- Synthesis and crystal structure of 1-(cyano(4-methoxyphenyl)methyl) cyclohexyl acetate
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The title compound, C17H21NO3, was synthesized by the acetylation of the hydroxy group of 1-(cyano(4-methoxyphenyl)methyl)cyclohexanol, which was formed by the reaction of 4-methoxyphenyl acetonitrile with cyclohexanone. The compound was characterized spectroscopically, and the structure was investigated by X-ray crystallography. The compound crystallizes in the orthorhombic crystal class in the space group Pbca with cell parameters a = 13.412(6) A, b = 12.398(14) A, c = 19.026(19) A and V = 3164(5) A3 for Z = 8. The cyclohexane ring is in a chair conformation. The structure exhibits intermolecular hydrogen bonds of the type C-H....N and C-H....O. Copyright Taylor & Francis Group, LLC.
- Mantelingu,Kavitha,Rangappa,Naveen,Sridhar,Prasad, J. Shashidhara
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Read Online
- Simple and an efficient method for the synthesis of 1-[2-dimethylamino-1- (4-methoxy-phenyl)-ethyl]-cyclohexanol hydrochloride: (±) venlafaxine racemic mixtures
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A novel synthetic method was developed for the synthesis of venlafaxine using inexpensive reagents. An improvement in the method, in the yield was achieved for the conversion of the venlafaxine. This is an improved version, simple and efficient method for the large-scale synthesis of venlafaxine.
- Basappa,Kavitha,Rangappa
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Read Online
- Method for industrially producing venlafaxine hydrochloride
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The invention discloses a method for industrially producing venlafaxine hydrochloride, and relates to the technical field of drug organic synthesis. The method has the advantages of easily available raw materials of the whole synthetic route, mild reaction conditions, simple and convenient operation, high yield, environment friendliness and good repeatability of the preparation method, and can be used for preparing venlafaxine hydrochloride with high yield and high purity.
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Paragraph 0028; 0062-0069
(2021/09/26)
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- Preparation method of venlafaxine amine impurity
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The invention discloses a preparation method of a venlafaxine amine impurity, and relates to the technical field of organic synthesis of medicines. P-methoxybenzyl cyanide and cyclohexanone are used as starting raw materials, condensation reaction is performed under the action of a phase transfer catalyst and alkali to obtain a compound 1, dehydration reaction is performed on the compound 1 under the action of acid to obtain a compound 2, and reduction reaction is conducted on the compound 2 under the action of a reducing agent to obtain an amine impurity I. The venlafaxine amine impurity (amine impurity I) with the structure is disclosed and successfully synthesized firstly, the purity of the venlafaxine amine impurity reaches 99% or above, and a high-purity impurity reference substance is provided for detection and content control of the impurity in venlafaxine hydrochloride medicine.
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Paragraph 0016; 0033-0035
(2021/05/12)
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- SUBSTITUTED ARYLUREA COMPOUNDS FOR INDUCING APOPTOSIS AND COMPOSITION FOR ANTICANCER COMPRISING THE SAME
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The present invention relates to a substituted arylurea compound inducing apoptosis and an anticancer composition comprising the same. The present invention relates to a novel compound capable of preventing, treating and alleviating cancer diseases such as prostate cancer, breast cancer, lung cancer, colorectal cancer, and skin cancer by inhibiting apoptosis of cancer cells and inhibiting proliferation of cancer cells.
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Paragraph 0119-0123
(2021/08/17)
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- Preparation method of venlafaxine impurity E (by machine translation)
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The invention belongs to the technical field of organic synthesis, and relates to a preparation method of venlafaxine impurity E, which comprises (1) a condensation reaction, (2) a reduction reaction and (3) a ring-forming reaction. The method for synthesizing venlafaxine impurity E is less in steps, high in product purity, safe in reaction, less in waste liquid, simple in post-treatment, convenient to operate and convenient for industrial production. (by machine translation)
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Paragraph 0025; 0029
(2020/09/30)
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- Method for preparing pharmaceutical intermediate with hydrotalcite material by catalysis
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The invention belongs to the technical field of medicine, and particularly relates to a method for preparing a pharmaceutical intermediate with a hydrotalcite material by catalysis. The method includes first utilizing lithium fluoride as a modifier to modify the Zn/Al hydrotalcite material to obtain a hydrotalcite-supported lithium fluoride material. The hydrotalcite-supported lithium fluoride material can catalyze 4-methoxybenzyl cyanide and cyclohexanone to have condensation reaction to prepare 1-hydroxycyclohexyl-4-methoxybenzyl cyanide. The defects in the prior art of harsh reaction conditions, low yield and high environment pollution in the preparation process of overcomes the harsh reaction conditions in the preparation of a PRISTIQ and/or venlafaxine framework are overcome.
