l-685,458

Base Information

• Chemical Name: l-685,458
• CAS No.: 292632-98-5
• Molecular Formula: C₃₉H₅₂N₄O₆
• Molecular Weight: 672.865
• Hs Code.: 29242990
• Nikkaji Number: J1.412.065C
• Wikidata: Q27145011
• Pharos Ligand ID: ADZNPX4N62UH
• ChEMBL ID: CHEMBL302004
• Mol file: 292632-98-5.mol

Synonyms:1-benzyl-4-(1-(1-carbamoyl-2-phenylethylcarbamoyl-3-methylbutylcarbamoyl)-2-hydroxy-5-phenylpentyl)carbamic acid tert-butyl ester;GSI-X cpd;L 685,458;L 685458;L-685,458;L-685458

Chemical Property of l-685,458

Chemical Property:

• Melting Point: 212-213 °C
• Boiling Point: 938.5±65.0 °C(Predicted)
• PKA: 12.09±0.46(Predicted)
• PSA: 159.85000
• Density: 1.155±0.06 g/cm3(Predicted)
• LogP: 6.34900
• Storage Temp.: −20°C
• Solubility.: DMSO: >10 mg/mL, soluble
• XLogP3: 5.9
• Hydrogen Bond Donor Count: 5
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 19
• Exact Mass: 672.38868539
• Heavy Atom Count: 49
• Complexity: 1030

Purity/Quality:

98%,99%, ^*data from raw suppliers

N-[(2R,4R,5S)-5-[[(1,1-Dimethylethoxy)carbonyl]amino]-4-hydroxy-1-oxo-6-phenyl-2-(phenylmethyl)hexyl]-L-leucyl-L-phenylalaninamide ^*data from reagent suppliers

Safty Information:

• Safety Statements: 22-24/25

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)CC(C(=O)NC(CC1=CC=CC=C1)C(=O)N)NC(=O)C(CC2=CC=CC=C2)CC(C(CC3=CC=CC=C3)NC(=O)OC(C)(C)C)O
• Isomeric SMILES: CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N)NC(=O)[C@H](CC2=CC=CC=C2)C[C@H]([C@H](CC3=CC=CC=C3)NC(=O)OC(C)(C)C)O
• Uses: N-[(2R,4R,5S)-5-[[(1,1-Dimethylethoxy)carbonyl]amino]-4-hydroxy-1-oxo-6-phenyl-2-(phenylmethyl)hexyl]-L-leucyl-L-phenylalaninamide, is a γ-Secretase Inhibitor, the enzyme complex that catalyzes the cleavage of the amyloid precursor protein (APP) to generate amyloid β-peptide (Aβ), the major causative agent in Alzheimer disease (AD). L-685,458 has been used to attenuate Notch signalling in ovary culture. It has also been used to analyze the specificity of the γ-secretase activity in brain tissue samples.

Technology Process of l-685,458

There total 61 articles about l-685,458 which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 94.0%

{(1S,2S,4R)-1-Benzyl-2-(tert-butyl-dimethyl-silanyloxy)-4-[(S)-1-((S)-1-carbamoyl-2-phenyl-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-5-phenyl-pentyl}-carbamic acid tert-butyl ester (126410-32-0) → {(1S)-benzyl-(4R)-[1-((1S)-carbamoyl-2-phenyl-ethylcarbamoyl)-(1S)-3-methyl-butyl-carbamoyl]-(2S)-hydroxy-5-phenyl-pentyl} carbamic acid tert-butyl ester (126409-24-3,292632-98-5)

Guidance literature:

With tetrabutyl ammonium fluoride; In tetrahydrofuran; at 20 ℃; for 48h;

DOI:10.1055/s-2003-37649

Reference yield: 64.0%

{(1S,2R,4R)-1-Benzyl-2-(tert-butyl-dimethyl-silanyloxy)-4-[(S)-1-((S)-1-carbamoyl-2-phenyl-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-5-phenyl-pentyl}-carbamic acid tert-butyl ester (338801-69-7) → (5S)-(tert-butoxycarbonylamino)-6-phenyl-(4R)-hydroxy-(2R)-benzylhexanoyl-L-leucy-L-phenylalaninamide (292632-98-5)

Guidance literature:

With tetrahydrofuran; tetrabutyl ammonium fluoride; at 20 ℃;

DOI:10.1016/S0040-4020(00)01167-4

Reference yield:

α-bromo-p-toluidine (63516-03-0) → {(1S)-benzyl-(4R)-[1-((1S)-carbamoyl-2-phenyl-ethylcarbamoyl)-(1S)-3-methyl-butyl-carbamoyl]-(2S)-hydroxy-5-phenyl-pentyl} carbamic acid tert-butyl ester (126409-24-3,292632-98-5)

Guidance literature:

Multi-step reaction with 7 steps

1: NaOEt / ethanol / 18 h / Ambient temperature

2: aq. LiOH / ethanol / 5 h

3: toluene / 24 h / Heating

4: aq. LiOH / 1,2-dimethoxy-ethane / 3 h / Ambient temperature

5: 1.) imidazole / 1.) DMF, RT, 24 h, 2.) DMF, MeOH, RT, 4 h

6: EDC*HCl, HOBt, Et₃N / dimethylformamide / 24 h / Ambient temperature

7: tetrabutylammonium fluoride / tetrahydrofuran / 24 h / Ambient temperature

With 1H-imidazole; lithium hydroxide; tetrabutyl ammonium fluoride; sodium ethanolate; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In tetrahydrofuran; 1,2-dimethoxyethane; ethanol; N,N-dimethyl-formamide; toluene;

DOI:10.1021/jm00088a004

upstream raw materials:

{(1S,2S,4R)-1-Benzyl-2-(tert-butyl-dimethyl-silanyloxy)-4-[(S)-1-((S)-1-carbamoyl-2-phenyl-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-5-phenyl-pentyl}-carbamic acid tert-butyl ester

(1S,4R)-{1-benzyl-4-[1-(1S)-carbamoyl-(2-phenylethylcarbamoyl)-(1S)-3-methylbutylcarbamoyl]-2-oxo-5-phenylpentyl}carbamic acid tert-butyl ester

N-tert-butoxycarbonyl-L-leucine

L-Phenylalanine amide

Downstream raw materials:

L-364,505

Refernces

• 1、 -. "Gamma secretase inhibitors". . . Retrieved 2008/06/13.
• 2、 Nadin, Alan,Sánchez López, José M,Neduvelil, Joseph G,Thomas, Steven R. "A stereocontrolled synthesis of 2R-benzyl-5S-tert-butoxycarbonylamino-4R-(tert-butyldimethylsilanyloxy)-6- phenyl-hexanoic acid (Phe-Phe hydroxyethylene dipeptide isostere)". . p. 1861 - 1864. Retrieved 2007/10/03.