Ramelteon

Ramelteon Struktur
196597-26-9
CAS-Nr.
196597-26-9
Englisch Name:
Ramelteon
Synonyma:
Rozerem;(S)-N-(2-(2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8-yl)ethyl)propionamide;N-[2-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]propanamide;DF883;TAK-375;CS-1962;RAMELTEON;Rhodialux;rac Rozerem;Rametylamine
CBNumber:
CB0496858
Summenformel:
C16H21NO2
Molgewicht:
259.34
MOL-Datei:
196597-26-9.mol

Ramelteon Eigenschaften

Schmelzpunkt:
113-1150C
alpha 
D20 -57.8° (c = 1.004 in chloroform)
Siedepunkt:
455.3±24.0 °C(Predicted)
Dichte
1.119±0.06 g/cm3(Predicted)
Flammpunkt:
2℃
storage temp. 
Sealed in dry,Store in freezer, under -20°C
Löslichkeit
Dimethyl Sulfoxide, Ethanol, Methanol,
Aggregatzustand
Solid
pka
16.37±0.46(Predicted)
Farbe
Crystalline
InChI
InChI=1S/C16H21NO2/c1-2-15(18)17-9-7-12-4-3-11-5-6-14-13(16(11)12)8-10-19-14/h5-6,12H,2-4,7-10H2,1H3,(H,17,18)/t12-/m0/s1
InChIKey
YLXDSYKOBKBWJQ-LBPRGKRZSA-N
SMILES
C(NCC[C@H]1C2=C3CCOC3=CC=C2CC1)(=O)CC
CAS Datenbank
196597-26-9(CAS DataBase Reference)
Sicherheit
  • Risiko- und Sicherheitserklärung
  • Gefahreninformationscode (GHS)
Kennzeichnung gefährlicher F,Xn
R-Sätze: 11-20/21/22-36
S-Sätze: 16-36/37
RIDADR  UN 1648 3 / PGII
WGK Germany  2
HS Code  2932.99.7000
Giftige Stoffe Daten 196597-26-9(Hazardous Substances Data)
Bildanzeige (GHS) GHS hazard pictograms
Alarmwort Warnung
Gefahrenhinweise
Code Gefahrenhinweise Gefahrenklasse Abteilung Alarmwort Symbol P-Code
H302 Gesundheitsschädlich bei Verschlucken. Akute Toxizität oral Kategorie 4 Warnung GHS hazard pictogramssrc="/GHS07.jpg" width="20" height="20" /> P264, P270, P301+P312, P330, P501
Sicherheit

Ramelteon Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung

Ramelteon, also known as N-[2-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]propanamide, is a melatonin agonist developed by Takeda Pharmaceuticals, Inc. It was approved by the FDA for marketing in the United States in September 2005 and is marketed under the name Rozerem. It is used to treat difficult-to-sleep and short-term insomnia. Ramelteon is effective for both chronic and short-term insomnia. Unlike most treatments of insomnia that target the GABA (g-aminobutyric acid) receptor complex, ramelteon is an agonist of the melatonin receptor. In particular, it has high selectivity for the MT1 and MT2 subtypes, which have been implicated in the maintenance of circadian rhythms, over the MT3 receptor responsible for other melatonin functions. Its lack of affinity for not only the GABA receptor complex but also neurotransmitter, dopaminerigic, opiate, and benzodiazepine receptors suggests an improved safety profile devoid of the abuse potential of the hypnotic drugs that target these receptors. As such, ramelteon is not a scheduled drug.

Chemische Eigenschaften

Crystalline Solid

Verwenden

Ramelteon is a selective melatonin receptor agonist of MT1 and MT2 approved for the treatment of insomnia (trouble in sleeping). It acts as a sedative and hypnotic agent. Ramelteon is the only prescription sleep aid not designated as a Schedule IV controlled substance.

Allgemeine Beschreibung

The melatonin molecule was modified mainly by replacing the nitrogen of the indole ring with a carbon to give an indane ring and by incorporating 5-methoxyl group in the indole ring into a more rigid furan ring. The selectivity of the resulting ramelteon for MT1 receptor is eight times more than that of MT2 receptor. Unlike melatonin, it is more effective in initiating sleep (MT1 activity) rather than to readjust the circadian rhythm (MT2 activity). It appears to be distinctly more efficacious than melatonin but less efficacious than benzodiazepines as a hypnotic. Importantly, this drug has no addiction liability (it is not a controlled substance). As a result, it has recently been approved for the treatment of insomnia.