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Paragraph 0052; 0054; 0058; 0060; 0062; 0063; 0064; 0065
(2018/11/22)
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- Selective Hydrogenation of Nitriles to Primary Amines Catalyzed by a Polysilane/SiO2-Supported Palladium Catalyst under Continuous-Flow Conditions
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Hydrogenation of nitriles to primary amines with heterogeneous catalysts under liquid-phase continuous-flow conditions is described. Newly developed polysilane/SiO2-supported Pd was found to be an effective catalyst and various nitriles were converted into primary amine salts in almost quantitative yields under mild reaction conditions. Interestingly, a complex mixture was obtained under batch conditions. Lifetime experiments showed that this catalyst remained active for more than 300 h (TON≥10 000) without loss of selectivity and no metal leaching from the catalyst occurred. By using this continuous-flow hydrogenation, synthesis of venlafaxine, an antidepressant drug, has been accomplished.
- Saito, Yuki,Ishitani, Haruro,Ueno, Masaharu,Kobayashi, Shū
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p. 211 - 215
(2017/04/21)
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- Screening of quinoline, 1,3-benzoxazine, and 1,3-oxazine-based small molecules against isolated methionyl-tRNA synthetase and A549 and HCT116 cancer cells including an in silico binding mode analysis
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Elevated activity of methionyl-tRNA synthetase (MRS) in many cancers renders it a possible drug target in this disease area, as well as in a series of parasitic diseases. In the present work, we report the synthesis and in vitro screening of a library of 1,3-oxazines, benzoxazines and quinoline scaffolds against human MRS. Among the compounds tested, 2-(2-butyl-4-chloro-1-(4-phenoxybenzyl)-1H-imidazol-5-yl)-5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecane (compound 21) and 2-(2-butyl-4-chloro-1-(4-nitrobenzyl)-1H-imidazol-5-yl)-2,4-dihydro-1H-benzo[d][1,3]oxazine (compound 8) were found to be potent inhibitors of MRS. Additionally, these compounds significantly suppressed the proliferation of A549 and HCT116 cells with IC50 values of 28.4, 17.7, 41.9, and 19.8 μM respectively. Molecular docking studies suggested that the ligand binding orientation overlaps with the original positions of both methionine and adenosine of MRS. This suggests the binding of compound 21 against MRS, which might lead the inhibitory activity towards cancer cells.
- Bharathkumar, Hanumantharayappa,Mohan, Chakrabhavi Dhananjaya,Rangappa, Shobith,Kang, Taehee,Keerthy,Fuchs, Julian E.,Kwon, Nam Hoon,Bender, Andreas,Kim, Sunghoon,Basappa,Rangappa, Kanchugarakoppal S.
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p. 9381 - 9387
(2015/09/15)
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- COMPOSITIONS AND METHODS FOR THE TREATMENT OF DEPRESSION
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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 treating or preventing depression may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of major depressive disorder (MDD), anxiety, neurological diseases, general anxiety disorder, social phobia, panic disorder, vasomotor symptoms, diabetic neuropathy, epilepsy, bipolar disorder, migraine, schizophrenia, cancer, menopause, HIV and familial adenomatous polyposis.
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Paragraph 0108; 0109
(2015/05/05)
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- DERIVATIVES OF (-)-VENLAFAXINE AND METHODS OF PREPARING AND USING THE SAME
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Methods of preparing, and compositions comprising, derivatives of (?)-venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders.
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Paragraph 0082
(2015/11/23)
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- COMPOSITIONS AND METHODS FOR THE TREATMENT OF DEPRESSION
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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 treating or preventing depression may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of major depressive disorder (MDD), anxiety, neurological diseases, general anxiety disorder, sodal phobia, panic disorder, vasomotor symptoms, diabetic neuropathy, epilepsy, bipolar disorder, migraine, schizophrenia, cancer, menopause, HIV and familial adenomatous polyposis.
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Paragraph 0094; 0095
(2013/12/03)
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- An improved and impurity-free large-scale synthesis of venlafaxine hydrochloride
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An improved and impurity-free synthetic method for large-scale synthesis of venlafaxine hydrochloride was developed using inexpensive reagents. The overall yield obtained from this newly developed process is 55% in a highly pure state with >99.9% purity by HPLC.
