ChemicalBook > CAS DataBase List > Ramelteon

Ramelteon

Product Name
Ramelteon
CAS No.
196597-26-9
Chemical Name
Ramelteon
Synonyms
Rozerem;N-[2-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]propanamide;(S)-N-(2-(2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8-yl)ethyl)propionamide;DF883;CS-1962;TAK-375;RAMELTEON;Rhodialux;rac Rozerem;Rametylamine
CBNumber
CB0496858
Molecular Formula
C16H21NO2
Formula Weight
259.34
MOL File
196597-26-9.mol
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Ramelteon Property

Melting point:
113-1150C
alpha 
D20 -57.8° (c = 1.004 in chloroform)
Boiling point:
455.3±24.0 °C(Predicted)
Density 
1.119±0.06 g/cm3(Predicted)
Flash point:
2℃
storage temp. 
Sealed in dry,Store in freezer, under -20°C
solubility 
Dimethyl Sulfoxide, Ethanol, Methanol,
form 
Solid
pka
16.37±0.46(Predicted)
color 
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 DataBase Reference
196597-26-9(CAS DataBase Reference)
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Safety

Hazard Codes 
F,Xn
Risk Statements 
11-20/21/22-36
Safety Statements 
16-36/37
RIDADR 
UN 1648 3 / PGII
WGK Germany 
2
HS Code 
2932.99.7000
Hazardous Substances Data
196597-26-9(Hazardous Substances Data)
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H302Harmful if swallowed

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N-Bromosuccinimide Price

Sigma-Aldrich
Product number
SML2262
Product name
Ramelteon
Packaging
10MG
Price
$128
Updated
2024/03/01
Sigma-Aldrich
Product number
SML2262
Product name
Ramelteon
Packaging
50MG
Price
$514
Updated
2024/03/01
Sigma-Aldrich
Product number
R-016
Product name
Ramelteon solution
Purity
1.0?mg/mL in acetonitrile, ampule of 1?mL, certified reference material, Cerilliant?
Packaging
1mL
Price
$205
Updated
2022/05/15
TCI Chemical
Product number
R0216
Product name
Ramelteon
Packaging
100MG
Price
$155
Updated
2024/03/01
TCI Chemical
Product number
R0216
Product name
Ramelteon
Packaging
1G
Price
$620
Updated
2024/03/01
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Ramelteon Chemical Properties,Usage,Production

Description

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.

Chemical Properties

Crystalline Solid

Originator

Takeda (Japan)

Uses

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.

Definition

ChEBI: N-[2-[(8S)-2,6,7,8-tetrahydro-1H-cyclopenta[e]benzofuran-8-yl]ethyl]propanamide is a member of indanes.

brand name

Rozerem (Takeda).

General Description

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.

Synthesis

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.

Drug interactions

Since CYP1A2 is the major isozyme involved in the hepatic metabolism of ramelteon, it should not be taken in combination with strong CYP1A2 inhibitors, such as fluvoxamine. Co-administration with either ketoconazole (a CYP3A4 inhibitor) or fluconazole (a potent CYP2C9 inhibitor) resulted in significant increases in AUC and Cmax, but the extensive metabolism and highly variable plasma concentrations of ramelteon precluded the need for dose modification. The package insert, however, cautions patients about co-administration with potent CYP3A4 and CYP2C9 inhibitors.

storage

Store at -20°C

References

[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 Preparation Products And Raw materials

Raw materials

Preparation Products

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Ramelteon Suppliers

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View Lastest Price from Ramelteon manufacturers

Hong Kong Excellence Biotechnology Co., Ltd.
Product
Ramelteon 196597-26-9
Price
US $100.00/kg
Min. Order
1kg
Purity
99.9%
Supply Ability
20tons
Release date
2023-10-12
Henan Bao Enluo International TradeCo.，LTD
Product
Ramelteon 196597-26-9
Price
US $100.00/kg
Min. Order
1kg
Purity
99%
Supply Ability
500t/month
Release date
2023-07-21
Hebei Zhanyao Biotechnology Co. Ltd
Product
Ramelteon 196597-26-9
Price
US $10.00/Kg/Bag
Min. Order
1Kg/Bag
Purity
99%
Supply Ability
20 Tons
Release date
2021-11-02

196597-26-9, RamelteonRelated Search:

Polyacrylamide Ethylparaben Ethyl formate Ethyl cyanoacetate Acrylamide Furan ISOXADIFEN-ETHYL Ethyl acetate Polyamide Ethanol Tetrahydrofuran Ethyl pyruvate N,N-Dimethylformamide Nicotinamide Temozolomide Ethyl acrylate 1,2,6,7-Tetrahydro-8H-indeno[5,4-b]furan-8-one Boc-D-Glutamine

  • CS-1962
  • TAK-375; ROZEREM; TAK375; TAK 375;
  • N-[2-[(8S)-1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]propanamide
  • N-[2-[(8S)-2,6,7,8-tetrahydro-1H-cyclopenta[e][1]benzofuran-8-yl]ethyl]propanamide
  • UNII-901AS54I69
  • 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)
  • Rozerem
  • 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
  • (S)-N-(2-(2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8-yl)ethyl)propionamide
  • 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%
  • 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
  • Ray for amine
  • Rametylamine
  • 196597-26-9
  • ROZEREM
  • Other APIs
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • Chiral Reagents