96847-53-9

Usage

Uses

Given the provided materials, there are no specific applications listed for (1S,5R)-1-Phenyl-3-oxabicyclo[3.1.0]hexan-2-one. However, based on its structural features, it can be inferred that (1S,5R)-1-Phenyl-3-oxabicyclo[3.1.0]hexan-2-one may have potential uses in various industries such as pharmaceuticals, materials science, or as an intermediate in the synthesis of other organic compounds. To provide accurate applications, more context or information about its properties and reactivity would be required. If future data becomes available, the uses could be listed as follows:
Used in Pharmaceutical Industry:
(1S,5R)-1-Phenyl-3-oxabicyclo[3.1.0]hexan-2-one could be used as a pharmaceutical intermediate for the synthesis of drugs targeting specific biological pathways or receptors, given its complex structure and potential for molecular recognition.
Used in Materials Science:
(1S,5R)-1-Phenyl-3-oxabicyclo[3.1.0]hexan-2-one might be utilized as a component in the development of new materials with unique properties, such as polymers with specific mechanical or electronic characteristics, owing to its oxabicyclo and phenyl groups.
Used as a Research Chemical:
In academic or industrial research settings, (1S,5R)-1-Phenyl-3-oxabicyclo[3.1.0]hexan-2-one could serve as a starting material or a target molecule for studies aimed at understanding its reactivity, stability, or potential applications in various chemical processes.

Upstream product

• 51594-55-9 (R)-(-)-epichlorohydrin 
• 140-29-4 phenylacetonitrile 
• 60788-55-8 2-Hydroxymethyl-1-phenyl-cyclopropanecarbonitrile 
• 63106-93-4 1-phenyl-3-oxa-bicyclo[3.1.0]hexan-2-one 
• 67843-74-7 (S)-epichlorohydrin 
• 106-89-8 epichlorohydrin 
• 1797-74-6 allyl phenylacetate 
• 22613-99-6 cis-2-Hydroxymethyl-1-phenyl-cyclopropan-1-carbonsaeure 
• 96847-49-3 (1S,2R)-2-(hydroxymethyl)-1-phenyl-N-[(1R)-1-phenyl-ethyl]cyclopropanecarboxamide 
• 145193-16-4 allyl α-phenyl-α-diazoacetate 
• 103-80-0 phenylacetyl chloride 

Downstream Products

• 172015-99-5 (1 S,2 R)-N,N-diethyl-2-(hydroxymethyl)-1-phenylcyclopropane-carboxamide 
• 69160-63-0 (1S,2R)-2-(bromomethyl)-1-phenylcyclopropanecarboxylic acid 
• 459143-35-2 ((1S,2R)-2-Hydroxymethyl-1-phenyl-cyclopropyl)-pyrrolidin-1-yl-methanone 
• 459143-36-3 ((1S,2R)-2-Hydroxymethyl-1-phenyl-cyclopropyl)-piperidin-1-yl-methanone 
• 459143-33-0 (1S,2R)-1-phenyl-2-(hydroxymethyl)-N,N-di-isobutylcyclopropanecarboxamide 
• 69160-65-2 (1S,2R)-1-phenyl-2-(hydroxymethyl)-N-ethylcyclopropanecarboxamide 
• 459143-32-9 (1S,2R)-1-phenyl-2-(hydroxymethyl)-N,N-dibutylcyclopropanecarboxamide 
• 459143-30-7 (1S,2R)-1-phenyl-2-(hydroxymethyl)-N,N-dimethylcyclopropanecarboxamide 
• 459143-34-1 (1S,2R)-1-phenyl-2-(hydroxymethyl)-N,N-dibenzylcyclopropanecarboxamide 
• 1001017-62-4 (1S,2R)-2-(bromomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide 
• 96847-54-0 (1S,2R)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropane-1-carboxamide 
• 174848-98-7 (1S,2R)-2-(azidomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide 
• 936-98-1 ((R)-2-Phenyl-cyclopropyl)-methanol 
• 939-89-9 (1R)-1-carboxy-2-phenylcyclopropane 

Relevant academic research and scientific papers

IMPROVED PROCESS FOR THE PREPARATION OF LEVOMILNACIPRAN

The present invention discloses cost-effective, industrially efficient and safe process synthesis of levomilnacipran that is devoid of 1-phenyl-1- diethylaminocarbonyl-2- chloromethylcyclopropane.