- Saravanan, Mohanarangam,Satyanarayana, Bollikonda,Reddy, Padi Pratap
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experimental part
p. 1392 - 1395
(2012/01/13)
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- A PROCESS FOR PREPARATION OF PHENETHYLAMINE DERIVATIVE
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The present invention relates to a process for the preparation of 1-[2-amino-1-(4-substituted phenyl)ethyl]cyclohexanol (3) (where R is OMe, OH), said process comprising the steps of; subjecting a reaction mixture of substituted phenylacetonitrile (2) in alcohol, an organic acid, and a hydrogenating catalyst in the presence of hydrogen gas pressure in the range of 0.5 kg/cm2 to 30 kg/cm2 and temperature in the range of 0-100°C; filtering and concentrating the cooled reaction mixture to obtain an acid addition salt of 1-[2-amino-1-(4-substituted phenyl)ethyl]cyclohexanol (4); and treating the acid addition salt of 1-[2-amino-1-(4-substituted phenyl)ethyl]cyclohexanol (4) with an ester in presence of a base to obtain 1-[2-amino-1-(4-substituted phenyl) ethyl] cyclohexanol (3).
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Page/Page column 10
(2010/09/18)
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- PROCESS FOR THE PREPARATION OF PHENETHYLAMINE DERIVATIVES
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The present invention relates to an improved process for the preparation of essentially pure Venlafaxine Hydrochloride. Particularly, the process for the preparation of Venlafaxine Hydrochloride comprises the following steps: i) Preparation of 1-[Cyano-1-(4-methoxyphenyl)methyl]cyclohexanol, ii) Preparation of crude Venlafaxine Hydrochloride by reduction of 1-[Cyano-1-(4-methoxyphenyl)methyl]cyclohexanol with Alkali metal borohydride and Lewis acid and subsequent conversion to Venalfaxine hydrochloride with formic acid and paraformaldehyde and finally iii) Purification of crude Venlafaxine Hydrochloride.
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Page/Page column 4
(2010/04/30)
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- A PROCESS FOR THE PREPARATION OF VENLAFAXINE HYDROCHLORIDE
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The present invention relates to a process for the preparation of Venlafaxine Hydrochloride comprising steps of i) treating 4-methoxyphenyl acetonitrile with cyclohexanone in presence of alkali hydroxide and super base to get 1-[cyano (4-methoxyphenyl) methyl] cyclohexanol and ii) reducing 1-[cyano (4-methoxyphenyl) methyl] cyclohexanol in presence of catalyst, activator and alcoholic ammonia under hydrogen pressure.
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Page/Page column 10-11
(2010/05/13)
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- IMPROVED PROCESS FOR THE PREPARATION OF PHENETHYLAMINE DERIVATIVES
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The present invention relates to an improved process for the preparation of essentially pure Venlafaxine Hydrochloride. Particularly, the process for the preparation of Venlafaxine Hydrochloride comprises the following steps: i) Preparation of l-[Cyano-l- (4-methoxyphenyl) methyl] cyclohexanol, ii) Preparation of crude Venlafaxine Hydrochloride by reduction of l-[Cyano-l-(4-methoxyphenyl) methyl] cyclohexanol with Alkali metal borohydride and Lewis acid and subsequent conversion to Venalfaxine hydrochloride with formic acid and paraformaldehyde and finally iii) Purification of crude Venlafaxine Hydrochloride.
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Page/Page column 6-7
(2008/12/07)
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- SOLID FORMS COMPRISING (-) O-DESMETHYLVENLAFAXINE AND USES THEREOF
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Solid forms comprising a compound useful in the treatment, prevention and management of various conditions and diseases are provided herein. In particular, the invention provides solid forms comprising (-)-O-desmethylvenlafaxine, including salts thereof, having utility for the treatment, prevention and management of conditions and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders.
