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

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.

METHOD FOR PURIFYING N2-(1(S)-ETHOXYCARBONYL-3-PHENYLPROPYL)-N6-TRIFLUOROACETYL-L-LYSINE

A process for purifying N2-(1(S)-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine which comprises subjecting N2-(1(S)-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine contaminated with impurities to crystallization from a solvent comprising a water-soluble non-protic organic solvent, thereby removing the impurities into the mother liquor and giving crystals of N2-(1(S)-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine, according to which N2-(1(S)-ethoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysine having a high quality can be obtained in a high yield and a high productivity and which is suitable for practice on an industrial scale.

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.