Preparation method of levomilnacipran hydrochloride

The invention relates to the field of chemical medicines and organic synthesis and in particular relates to a preparation method of levomilnacipran hydrochloride. Aiming at solving the problems of anexisting method for preparing the levomilnacipran hydrochloride that the cost is relatively high or a generation process is relatively dangerous so that large-scale industrial production is limited, the preparation method is characterized by comprising the following steps: [1] enabling phenylacetonitrile and (R)-2-chloromethyl ethylene oxide to react under the action of sodium amide to obtain a compound 1; then carrying out hydrolysis cyclization on the compound 1 to obtain a compound 2; [2] enabling the compound 2 and thionyl chloride to react in alcohol, so as to obtain a compound 3; [3] enabling the compound 3 to be subjected to exchange reaction through introducing nitryl and amino, so as to obtain a compound 6; [4] reducing nitryl in the compound 6 and forming salt in situ to obtain the levomilnacipran hydrochloride. The preparation method provided by the invention is applicable to industrial production of the levomilnacipran hydrochloride.

(+)-Methyl (1 R, 2S)-2-{[4-(4-Chlorophenyl)-4-hydroxypiperidin-1-yl]methyl}-1-phenylcyclopropanecarboxylate [(+)-MR200] derivatives as potent and selective sigma receptor ligands: Stereochemistry and pharmacological properties

Methoxycarbonyl-1-phenyl-2-cyclopropylmethyl based derivatives cis-(+)-1a [cis-(+)-MR200], cis-(-)-1a [cis-(-)-MR201], and trans-(±)-1a [trans-(±)-MR204], have been identified as new potent sigma (σ) receptor ligands. In the present paper, novel enantiomerically pure analogues were synthesized and optimized for their σ receptor affinity and selectivity. Docking studies rationalized the results obtained in the radioligand binding assay. Absolute stereochemistry was unequivocally established by X-ray analysis of precursor trans-(+)-5a as camphorsulfonyl derivative 9. The most promising compound, trans-(+)-1d, showed remarkable selectivity over a panel of more than 15 receptors as well as good chemical and enzymatic stability in human plasma. An in vivo evaluation evidenced that trans-(+)-1d, in contrast to trans-(-)-1d, cis-(+)-1d, or cis-(-)-1d, which behave as σ1 antagonists, exhibited a σ1 agonist profile. These data clearly demonstrated that compound trans-(+)-1d, due to its σ1 agonist activity and favorable receptor selectivity and stability, provided an useful tool for the study of σ1 receptors.

PROCESS FOR THE PREPARATION OF (1S,2R)-MILNACIPRAN

The invention relates to a process for the preparation of Levomilnacipran, a compound useful in the treatment of depression, comprising the following steps: a) directly converting the enantiomerically enriched form of alcohol (D) into the enantiomerically enriched form of the phthalimido derivative (C) by treatment with phthalimide in the presence of a trialkyl or triarylphosphine and of a dialkyl azodicarboxylate, formula (I) wherein the amount of phthalimide is comprised between 1 and 1.3 equivalents with respect to the molar amount of alcohol (D) used, and the amounts of both the phosphine and the azodicarboxylate are comprised, independently from each other, between 1 and 1.5 equivalents with respect to the molar amount of alcohol (D) used; b) deblocking the enantiomerically enriched form of the phthalimido derivative (C) to obtain Levomilnacipran, formula (II).

COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEUROLOGICAL CONDITIONS

The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of neurological conditions may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of fibromyalgia, depression, neuropathic pain, severe pain, chronic pain, generalized pain, injury, post-operative pain, osteoarthritis, rheumatoid arthritis, multiple sclerosis, spinal cord injury, migraine, HIV related neuropathic pain, post herpetic neuralgia, diabetic neuropathy, cancer pain, fibromyalgia and lower back pain.

