169447-86-3

Basic information

• Product Name: (S)-1-Boc-2-benzylpiperazine
• Synonyms: (S)-1-Boc-2-Benzylpiperizine;(S)-1-BOC-2-BENZYL-PIPERAZINE 98%;(S)-2-Benzylpiperazine, N1-BOC protected;(S)-tert-Butyl 2-benzylpiperazine-1-carboxylate;1-Piperazinecarboxylic acid, 2-(phenylmethyl)-, 1,1-dimethylethyl ester, (2S)-;(S)-1-N-Boc-2-Benzylpiperazine ,98%;(S)-2-Benzyl-1-Boc-piperazine;tert-butyl (2S)-2-benzylpiperazine-1-carboxylate
• CAS NO: 169447-86-3
• Molecular Formula: C₁₆H₂₄N₂O₂
• Molecular Weight: 276.37
• Product Categories: Piperaizine
• Mol File: 169447-86-3.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 382.9°C at 760 mmHg
• Flash Point: 185.4°C
• Appearance: /
• Density: 1.066g/cm³
• Vapor Pressure: 4.58E-06mmHg at 25°C
• Refractive Index: 1.524
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 8.45±0.40(Predicted)
• CAS DataBase Reference: (S)-1-Boc-2-benzylpiperazine(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-1-Boc-2-benzylpiperazine(169447-86-3)
• EPA Substance Registry System: (S)-1-Boc-2-benzylpiperazine(169447-86-3)

Safety Data

• Hazard Codes: Xi
• Hazardous Substances Data: 169447-86-3(Hazardous Substances Data)

Usage

General Description

(S)-1-Boc-2-benzylpiperazine is a chemical compound with the molecular formula C18H26N2O2. It is a derivative of piperazine and has a Boc (tert-butoxycarbonyl) protecting group at the N1 position and a benzyl group at the N2 position. (S)-1-Boc-2-benzylpiperazine is used in organic synthesis as a building block for the preparation of various pharmaceutical and biologically active molecules. It is also commonly used as a precursor in the synthesis of drugs targeting the central nervous system, such as antidepressants and antipsychotics. Additionally, (S)-1-Boc-2-benzylpiperazine has potential applications in medicinal chemistry and drug discovery due to its favorable pharmacokinetic and pharmacodynamic properties.

InChI:InChI=1/C16H24N2O2/c1-16(2,3)20-15(19)18-10-9-17-12-14(18)11-13-7-5-4-6-8-13/h4-8,14,17H,9-12H2,1-3H3/t14-/m0/s1

Synthetic route

(S)-tert-butyl 2,4-dibenzylpiperazine-1-carboxylate → tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3)

Conditions	Yield
With palladium 10% on activated carbon In methanol at 20℃; for 12h;	99%

1-tert-Butoxycarbonyl-2(S)-(S),4-dibenzylpiperazine (489437-72-1) → tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3)

Conditions	Yield
palladium
palladium

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: methanol / 0.5 h / 20 °C 1.2: 6 h / 20 °C 2.1: acetic acid / 2 h / 160 °C / Sealed tube 3.1: lithium aluminium tetrahydride / tetrahydrofuran / 2 h / 0 - 20 °C 4.1: triethylamine / dichloromethane / 18 h / 20 °C 5.1: palladium 10% on activated carbon / methanol / 12 h / 20 °C View Scheme

(3S)-1,3-dibenzylpiperazine-2,5-dione (169447-84-1) → tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 2 h / 0 - 20 °C 2: triethylamine / dichloromethane / 18 h / 20 °C 3: palladium 10% on activated carbon / methanol / 12 h / 20 °C View Scheme

C27H37N3O4 → tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: acetic acid / 2 h / 160 °C / Sealed tube 2: lithium aluminium tetrahydride / tetrahydrofuran / 2 h / 0 - 20 °C 3: triethylamine / dichloromethane / 18 h / 20 °C 4: palladium 10% on activated carbon / methanol / 12 h / 20 °C View Scheme

(3S)-1,3-dibenzylpiperazine (204327-96-8) → tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: palladium 10% on activated carbon / methanol / 12 h / 20 °C View Scheme

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) + 2,2,2-trichloro-N-(isoquinolin-5-yl)acetamide (581812-64-8) → C26H30N4O3 (1036740-32-5)