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Page/Page column 61
(2008/12/08)
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- A NOVEL PROCESS FOR PREPARATION OF VENLAFAXINE HYDROCHLORIDE AND ITS INTERMEDIATES
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A process for the preparation of 1-cyano-[(4-methoxyphenyl)methyl] cyclohexanol by reacting cyclohexanone with the carbanion of 4-methoxyphenyl acetonitrile in the presence of polyethylene glycol-400 (PEG-400) or Aliquate-336, as a phase transfer catalyst (PTC). The present invention also relates to an novel process for the preparation of 1-[2-amino-1-(4-methoxyphenyl)ethyl]cyclohexanol, using borane-dimethyl sulphide complex (BDMS) or AlCl3-NaBH4, in refluxing tetrahydrofuran. 1-[2-Amino-1-(4-methoxyphenyl)ethyl]cyclohexanol thus obtained was subjected to N,N-dimethylation using formic acid-formaldehyde in boiling 1,4-dioxane: water mixture to obtain 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl] cyclohexanol in high purity, which was treated with isopropanol saturated with HCl gas to get venlafaxine hydrochloride in high purity and high yield.
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Page/Page column 7
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF HIGHLY PURE 1-[2-DIMETHYLAMINO-(4-METHOXYPHENYL) ETHYL]CYCLOHEXANOL HYDROCHLORIDE
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The invention encompasses processes for the preparation of highly pure venlafaxine hydrochloride, l-[2-dimethylamino-(4-methoxyphenyl)ethyl]cyclohexanol hydrochloride as well as intermediates thereof.
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Page/Page column 16; 17
(2010/11/27)
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- A PROCESS FOR THE PREPARATION OF VENLAFAXINE HYDROCHLORIDE
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A process for preparing venlafaxine hydrochloride and also a process for preparing l-[2-amino- l-(4-methoxy phenyl)ethyl]cyclohexanol hydrochloride, an intermediate of venlafaxine hydrochloride are disclosed. p-Methoxy phenyl acetonitrile is condensed with cyclohexanone in the presence of a base selected from alkali metal alkoxides and solvent selected from C4 alcohol at - 10 to - 5° C to obtain l-[cyano-l-(p-methoxy phenyl)m ethyl] cyclohexanol which is directly converted it into the l-[2-amino-l-(4-methoxy phenyl)ethyl] cyclohexanol without being isolated. The molar ratio of base to p-methoxy phenyl acetonitrile or cyclohexanone used is 0.1 to 0.4:1. The l-[2-amino-l-(4-methoxy phenyl)ethyl] cyclohexanol is converted its hydrochloride salt and subsequently formylated to venlafaxine base. The venlafaxine base is further converted into its salt namely venlafaxine hydrochloride. Both venlafaxine hydrochloride and l-[2-amino-l-(4-methoxy ρhenyl)ethyl] cyclohexanol hydrochloride are obtained in high yield with high purity.
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Page/Page column 11
(2008/06/13)
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- A PROCESS FOR THE MANUFACTURE OF VENLAFAXINE AND INTERMEDIATES THEREOF
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The present invention provides an improved process for the preparation of Venlafaxine and the intermediates thereof. The present invention provides a process for preparing compound of formula (IV), an intermediate for preparing Venlafaxine by hydrogenating a compound of formula (III): in the presence of toluene, water, and Raney nickel as catalyst with the process yield of 66% formula (IV) with 99% HPLC purity. The compound of formula (III) is prepared by drop wise addition of p-methoxyphenyl acetonitrile as a solution in tetrahydrofuran to the solution of butyl lithium in hexane the said process yields 89% of compound of formula (III) with 99.8% purity.
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Page/Page column 7; 11-12
(2010/10/20)
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- Method of preparing 1-[cyano(p-methoxyphenyl) ethyl]cyclohexanol
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The present invention is directed to a method of preparing 1-[cyano(p-methoxyphenyl)methyl]cyclohexanol. Particularly, the method of this invention includes reacting p-methoxyphenylacetonitrile with cyclohexanone in the presence of a solvent mixture including an aqueous solution of basic material and a water-soluble alcohol, to prepare 1-[cyano(p-methoxyphenyl)methyl]cyclohexanol represented by Formula 1 below. According to this method, 1-[cyano(p-methoxyphenyl)methyl]cyclohexanol, which is an important intermediate for use in the preparation of venlafaxine, exhibiting excellent efficacy as an antidepressant, may be very purely and economically prepared, and as well, may be industrially mass produced.
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Page/Page column 2
(2008/06/13)
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- Method of preparing 1-(cyano(p-methoxyphenyl)ethyl)cyclohexanol
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Disclosed herein is a method of preparing 1-[cyano(p-methoxyphenyl)ethyl]cyclohexanol. Particularly, the method of this invention includes reacting p-methoxyphenylacetonitrile with cyclohexanone in the presence of a solvent mixture including an aqueous solution of basic material and aqueous alcohol, to prepare 1-[cyano(p-methoxyphenyl)ethyl]cyclohexanol represented by Formula 1 below. According to this method, 1-[cyano(p-methoxyphenyl)ethyl]cyclohexanol, which is an important intermediate for use in the preparation of venlafaxine, exhibiting excellent efficacy as an antidepressant, may be very purely and economically prepared, and as well, may be industrially mass produced.
