- Preparation method of ramelteon impurity
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The invention relates to a preparation method of a ramelteon impurity, and belongs to the technical field of chemical synthesis. The preparation method comprises the following steps: (1) reacting a compound I with oxalyl chloride to generate an acyl chloride compound, adding aluminum trichloride, and carrying out a Friedel-Crafts reaction to generate a compound II; and (2) directionally generatinga compound III from the compound II under the action of Raney cobalt and hydrazine hydrate. The preparation method provides a novel and safe reduction condition for direct synthesis of the monosubstituted impurity, and the product does can be directly used as an impurity reference substance without purification, and also can be directly subjected to a subsequent impurity transfer experiment.
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Paragraph 0029-0031; 0043-0045
(2020/02/29)
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- Pharmaceutical preparation containing copolyvidone
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A stabilized preparation which comprises: a unstable drug in a polyethylene glycol-containing preparation; and a coating agent comprising a copolyvidone instead of polyethylene glycol with which the drug is coated.
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- PROCESS FOR PREPARATION OF (S)-N-[2-(1,6,7,8-TETRAHYDRO-2H-INDENO[5,4-B]FURAN-8-YL)ETHYL] PROPIONAMIDE AND NOVEL INTERMEDIATES THEREOF
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Disclosed herein process for preparation of (S)-Ramelteon and intermediates thereof.
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Page/Page column 30
(2010/04/28)
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- PROCESS OF MAKING RAMELTEON AND RELATED SUBSTANCES
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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.
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- PROCESS FOR THE SYNTHESIS OF RAMELTEON AND ITS INTERMEDIATES
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The present invention provides processes and intermediates for the synthesis of ramelteon.
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- PROCESS FOR PRODUCTION OF OPTICALLY ACTIVE AMINE DERIVATIVES
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An industrial process for production of high-purity optically active amine derivatives in high yield while inhibiting the formation of by-products, which comprises subjecting (E)-2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-ylidene)ethylamine to asymmetric reduction, catalytically reducing the obtained product at a reaction temperature of 40 to 100°C and a pH of 3 to 9, subjecting the obtained (S)-2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethylamine to propionylation, and then crystallizing the reaction mixture.
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Page/Page column 12
(2008/06/13)
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- Pharmaceutical preparation containing copolyvidone
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A stabilized preparation which comprises: a unstable drug in a polyethylene glycol-containing preparation; and a coating agent comprising a copolyvidone instead of polyethylene glycol with which the drug is coated.
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- PHARMACEUTICAL PREPARATION CONTAINING COPOLYVIDONE
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A stabilized preparation which comprises: a unstable drug in a polyethylene glycol-containing preparation; and a coating agent comprising a copolyvidone instead of polyethylene glycol with which the drug is coated.
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- Synthesis of a novel series of tricyclic indan derivatives as melatonin receptor agonists
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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.
- Uchikawa, Osamu,Fukatsu, Kohji,Tokunoh, Ryosuke,Kawada, Mitsuru,Matsumoto, Kiyoharu,Imai, Yumi,Hinuma, Shuji,Kato, Koki,Nishikawa, Hisao,Hirai, Keisuke,Miyamoto, Masaomi,Ohkawa, Shigenori
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p. 4222 - 4239
(2007/10/03)
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- Bicyclic compounds and pharmaceutical composition containing tricyclic compound for treating or preventing sleep disorders
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A compound having the following general fomula: wherein R1 is an optionally substituted hydrocarbon, amino or heterocyclic group; R2 is H or an optionally substituted hydrocarbon group; R3 is H or an optionally substituted hydrocarbon or heterocyclic group; X is CHR4, NR4, O or S in which R4 is H or an optionally substituted hydrocarbon group; R5 is H, a halogen atom, C1-6 alkyl group, a C1-6 alkoxy group, a hydroxy group, a nitro group, a cyano group or an amino group wherein the C1-6 alkyl group, the C1-6 alkoxy group and the amino group may be substituted by 1 to 5 substituents, Y is C or N; ring B is an optionally substituted benzene ring; m = 1 to 4 and n = 0 to 2; L represents a leaving group such as a halogen atom, an alkylsulfonyl group, an alkylsulfonlyoxy group and arylsulfonyloxy group; or a salt thereof.
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Referential example 17
(2010/11/29)
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- Method for treating or preventing sleep disorders
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The present invention provides a pharmaceutical composition for treating or preventing sleep disorders which comprises (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethyl]propionamide in combination with at least one active component selected from zolpidem, zopiclone, triazolam and brotizolam.
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- Tricyclic compounds, their production and use
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A compound of the formula: STR1 wherein R1 is an optionally substituted hydrocarbon, amino or heterocyclic group; R2 is H or an optionally substituted hydrocarbon group; R3 is H or an optionally substituted hydrocarbon or heterocyclic group; X is CHR4, NR4, O or S in which R4 is H or an optionally substituted hydrocarbon group; Y is C, CH or N; ring A is optionally substituted 5- to 7-membered ring; ring B is an optionally substituted benzene ring; and m is 1 to 4, or a salt thereof, a process for producing it, an intermediate for the production and a pharmaceutical composition comprising it are provided.
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