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

The orexin/hypocretin receptors are a family of G protein-coupled receptors and consist of orexin-1 (OX1) and orexin-2 (OX2) receptor subtypes. Orexin receptors are expressed throughout the central nervous system and are involved in the regulation of the sleep/wake cycle. Because modulation of these receptors constitutes a promising target for novel treatments of disorders associated with the control of sleep and wakefulness, such as insomnia, the development of orexin receptor antagonists has emerged as an important focus in drug discovery research. Here, we report the design, synthesis, characterization, and structure-activity relationships (SARs) of novel orexin receptor antagonists. Various modifications made to the core structure of a previously developed compound (-)-5, the lead molecule, resulted in compounds with improved chemical and pharmacological profiles. The investigation afforded a potential therapeutic agent, (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide (E2006), an orally active, potent orexin antagonist. The efficacy was demonstrated in mice in an in vivo study by using sleep parameter measurements. (Chemical Equation Presented).

AN IMPROVED PROCESS FOR THE PREPARATION OF 1-ARYL 2-AMINOMETHYL CYCLOPROPANE CARBOXYAMIDE (Z) DERIVATIVES, THEIR ISOMERS AND SALTS

The present invention relates to an improved and one-pot process for the preparation of 1-Aryl 2-aminomethyl cyclopropane carboxyamide (z) derivatives, their isomers of formula (I) or its pharmaceutically acceptable salt thereof wherein R1 and R2 are represents independently selected from the group consisting of hydrogen, lower alkyl, lower aryl, and lower-alkylaryl, which aryl or alkylaryl group is optionally substituted by a halogen atom.

PROCESS FOR PREPARING LEVOMILNACIPRAN HCL

The invention relates to one-pot process for preparing (1S,2R)-1-phenyl-1-(N,N-diethylaminocarbonyl)-2-aminomethylcyclopropane of formula (I) comprising the step of reacting (1S,2R)-N,N-diethyl-2-(hydroxymethyl)-1-phenylcyclopropanecarboxamide successively with the following reactants 1) triethyl orthoformate and methanesulfonic acid or triethylamine and methanesulfonyl chloride, 2) a phthalimidating agent, 3) aqueous EtNH2, wherein the reaction is carried out in toluene. In another aspect the invention concerns a process for preparing (1S,2R)-N,N-diethyl-2-(hydroxymethyl)-1-phenylcyclopropanecarboxamide trough a step of crystallization of (1S,5R)-1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one.

Enantioselective iron-catalyzed intramolecular cyclopropanation reactions

An iron-catalyzed asymmetric intramolecular cyclopropanation was realized in high yields and excellent enantioselectivity (up to 97% ee) by using the iron complexes of chiral spiro-bisoxazoline ligands as catalysts. The superiority of iron catalysts exhibited in this reaction demonstrated the potential abilities of this sustainable metal in asymmetric carbenoid transformation reactions.

Synthesis and evaluation of novel radioligands for positron emission tomography imaging of the orexin-2 receptor

Orexin receptors (OXRs) in the brain have been implicated in diverse physiological and neuropsychiatric conditions. Here we describe the design, synthesis, and evaluation of OXR ligands related to (1R,2S)-2-(((2-methyl-4- methoxymethylpyrimidin-5-yl)oxy)methyl)-N-(5-fluoropyridin-2-yl) -2-(3-fluorophenyl)cyclopropanecarboxamide (9a) applicable to positron emission tomography (PET) imaging. Structural features were incorporated to increase binding affinity for OXRs, to enable carbon-11 radiolabeling, and to adjust lipophilicity considered optimal for brain penetration and low nonspecific binding. 9a displayed nanomolar affinity for OXRs, and autoradiography using rat brain sections showed that specific binding of [11C]9a was distributed primarily to neocortical layer VI and hypothalamus, consistent with reported localizations of orexin-2 receptors (OX2Rs). In vivo PET study of [11C]9a demonstrated moderate uptake of radioactivity into rat and monkey brains under deficiency or blockade of P-glycoprotein, and distribution of PET signals in the brain was in agreement with autoradiographic data. Our approach and findings have provided significant information for development of OX2R PET tracers.