Synthese

Vilsmeier-Haack reaction on benzofuran 112 provided aldehyde 113 (100%), which was converted to olefin 114 (88%) by Horner-Emmons reaction with triethylphosphonoacetate, and was followed by hydrogenation of the olefin to give ester 115 (100%). In order to avoid the cyclization of the acid chloride intermediate into the wrong position, the benzene ring was protected by bromination. Both bromination and hydrolysis of the ester is accomplished in a single pot to give acid 116. Thus the ester is brominated with bromine in sodium acetate and acetic acid at 0°C and RT for several hours followed by quenching of remaining bromide by sodium thiosulfate. The resulting acidic solution was taken up in acetonitrile and refluxed for 2hr to provide the acid 116 in 73% yield. The conversion of the acid to acid chloride was done by reacting with thionyl chloride in odichlorobenzene at 40°C for 30 to 40 min after which the reaction was cooled to 0°C . Aluminum trichloride was added and the reaction mixture was stirred at 0°C for 30 min to deliver cyclized ketone 117 in 92% yield. After completion of the cyclization, the bromines are removed by hydrogenation (86%) and resulting ketone 118 was then reacted under Horner-Emmons condition with diethyl cyano phosphonate to give vinyl nitrile 119 in 84% yield. Selective reduction of the nitrile was accomplished by hydrogenation under basic condition (sodium hydroxide in toluene) in the presence of the activated cobalt at 25-50°C for 6.5 hr. The amine was recovered as hydrochloride salt 120 (99% yield) by treating the amine with HCl in methanol. In the next step, the amine salt 120 was taken up in toluene and treated with sodium hydroxide followed by hydrogenation of the mixture with [RuCl(benzene)(R)-BINAP]Cl as catalyst to provide chiral amine 121, after several work up and palladium catalyzed hydrogenations, in 73% overall yield. Final acylation of the amine with propionyl chloride in the presence of aqueous sodium hydroxide in THF at room temperature gave the desired product ramelteon (XVI), after crystallization, in 97% yield.
Synthesis of Ramelteon (196597-26-9)

Einzelnachweise

[1] KATOKOKI. Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist.[J]. Neuropharmacology, 2005. DOI:10.1016/j.neuropharm.2004.09.007.
[2] MIYAMOTO M. Pharmacology of Ramelteon, a Selective MT1/MT2 Receptor Agonist: A Novel Therapeutic Drug for Sleep Disorders[J]. CNS Neuroscience & Therapeutics, 2009. DOI:10.1111/j.1755-5949.2008.00066.x.
[3] MCGECHANADAM  WellingtonKeri. Ramelteon.[J]. CNS drugs, 2005. DOI:10.2165/00023210-200519120-00007.
[4] BORJANANCY L   DanielKaren L. Ramelteon for the treatment of insomnia.[J]. Clinical therapeutics, 2006. DOI:10.1016/j.clinthera.2006.10.016.

Ramelteon Upstream-Materialien And Downstream Produkte

Upstream-Materialien

Downstream Produkte


Ramelteon Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global( 386)Lieferanten
Firmenname Telefon E-Mail Land Produktkatalog Edge Rate
Hong Kong Excellence Biotechnology Co., Ltd.
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ada@sh-teruiop.com China 893 58
Henan Bao Enluo International TradeCo.,LTD
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Shanghai Aosiris new Material Technology Co., LTD
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Capot Chemical Co.,Ltd.
571-85586718 +8613336195806
sales@capotchem.com China 29797 60
Beijing Cooperate Pharmaceutical Co.,Ltd
010-60279497
sales01@cooperate-pharm.com CHINA 1811 55
Henan Tianfu Chemical Co.,Ltd.
+86-0371-55170693 +86-19937530512
info@tianfuchem.com China 21691 55
Shanghai Time Chemicals CO., Ltd.
+86-021-57951555 +8617317452075
jack.li@time-chemicals.com China 1807 55
ATK CHEMICAL COMPANY LIMITED
+undefined-21-51877795
ivan@atkchemical.com China 32480 60
career henan chemical co
+86-0371-86658258
sales@coreychem.com China 29914 58

196597-26-9()Verwandte Suche:


  • rac N-[-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]propanamide
  • rac Ramelteon
  • rac Rozerem
  • TAK-375
  • RAMELTEON(FORR&DONLY)
  • (S)-N-[2-(1,6,7,8-Tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide
  • N-[-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-β]furan-8-yl]ethyl]propanamide
  • Ramelteon (approx. 90% S)
  • RAMELTEON
  • rac N-[-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-β]furan-8-yl]ethyl]propanamide
  • N-[-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]propanamide
  • rac Ramelteon DISCONTINUED. See R110051
  • RaMelteon(TAK-375)
  • N-(2-(2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8-yl)ethyl)propionaMide
  • RaMelteon,(S)-N-[2-(1,6,7,8-Tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionaMide
  • Ramelteon solution
  • Ramelteon, >=99%
  • CS-1962
  • TAK-375; ROZEREM; TAK375; TAK 375;
  • N-[2-[(8S)-2,6,7,8-tetrahydro-1H-cyclopenta[e][1]benzofuran-8-yl]ethyl]propanamide
  • UNII-901AS54I69
  • Propanamide, N-[2-[(8S)-1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]-
  • Ramelteon USP/EP/BP
  • DF883
  • RamelteonQ: What is Ramelteon Q: What is the CAS Number of Ramelteon Q: What is the storage condition of Ramelteon Q: What are the applications of Ramelteon
  • P Sanduvor 3035
  • Rhodialux
  • Rozerem
  • (S)-N-(2-(2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8-yl)ethyl)propionamide
  • N-[2-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]propanamide
  • Ray for amine
  • Rametylamine
  • 196597-26-9
  • ROZEREM
  • Other APIs
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • Chiral Reagents
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