert atmosphere;	63%

exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6) → C30H46N8O4 (1519003-85-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid; sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 3 h / 0 - 20 °C / Inert atmosphere 2: hydrogenchloride / methanol; 1,4-dioxane / 3 h / 20 °C / Inert atmosphere 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine / N,N-dimethyl-formamide / 3 h / 20 °C / Inert atmosphere View Scheme

exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6) → C55H81N9O8 (1519003-78-1)

Conditions

Yield

Multi-step reaction with 4 steps 1: acetic acid; sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 3 h / 0 - 20 °C / Inert atmosphere 2: hydrogenchloride / methanol; 1,4-dioxane / 3 h / 20 °C / Inert atmosphere 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine / N,N-dimethyl-formamide / 3 h / 20 °C / Inert atmosphere 4: 3-[4-[[bis[[1-(3-hydroxypropyl)triazol-4-yl]methyl]amino]methyl]triazol-1-yl]propan-1-ol; copper(II) sulfate; sodium L-ascorbate / tert-butyl alcohol / 2 h / 20 °C / Inert atmosphere View Scheme

exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6) → (S)-3-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropan-1-amine (376348-71-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid; sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 3 h / 0 - 20 °C 2: hydrogenchloride / water; methanol; 1,4-dioxane / 3 h / 20 °C View Scheme

exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6) → maraviroc (376348-65-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid; sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 3 h / 0 - 20 °C 2: hydrogenchloride / water; methanol; 1,4-dioxane / 3 h / 20 °C 3: sodium carbonate / water; dichloromethane / 0.5 h / 0 - 20 °C View Scheme

Upstream product

• 28957-72-4 N-benzylnortropinone 
• 376348-67-3 exo-N-(8-benzyl-8-azabicyclo[3.2.1]oct-3-yl)-2-methylpropanamide 
• 76272-36-1 8-benzyl-8-aza-bicyclo[3.2.1]oct-3-yl-amine 
• 132259-54-2 exo-(8-benzyl-8-aza-bicyclo[3.2.1]oct-3-yl)-carbamic acid tert-butyl ester 
• 76272-34-9 8-Benzyl-1αH,5αH-nortropan-3-one Oxime 
• 423165-13-3 exo-8-benzyl-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane 
• 104-15-4 toluene-4-sulfonic acid 

Downstream Products

• 376348-80-0 benzyl (S)-3-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropylcarbamate 
• 376348-65-1 maraviroc 
• 1255215-28-1 N-((S)-3-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropyl)cyclohexanecarboxamide 
• 1255215-29-2 benzyl (S)-1-(4-chlorophenyl)-3-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)propylcarbamate 
• 1255215-30-5 benzyl (S)-3-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-(naphthalen-2-yl)propylcarbamate 
• 376348-70-8 tert-butyl (1S)-3-[3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-exo-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropylcarbamate 
• 1519003-75-8 C₃₃H₅₂N₈O 
• 1519003-85-0 C₃₀H₄₆N₈O₄ 
• 1519003-78-1 C₅₅H₈₁N₉O₈ 
• 376348-71-9 (S)-3-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropan-1-amine 

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