116169-90-5

Basic information

• Product Name: N2-(1S-Ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine
• Synonyms: N2-(S)-1-Ethoxycarbonyl-3-phenylpropyl-N8-trifluoroacetyl-L-lysine;N2-(1S-Ethoxycarbonyl-3-phenyl;AABBAMEE;N2-((1,S)-ETHOXYCARBONYL-3-PHENYLPROPYL)-N-TRIFLUOROACETYL-2-LYSINE;[S-(R*,R*)]-α-[[1-Carboxy-5-[(trifluoroacetyl)amino]pentyl]amino]-benzenebutanoic Acid Monoethyl Ester;N2- (1-(S)-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine(for lisinopril);(S)-2-(((S)-1-Ethoxy-1-oxo-4-phenylbutan-2-yl)aMino)-6-(2,2,2-trifluoroacetaMido)hexanoic acid;N2-[(s)-ethoxycarbonyl-3-phenylpropy]-N8-trifluoroacetyl-L-lysine
• CAS NO: 116169-90-5
• Molecular Formula: C₂₀H₂₇F₃N₂O₅
• Molecular Weight: 432.43
• EINECS: 1806241-263-5
• Product Categories: Chemical intermediate for LISINOPRIL;Chemical Amines;Amines;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 116169-90-5.mol
• Article Data: 3

Chemical Properties

• Melting Point: 134-136°C
• Boiling Point: 586.987 °C at 760 mmHg
• Flash Point: 308.799 °C
• Appearance: White solid
• Density: 1.234 g/cm³
• Refractive Index: 1.495
• Storage Temp.: -20?C Freezer
• Solubility: DMSO, Methanol
• PKA: 2.25±0.24(Predicted)
• CAS DataBase Reference: N2-(1S-Ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine(CAS DataBase Reference)
• NIST Chemistry Reference: N2-(1S-Ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine(116169-90-5)
• EPA Substance Registry System: N2-(1S-Ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine(116169-90-5)

Safety Data

• Hazardous Substances Data: 116169-90-5(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

Different sources of media describe the Uses of 116169-90-5 differently. You can refer to the following data:
1. Lisinopryl intermediate
2. Lisinopryl intermediate.

InChI:InChI=1/C20H27F3N2O5/c1-2-30-18(28)15(14-8-4-3-5-9-14)11-13-24-16(17(26)27)10-6-7-12-25-19(29)20(21,22)23/h3-5,8-9,15-16,24H,2,6-7,10-13H2,1H3,(H,25,29)(H,26,27)/t15?,16-/m0/s1

Synthetic route

C8H12F3N2O3(1-)*C4H12N(1+) + ethyl (R)-2-hydroxy-4-phenylbutyrate (90315-82-5) → N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine (116169-90-5)

Conditions	Yield
Stage #1: ethyl (R)-2-hydroxy-4-phenylbutyrate With sodium carbonate; p-toluenesulfonyl chloride In dichloromethane at 0 - 25℃; for 8h; Stage #2: C8H12F3N2O3(1-)*C4H12N(1+) In dichloromethane at 15℃; for 10h;	86%

C8H12F3N2O3(1-)*Na(1+) + ethyl (R)-2-hydroxy-4-phenylbutyrate (90315-82-5) → N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine (116169-90-5)

Conditions	Yield
Stage #1: ethyl (R)-2-hydroxy-4-phenylbutyrate With pyridine; methanesulfonyl chloride In tetrahydrofuran at 0 - 35℃; for 6h; Stage #2: C8H12F3N2O3(1-)*Na(1+) In tetrahydrofuran at 25℃; for 10h;	84.7%

C8H12F3N2O3(1-)*Li(1+) + ethyl (R)-2-hydroxy-4-phenylbutyrate (90315-82-5) → N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine (116169-90-5)

Conditions	Yield
Stage #1: ethyl (R)-2-hydroxy-4-phenylbutyrate With methanesulfonyl chloride; triethylamine In tetrahydrofuran at 0 - 25℃; for 8h; Stage #2: C8H12F3N2O3(1-)*Li(1+) In tetrahydrofuran at 25℃; for 10h;	83%

di(benzothiazol-2-yl)disulfide (120-78-5) + N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine (116169-90-5) → (S)-2-[(S)-1-(Benzothiazol-2-ylsulfanylcarbonyl)-5-(2,2,2-trifluoro-acetylamino)-pentylamino]-4-phenyl-butyric acid ethyl ester (850705-63-4)

Conditions	Yield
Stage #1: di(benzothiazol-2-yl)disulfide With triphenylphosphine In dichloromethane for 0.75h; Stage #2: N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine at 25 - 30℃; for 2.5h;	45%

N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine (116169-90-5) → (S)-1-[(S)-2-((S)-1-Ethoxycarbonyl-3-phenyl-propylamino)-6-(2,2,2-trifluoro-acetylamino)-hexanoyl]-pyrrolidine-2-carboxylic acid ethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triphenylphosphine / CH2Cl2 / 0.75 h 1.2: 45 percent / 2.5 h / 25 - 30 °C 2.1: triethylamine / CH2Cl2 / 4 h / -15 - -10 °C View Scheme

bis(trichloromethyl) carbonate (32315-10-9) + N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine (116169-90-5) → C21H25F3N2O6

Conditions	Yield
In dichloromethane at 40℃; Inert atmosphere;

L-proline (147-85-3) + N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine (116169-90-5) → Nε-(trifluoroacetyl)-Nα-<(S)-1-(ethoxycarbonyl)-3-phenylpropyl>-L-lysyl-L-proline (103300-91-0)

Conditions	Yield
Stage #1: L-proline With tetrabutylammonium carbonate In ethanol at 50 - 60℃; for 0.166667h; Stage #2: N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine With 1-hydroxy-pyrrolidine-2,5-dione; dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 30℃; for 9h; Reagent/catalyst; Temperature;

Upstream product

• 90315-82-5 ethyl (R)-2-hydroxy-4-phenylbutyrate 

Downstream Products

• 103300-91-0 N^ε-(trifluoroacetyl)-N^α-<(S)-1-(ethoxycarbonyl)-3-phenylpropyl>-L-lysyl-L-proline 

Relevant articles and documents

Method for preparing lisinopril intermediate

The invention provides a method for preparing a lisinopril intermediate. The method comprises the following steps: treating (R)-2-hydroxy-4-phenylbutyrate in an organic solvent in the presence of alkali by using sulfonyl chloride so as to obtain a sulfonate solution; and reacting with trifluoroacetyllysine salt in the solution prepared in the previous step, separating after the reaction is ended, thereby obtaining N2-[1-(S)-alkoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine. The method for preparing the lisinopril intermediate, provided by the invention, is short in synthetic route, simple and convenient in operation, low in cost and suitable for industrialized production.

N2 -carboxy-3-phenylpropyl)-l-lysine derivative and process of producing lysinolpril using the compound

An N2 -(1-substituted-3-phenylpropyl)-L-lysine derivative is disclosed and is represented by formula (I) STR1 wherein R1 represents an acyl type or urethane type protective group; R2 represents a hydrogen atom, an alkyl group, or an aralkyl group. X represents a cyano (CN) group or an aminocarbonyl (CONH2) group; and the mark * represents the (S) position to the asymmetric carbon atom.