Conditions	Yield
With triethylamine In tetrahydrofuran	39%

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) + 2-amino-3,5-dibromopyrazine (24241-18-7) → 2-amino-5-bromo-3-[(S)-4-Boc-3-benzylpiperazinyl]pyrazine (956006-04-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1,4-dioxane; α,α,α-trifluorotoluene at 210℃; for 0.333333h; Microwave irradiation;

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) + 2,6-dichloropyrazine (4774-14-5) → C20H25ClN4O2 (956006-14-7)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1,4-dioxane; α,α,α-trifluorotoluene at 180℃; for 0.333333h;

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) + 5-iso-butyl-6-(3-iso-butyl-1H-pyrazol-5-yl)pyridazine-3-carboxylic acid → tert-butyl (S)-2-benzyl-4-[5-iso-butyl-6-(3-iso-butyl-1H-pyrazol-5-yl)pyridazine-3-carbonyl]piperazine-1-carboxylate (952591-36-5)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) + C19H20O2N4 → tert-butyl (S)-2-benzyl-4-[6-(3-benzyl-1H-pyrazol-5-yl)-5-iso-butylpyridazine-3-carbonyl]piperazine-1-carboxylate (952591-38-7)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) + 4-iso-butyl-6-(2-iso-propylphenyl)pyridazine-3-carboxylic acid (952591-53-6) → tert-butyl (S)-2-benzyl-4-[4-iso-butyl-6-(2-iso-propylphenyl)pyridazine-3-carbonyl]piperazine-1-carboxylate (952591-54-7)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) + 5-iso-butyl-6-(6-iso-butylpyrimidin-4-yl)pyridazine-3-carboxylic acid → C33H44O3N6

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) → C29H36ON4

Conditions	Yield
Multi-step reaction with 2 steps 1: EDCl; HOBt; DIPEA / CH2Cl2 / 20 °C 2: TFA / CH2Cl2 / 1 h / 20 °C View Scheme

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) → (S)-1-(2-benzyl-4-(4-iso-butyl-6-(2-iso-propylphenyl)pyridazine-3-carbonyl)piperazin-1-yl)ethanone

Conditions	Yield
Multi-step reaction with 3 steps 1: EDCl; HOBt; DIPEA / CH2Cl2 / 20 °C 2: TFA / CH2Cl2 / 1 h / 20 °C 3: TEA / acetonitrile / 20 °C View Scheme

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) + C12H10ClN5O + C12H10ClN5O + C12H9Cl2N5O + C12H9Cl2N5O → 3-(3-methyl-1H-indazol-5-yl)-5-[(S)-4-Boc-3-benzylpiperazin-1-yl]-[1,2,4]triazine + 6-chloro-3-(3-methyl-1H-indazol-5-yl)-5-[(S)-4-Boc-3-benzylpiperazin-1-yl]-[1,2,4]triazine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 60℃; for 1h;

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) + isoquinoline-5-carboxylic acid (27810-64-6) → C26H29N3O3 (1036739-94-2)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) + 5-bromoisoquinoline (34784-04-8) → C25H29N3O2 (1036739-50-0)

Conditions	Yield
With caesium carbonate; tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 120℃; for 18h; Hartwig Buchwald amination;

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) + Benzofuran-2-carboxylic acid (496-41-3) → C25H28N2O4

Conditions	Yield
With 2,6-dimethylpyridine; 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) + 6-(3-benzyl-1H-pyrazol-5-yl)-5-iso-butylpyridazine-3-carboxylic acid → tert-butyl (S)-2-benzyl-4-[5-iso-butyl-6-(3-iso-butyl-1H-pyrazol-5-yl)pyridazine-3-carbonyl]piperazine-1-carboxylate (952591-36-5)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) → 2-[(S)-3-benzylpiperazinyl]-6-[3-methyl-1H-indazol-5-yl]pyrazine

Conditions	Yield
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / 1,4-dioxane; α,α,α-trifluorotoluene / 0.33 h / 180 °C 2: sodium carbonate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 0.25 h / 140 °C / Microwave irradiation 3: water; trifluoroacetic acid / 16 h / 20 °C View Scheme

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) → 2-amino-3-[(S)-3-benzylpiperazinyl]-5-(3-methyl-1H-indazol-5-yl)pyrazine

