Lemborexant

Base Information

• Chemical Name: Lemborexant
• CAS No.: 1369764-02-2
• Molecular Formula: C22H20F2N4O2
• Molecular Weight: 410.423
• Mol file: 1369764-02-2.mol

Synonyms:Lemborexant;lemborexant,E2006;(1R,2S)-2-[[(2,4-Dimethyl-5-pyrimidinyl)oxy]methyl]-2-(3-fluorophenyl)-N-(5-fluoro-2-pyridinyl)cyclopropanecarboxamide;E 2006

Chemical Property of Lemborexant

Chemical Property:

• Boiling Point: 596.1±50.0 °C(Predicted)
• PKA: 12.30±0.40(Predicted)
• PSA: 77.00000
• Density: 1.347±0.06 g/cm3(Predicted)
• LogP: 3.81500
• Storage Temp.: -20°C, Inert atmosphere
• Solubility.: DMSO (Slightly), Methanol (Slightly)

Purity/Quality:

99%, ^*data from raw suppliers

Lemborexant(E2006) >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Lemborexant is a newer orexin receptor antagonist which is submitted to US FDA for review as new drug application for the treatment of insomnia after completing two key Phase 3 studies of lemborexant – SUNRISE 1 (Study 304) and SUNRISE 2 (Study 303).
• Uses: Lemborexant is a novel orexin receptor antagonist and is used in the treatment of insomnia, characterised by difficulties with sleep onset or sleep maintenance. Orexins are neuropeptides involved in regulating sleep and arousal by promoting wakefulness. Lemborexant blocks the binding of orexins A and B to their receptors 1 and 2 thereby reducing wakefulness and promoting sleep. Suvorexant is the other orexin receptor antagonist marketed in Australia for insomnia.
• Drug interactions: Lemborexant is metabolized by CYP3A4 and is susceptible to interactions with medications such as amiodarone, amlodipine, carbamazepine, clarithromycin, diltiazem, fluoxetine and phenytoin. Lemborexant may affect other medications metabolised by CYP2B6, such as bupropion and methadone. Alcohol should be avoided: a single dose of alcohol can increase lemborexant concentrations up to 70%.

Technology Process of Lemborexant

There total 20 articles about Lemborexant 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: 56.4%

(1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)cyclopropanecarboxylic acid (1369769-35-6) + 2-amino-5-fluoropyridine (21717-96-4) → (1R,2S)-2-[{(2,4-dimethylpyrimidin-5-yl)oxy}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide (1369764-02-2)

Guidance literature:

With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20 - 60 ℃;

DOI:10.1021/acs.jmedchem.5b00217

Reference yield:

C17H16ClFN2O2 (1369769-31-2) + 2-amino-5-fluoropyridine (21717-96-4) → (1R,2S)-2-[{(2,4-dimethylpyrimidin-5-yl)oxy}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide (1369764-02-2)

Guidance literature:

With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 10 - 60 ℃; for 2h;

Reference yield:

C16H14F2N2O2 + 5-hydroxy-2,4-dimethylpyrimidine (412003-95-3) → (1R,2S)-2-[{(2,4-dimethylpyrimidin-5-yl)oxy}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide (1369764-02-2)

Guidance literature:

With di-tert-butyl-diazodicarboxylate; triphenylphosphine; In tetrahydrofuran; toluene; at 20 ℃; for 4h; Temperature;

upstream raw materials:

C₁₇H₁₆ClFN₂O₂

2-amino-5-fluoropyridine

(1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)cyclopropanecarboxylic acid

(1S,2R)-1-(3-fluorophenyl)-2-(hydroxymethyl)cyclopropane-1-carboxylic acid

Downstream raw materials:

(1R,2S)-2-(((2-methyl-4-bromomethylpyrimidin-5-yl)oxy)methyl)-N-(5-fluoropyridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide

(1R,2S)-2-(((2-methyl-4-hydroxymethylpyrimidin-5-yl)oxy)-methyl)-N-(5-fluoropyridin-2-yl)-2-(3-fluorophenyl)-cyclopropanecarboxamide

(1R,2S)-2-{[(4-fluoromethyl-2-methylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide

Refernces

• 1、 Yoshida, Yu,Naoe, Yoshimitsu,Terauchi, Taro,Ozaki, Fumihiro,Doko, Takashi,Takemura, Ayumi,Tanaka, Toshiaki,Sorimachi, Keiichi,Beuckmann, Carsten T.,Suzuki, Michiyuki,Ueno, Takashi,Ozaki, Shunsuke,Yonaga, Masahiro. "Discovery of (1R,2S)-2-{[(2,4-Dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide (E2006): A Potent and Efficacious Oral Orexin Receptor Antagonist". . p. 4648 - 4664. Retrieved 2015/06/30.
• 2、 -. "METHODS AND COMPOUNDS USEFUL IN THE SYNTHESIS OF OREXIN-2 RECEPTOR ANTAGONISTS". . . Retrieved 2013/08/28.