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Page/Page column 4
(2008/06/13)
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- Process for the preparation of phenethylamine derivatives
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The present invention relates to a process of preparing venlafaxine and derivatives thereof comprising reducing the corresponding β-hydroxynitriles using a reducing borohydride agent selected from tetraalkylammonium borohydride and aralkyltrialkylammonium borohydride. According to the present process, said β-hydroxynitrile can be prepared by condensating a phenylacetonitrile and cyclohexanone using a phase transfer catalyst and a base at a temperature of between 10-25 °C. Advantageously, in the present method, the use of hazardous catalysts and reducing agents is avoided and unexpectedly low amounts of reducing borohydride agent can be used.
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Page/Page column 5
(2008/06/13)
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- Synthesis and molecular structure analysis of venlafaxine intermediate and its analog
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1-(cyano-(4-methoxyphenyl) methyl cyclohexanol (2), C24U 32N2O2, a Venlafaxine intermediate is found to crystallize in both monoclinic (2a) and orthorhombic (2b) crystal systems. The form 2a crystallizes in the space group C2/c with the cell parameters a = 23.506(3), b = 5.550(3), c = 23.192(3), and β = 115.116(2)°. 2b crystallizes in space group P212121 with cell parameters α = 5.7850(6), b = 11.2680(6), and c = 20.6730(19). The intermolecular hydrogen bonding in the case of the monoclinic polymorph leads to the formation of dimer. The synthesis, characterization, and crystal structure studies of Venlafaxine analog 1-[2-1-(4-dimethylamino-phenyl)-ethylideneamino]- 1-(4-methoxyphenyl)-ethyl]-cyclohexanol (4) is reported. 4 crystallizes in P1 space group with cell parameters a = 10.801(7), b = 12.078(7), c = 9.928(5), α = 96.12(5)°, β = 110.49(5)°, and γ = 112.42(6)°.
- Kavitha,Lakshmi,Basappa,Mantelingu,Sridhar,Shashidhara Prasad,Rangappa
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p. 957 - 963
(2007/10/03)
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- Process for the preparation of 1-[cyano(phenyl)methyl]cyclohexanol compounds
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Process for the preparation of 1-[cyano(phenyl)methyl]cyclohexanol compounds of general formula (I): in which R1 is hydrogen or (C1-4)alkoxy, and R2 is hydrogen, (C1-4)alkyl or (C1-4)alkoxy, by reacting a compound of general formula (II): in which R1 and R2 are as defined above, with cyclohexanone in the presence of a catalyst, characterized in that this catalyst is selected from the group comprising alkali metal alcoholates, alkaline earth metal alcoholates, aluminium alcoholates and tetrasubstituted ammonium hydroxide.
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Page/Page column 2
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF 1-[CYANO(PHENYL)METHYL]-CYCLOHEXANOL COMPOUNDS
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Process for the preparation of 1-[cyano(phenyl)methyl]cyclohexanoI compounds of general formula (I): in which R1 is hydrogen or (C1-4)alkoxy, and R2 is hydrogen, (C1-4)alkyl or (C1-4)alkoxy, by reacting a compound of general formula (II): in which R1 and R2 are as defined above, with cyclohexanone in the presence of a catalyst, characterized in that this catalyst is selected from the group comprising alkali metal alcoholates, alkaline earth metal alcoholates, aluminium alcoholates and tetrasubstituted ammonium hydroxides.
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Page/Page column 4
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF ANTI-DEPRESSANT COMPOUND
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A process for the preparation of anti-depressant, compound of formula (I) or its pharmaceutically acceptable salts said process comprising reducing compound of formula (IIa) (wherein R is CONMe2) with sodium bis(2-methoxyethoxy) aluminium hydride followed by optional salt formation.
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Page/Page column 8
(2010/02/12)
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- Process for the preparation of cyclohexanol derivatives
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A reaction of a para-substituted aryl composition with cyclohexanone is facilitated by a metal hydride, such as NaH, KH, LiH, MgH2, CaH2, AlH3, and/or LiAlH4 to make first intermediates useful in producing a dru
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- Derivatives of venlafaxine and methods of preparing and using the same
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Methods of preparing, and compositions comprising, derivatives of venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders.