Conditions	Yield
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / 1,4-dioxane; α,α,α-trifluorotoluene / 0.33 h / 210 °C / Microwave irradiation 2: triethylamine / tris-(dibenzylideneacetone)dipalladium(0); tris-(o-tolyl)phosphine / N,N-dimethyl-formamide / 0.17 h / 120 °C / Microwave irradiation 3: hydrogenchloride / 1,4-dioxane; dichloromethane / 1 h / 20 °C View Scheme

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) → 2-amino-3-[(S)-4-Boc-3-benzylpiperazinyl]-5-(3-methyl-1H-indazol-5-yl)pyrazine (956006-06-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / 1,4-dioxane; α,α,α-trifluorotoluene / 0.33 h / 210 °C / Microwave irradiation 2: triethylamine / tris-(dibenzylideneacetone)dipalladium(0); tris-(o-tolyl)phosphine / N,N-dimethyl-formamide / 0.17 h / 120 °C / Microwave irradiation View Scheme

tert-butyl (S)-2-benzylpiperazine-1-carboxylate (169447-86-3) → 2-[(S)-4-Boc-3-benzylpiperazinyl]-6-[3-methyl-1-(2-(trimethylsilyl)ethoxymethyl)-1H-indazol-5-yl]pyrazine (956006-16-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / 1,4-dioxane; α,α,α-trifluorotoluene / 0.33 h / 180 °C 2: sodium carbonate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 0.25 h / 140 °C / Microwave irradiation View Scheme

Upstream product

• 204327-96-8 (3S)-1,3-dibenzylpiperazine 
• 169447-84-1 (3S)-1,3-dibenzylpiperazine-2,5-dione 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 489437-72-1 1-tert-Butoxycarbonyl-2(S)-(S),4-dibenzylpiperazine 

Downstream Products

• 956006-14-7 C₂₀H₂₅ClN₄O₂ 
• 956006-04-5 2-amino-5-bromo-3-[(S)-4-Boc-3-benzylpiperazinyl]pyrazine 
• 956006-16-9 2-[(S)-4-Boc-3-benzylpiperazinyl]-6-[3-methyl-1-(2-(trimethylsilyl)ethoxymethyl)-1H-indazol-5-yl]pyrazine 
• 956006-06-7 2-amino-3-[(S)-4-Boc-3-benzylpiperazinyl]-5-(3-methyl-1H-indazol-5-yl)pyrazine 
• 952591-36-5 tert-butyl (S)-2-benzyl-4-[5-iso-butyl-6-(3-iso-butyl-1H-pyrazol-5-yl)pyridazine-3-carbonyl]piperazine-1-carboxylate 
• 1036740-32-5 C₂₆H₃₀N₄O₃ 
• 1036739-50-0 C₂₅H₂₉N₃O₂ 
• 1036739-94-2 C₂₆H₂₉N₃O₃ 
• 952591-54-7 tert-butyl (S)-2-benzyl-4-[4-iso-butyl-6-(2-iso-propylphenyl)pyridazine-3-carbonyl]piperazine-1-carboxylate 
• 952591-38-7 tert-butyl (S)-2-benzyl-4-[6-(3-benzyl-1H-pyrazol-5-yl)-5-iso-butylpyridazine-3-carbonyl]piperazine-1-carboxylate 

Relevant articles and documents

Efficient one-pot synthesis of enantiomerically pure: N -protected-α-substituted piperazines from readily available α-amino acids

A new pathway towards enantiomerically pure 3-substituted piperazines, bearing a benzyl protecting group, has been developed in good overall yields (83-92%), starting from commercially available N-protected amino acids. The methodology represents an efficient and simple one-pot procedure, employing a synthetic sequence consisting of an Ugi-4 component reaction, a Boc-deprotection, an intramolecular cyclisation reaction and a final reduction (UDCR). From the benzyl protected precursors, the 2-substituted piperazines bearing a Boc-protecting group could consequently also be obtained via a simple protection and deprotection step of the corresponding piperazines. The practical utility of this methodology was demonstrated for chiral drug synthesis.

Inhibitors of farnesyl-protein transferase

The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras. The compounds of formula A are representative of the compounds of the present invention: STR1