448964-37-2Relevant articles and documents
Preparation method of ramelteon
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Paragraph 0016-0022, (2020/06/16)
The invention belongs to the field of medicinal chemistry, and mainly relates to a (S)-2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)-1-ethylamine compound represented by a formula I. The method has the advantages that the operation is simple, the steps are reduced compared with the previous method, the route is shortened, and the used solvent is single in variety, convenient to recycle and high in yield, wherein the formula I is defined in the specification.
Preparation method of high-purity ramelteon
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, (2017/08/14)
The invention discloses a preparation method of high-purity ramelteon. The preparation method comprises the following steps: taking 1,2,6,7-tetrahydro-8H-indene[5,4-b]furan-8-ketone as a starting material; carrying out reduction and amino protection through wittig-horner reaction; carrying out amino deprotection under an acidic condition; carrying out hydrogenation reaction; then carrying out chiral resolution and acrylation reaction, thus obtaining the ramelteon. The ramelteon obtained through the invention is high in product purity and higher in yield; and formation of impurities is inhibited.
Preparation of 2 - (1, 6, 7, 8 - tetrahydro - 2H - indenyl and [5, 4 - b] furan - 8 - subunit of ethylamine
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Paragraph 0069; 0070; 0071, (2017/08/25)
The invention discloses a method for preparing 2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-idenethamine. The method comprises the following steps: (a) synthesizing a compound of a structural formula (III) by taking a compound of a structural formula (II) as an initial raw material under the conditions of certain temperature, catalyst, carbonic acid ditert-butyl ester, solvent and hydrogen source; (b) generating 2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-idenethamine from the compound of the structural formula (III) under the conditions of certain temperature, acid and solvent. In addition, the invention further discloses a novel compound, namely the compound of the structural formula (III). By adopting the method, the defects that the reaction of the conventional method is hard to control, the reaction time is too long and byproducts such as secondary amine and tertiary amine are easy to produce in the reaction process, are avoided.
A novel and practical synthesis of ramelteon
Xiao, Sa,Chen, Chao,Li, Hongyan,Lin, Kuaile,Zhou, Weicheng
, p. 373 - 377 (2015/03/30)
An efficient and practical process for the synthesis of ramelteon 1, a sedative-hypnotic, is described. Highlights in this synthesis are the usage of acetonitrile as nucleophilic reagent to add to 4,5-dibromo-1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-one 2 and the subsequent hydrogenation which successfully implement four processes (debromination, dehydration, olefin reduction, and cyano reduction) into one step to produce the ethylamine compound 13 where dibenzoyl-l-tartaric acid is selected both as an acid to form the salt in the end of hydrogenation and as the resolution agent. Then, target compound 1 is easily obtained from 13 via propionylation. The overall yield in this novel and concise process is almost twice as much as those in the known routes, calculated on compound 2.
PROCESS OF MAKING RAMELTEON AND RELATED SUBSTANCES
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Page/Page column 33, (2009/01/24)
The present patent application provides a process for the preparation of compounds of the Formula (I) Wherein represents a single bond or a double bond. R represents ethyl, vinyl or ethynyl.
Synthesis of a novel series of tricyclic indan derivatives as melatonin receptor agonists
Uchikawa, Osamu,Fukatsu, Kohji,Tokunoh, Ryosuke,Kawada, Mitsuru,Matsumoto, Kiyoharu,Imai, Yumi,Hinuma, Shuji,Kato, Koki,Nishikawa, Hisao,Hirai, Keisuke,Miyamoto, Masaomi,Ohkawa, Shigenori
, p. 4222 - 4239 (2007/10/03)
To develop a new therapeutic agent for sleep disorders, we synthesized a novel series of tricyclic indan derivatives and evaluated them for their binding affinity to melatonin receptors. In our previous paper, we proposed a conformation of the methoxy group favorable for the binding of the MT1 receptor. To fix the methoxy group in an active conformation, we decided to synthesize conformationally restricted tricyclic indan analogues with the oxygen atom in the 6-position incorporated into a furan, 1,3-dioxane, oxazole, pyran, morpholine, or 1,4-dioxane ring system. Among these compounds, indeno[5,4-b]furan analogues were found to be the most potent and selective MT1 receptor ligands and to have superior metabolic stability. The optimization of substituents led to (S)-(-)-22b, which showed very strong affinity for human MT1 (Ki = 0.014 nM), but no significant affinity for hamster MT3 (Ki = 2600 nM) or other neurotransmitter receptors. The pharmacological effects of (S)-(-)-22b were studied in experimental animals, and it was found that a dose of 0.1 mg/kg, po promoted a sleep in freely moving cats, as demonstrated by a decrease in wakefulness and increases in slow wave sleep and rapid eye movement sleep, which lasted for 6 h after administration. Melatonin (1 mg/kg, po) also had a sleep-promoting effect, though it lasted only 2 h. A new chiral method for the synthesis of (S)-(-)-22b starting from 60, which was prepared from 59 employing asymmetric hydrogenation with the (S)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl-Ru complex, was developed. (S)-(-)-22b (TAK-375) is currently under clinical trial for the treatment of insomnia and circadian rhythm disorders.