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- An efficient and green protocol for the preparation of cycloalkanols: A practical synthesis of venlafaxine
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The condensation of arylacetonitriles with cyclic ketones using aqueous NaOH or KOH under phase transfer catalysis gives almost quantitative yields of cycloalkanols. This protocol is utilized for a practical synthesis of the antidepression drug, venlafaxine 1.
- Chavan, Subhash P.,Khobragade, Dushant A.,Kamat, Subhash K.,Sivadasan, Latha,Balakrishnan, Kamalam,Ravindranathan,Gurjar, Mukund K.,Kalkote, Uttam R.
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p. 7291 - 7295
(2007/10/03)
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- A process for the preparation of 1-(cyano(aryl)methyl) cyclohexanol
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A process for the preparation of 1-[(cyano)aryl methyl]cyclohexanol of the general formula 1 (1a-d) by reacting cyclohexanone with the carbanions of an aryl acetonitrile of the general formula 3 (3a-d),a) R1 = H, R2 = Hb) R1 = OMe, R2 = Hc) R1 = OMe, R2 = OMed) R1 = OMe, R2 = cyclopentyloxy using a base, preferably Na OH or KOH, at a temperature in the range of 0-15xC for a time period in the range of 15 minutes to 120 minutes, isolating the compund of formula 1 and purifying the compund of formula 1a-d by crystallisation.
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- Preparation of cyclohexanol derivatives and novel thioamide intermediates
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The preparation of compounds having the formula I STR1 where R1 is --CN, --CO--N(CH3)2 or --CS--N(CH3)2 and R2 is hydrogen, methyl or a removable protecting group is carried out by condensing a compound having the formula STR2 where M is lithium, sodium, potassium or halomagnesium and R3 is methyl or a removable protecting group in a solvent comprising 80-100% of one or more hydrocarbons and 0-20% of one or more ethers. The solvent enables less inconvenient reaction temperatures to be used and higher yields to be obtained. Compounds (I) are new per se where R1 is --CS--N(CH3)2. Compounds (I) are chemical intermediates for preparing N,N-dimethyl-2-(1-hydroxycyclohexyl)-2-(4-hydroxyphenyl or 4-methoxyphenyl) ethylamine and pharmaceutically acceptable salts thereof. These end products are antidepressants.
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- 2-Phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives: Synthesis and antidepressant activity
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A series of 2-phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives was examined for the ability to inhibit both rat brain imipramine receptor binding and the synaptosomal uptake of norepinephrine (NE) and serotonin (5-HT). Neurotransmitter uptake inhibition was highest for a subset of 2-phenyl-2-(1-hydroxycyclohexyl)dimethylethylamines in which the aryl ring has a halogen or methoxy substituent at the 3- and/or 4-positions. Potential antidepressant activity in this subset was assayed in three rodent models - the antagonism of reserpine-induced hypothermia, the antagonism of histamine-induced ACTH release, and the ability to reduce noradrenergic responsiveness in the rat pineal gland. An acute effect seen in the rat pineal gland with several analogues, including 1-[1-(3,4-dichlorophenyl)-2-(dimethylamino)ethyl]cyclohexanol (23) and 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexanol (4), was taken as a possible correlate of a rapid onset of antidepressant activity. Compound 4 (venlafaxine) is presently undergoing clinical evaluation.
- Yardley,Morris Husbands,Stack,Butch,Bicksler,Moyer,Muth,Andree,Fletcher III,James,Sielecki
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p. 2899 - 2905
(2007/10/02)
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- 2-PHENYL-2-(1-HYDROXYCYCLOALKYL OR 1-HYDROXYCYCLOALK-2-ENYL)ETHYLAMINE DERIVATIVES
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This invention provides a group of hydroxycycloalkanephenethyl amine antidepressant derivatives of the following structural formula: STR1 in which A is a moiety of the formula STR2 where the dotted line represents optional unsaturation;R 1 is hydrogen or alkyl;R 2 is alkyl;R. sub.4 is hydrogen, alkyl, formyl or alkanoyl;R 5 and R 6 are, independently, hydrogen, hydroxyl, alkyl, alkoxy, alkanoyloxy, cyano, nitro, alkylmercapto, amino, alkylamino, dialkylamino, alkanamido, halo, trifluoromethyl or, taken together, methylenedioxy;R. sub.7 is hydrogen or alkyl; andn is 0, 1, 2, 3 or 4;or a pharmaceutically acceptable salt thereof.
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