- Preparation method of raloxifene hydrochloride and intermediate thereof
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The preparation method comprises the following steps: preparing a raloxifene hydrochloride precursor (intermediate 2) from 1-{4-[2-(piperidine-1-yl)ethyoxyl]phenyl}-2-(2-sulfydryl-4-methoxyphenyl)ethanone (intermediate 1) and 4-methoxybenzoyl halide, performing demethylation protection, and preparing raloxifene hydrochloride from the demethylated raloxifene hydrochloride precursor and hydrochloricacid. Herein, the intermediate 1 is generated by removing benzyl protection from an intermediate 3 (1-{4-[2-(piperidine-1-yl)ethoxy]phenyl}-2-(2-benzylthio-4-methoxyphenyl)ethanone) in trifluoroacetic acid through a reaction; (3-methoxyphenyl) benzyl sulfide is oxidized to generate a sulfoxide compound, and then the sulfoxide compound reacts with 1-[2-(4-ethynylphenoxy)ethyl]piperidine to generate an intermediate 3. The method has the advantages of mild reaction conditions, few side reactions, high yield, cheap reagent raw materials, easy recovery and easy preparation, and is suitable for industrial large-scale production.
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- Novel solvated crystalline of Raloxifene hydrochloride and process for preparing Raloxifene hydrochloride monohydrate
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The present invention relates to a raloxifene hydrochloride acetone solvate which is a novel solvate of raloxifene hydrochloride, namely, [6-hydroxy-2-(4-hydroxyphenyl)-benzo thiophen-3-yl]-[4-[2-(1-piperidyl)ethoxy]phenyl]-methanone hydrochloride; and a method to manufacture high purity raloxifene hydrochloride monohydrate using the same. The manufacturing method of raloxifene hydrochloride monohydrate comprises the following steps: a) make a crystalline raloxifene hydrochloride acetone solvate into a slurry in top water; b) adding and mixing concentrated hydrochloric acid into the solution; and c) obtaining raloxifene hydrochloride monohydrate by separating solids obtained from the step b) and drying the solids.COPYRIGHT KIPO 2016
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Paragraph 0045; 0047
(2016/10/09)
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- PROCESS FOR THE PREPARATION OF RALOXIFENE HYDROCHLORIDE
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The present invention provides an improved process for the preparation of α-(3- methoxyphenylthio)-4-methoxyacetophenone. The present invention also provides a process for the preparing free flowing solid of 6-methoxy-2-(4-methoxyphenyl)- benzo[b]-thiophene. The present invention further provides a process for the preparation of substantially pure 6-methoxy-2-(4-methoxyphenyl)-benzo[b]-thiophene. The present invention further provides a process for purification of raloxifene hydrochloride.
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- A PROCESS FOR PREPARING BENZO[B]THIOPHENE DERIVATIVES
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The present invention relates in general to the field of organic chemistry, and in particular to the preparation of benzo[b]thiophene derivatives. These benzo[b]thiophene derivatives are useful as intermediates in the synthesis of pharmaceutically active agents such as raloxifene or derivatives thereof.
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- PREPARATION OF RALOXIFENE AND ITS SALTS
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The invention provides processes for the preparation of pure raloxifene or its salts, involving hydrolyzing 6-methylsulfonyloxy-2-[(4-methylsulfonyloxy)-phenyl]-3-[4(2-(piperidinyl)ethoxy)benzoyl]benzothiophene hydrochloride, using an aqueous base.
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Page/Page column 7; 8
(2011/04/14)
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- A process for preparing benzo[b]thiophene derivatives
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The present invention relates in general to the field of organic chemistry, and in particular to the preparation of benzo[b]thiophene derivatives. These benzo[b]thiophene derivatives are useful as intermediates in the synthesis of pharmaceutically active agents such as raloxifene or derivatives thereof.
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Page/Page column 34
(2011/06/10)
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- A PROCESS FOR PREPARING BENZO[B]THIOPHENE DERIVATIVES
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The present invention relates in general to the field of organic chemistry, and in particular to the preparation of benzo[b]thiophene derivatives. These benzo[b]thiophene derivatives are useful as intermediates in the synthesis of pharmaceutically active agents such as raloxifene or derivatives thereof.
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Page/Page column 52-53
(2011/05/06)
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- A PROCESS FOR THE PREPARATION OF 6-HYDROXY-2-(4-HYDROXYPHENYL)-3-[4-(2-PIPERIDINO ETHOXY) BENZOYL]BENZO[B]THIOPHENE
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The present invention related to a process for preparing 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2- piperidinoethoxy)benzoyl]benzo[b]thiophene, compound of formula (I), said process comprising: deprotecting compound of formula (II) with base in dimethyl sulfoxide to yield substantially pure compound of formula (I) with HPLC purity of 99 % or more by area and optionally converting to its pharmaceutically acceptable salt.
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Page/Page column 14
(2009/03/07)
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- CRYSTALLINE FORM OF BENZOTHIOPHENE COMPOUND AND PROCESS FOR PREPARATION THEREOF
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Crystalline raloxifene hydrochloride in hydrated form, particularly the monohydrate, processes for its preparation, pharmaceutical compositions comprising it and uses thereof.
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Page/Page column 15
(2008/12/05)
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- Process for preparing benzoic acids
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An improved process for the preparation of 4[(2-piperidin-1-yl)ethoxy]benzoic acid derivatives, comprising reacting a haloalkyl amine of formula (III) with a compound of formula (IV) in the presence of a hydrated inorganic base in an appropriate solvent.
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Page/Page column 7
(2010/02/12)
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- PROCESS FOR PREPARING RALOXIFENE HYDROCHLORIDE
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Process for preparing raloxifene hydrochloride with a purity greater than 98% and low aluminium content comprising the following stages a) demethylation of 6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene in pyridine and hydrochloric acid to obtain 6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thiophene in pyridine hydrochloride, b) acetylation of 6-hydroxy-2-(4-hydroxyphonyl)benzo[b]thiophene with an acetylating agent to obtain the corresponding 6-acetoxy-2-(4 acetoxyphenyl)benzo[b]thiophene, c) acylation of 6-acetoxy-2-(4-acetoxyphonyl)benzo[b]thlophene with 4-(2 piperidinoethoxy)benzoylchloride hydrochloride with aluminium trichloride in halogenated solvent to obtain 6-acetoxy-2-(4-acetoxyphenyl)-3-[4-(2 piperidinoethoxy)benzoyl]-benzo[b]thiophene, d) hydrolysis of 6-acetoxy-2-(4-acetoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyll benzo[b]thiophene according to the following operating conditions: dl) treatment of 6-acetoxy-2-(4-acetoxyphonyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene with alkaline hydroxide in alcohol solvent, d2) acidification of the product obtained in the preceding stage (dl) with a strong acid, to obtain the corresponding raloxifene salt with the strong acid, characterised in that the strong acid used in stage (d2) is concentrated hydrochloric acid.
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- Benzothiophenes formulations containing same and methods
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This invention provides compounds of formula I and pharmaceutically acceptable salts and solvates thereof, characterized that the compound is in particulate form and having a specific size range. The present invention further provides pharmaceutical compositions containing or formulated using compounds of formula I, and the use of such compounds for alleviating human pathologies, including osteoporosis, serum lipid lowering, and breast cancer.
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- Process for the synthesis of vinyl sulfoxides
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The present invention is directed to a new process for the synthesis of vinyl sulfoxides, in particular diarylvinyl sulfoxides
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Page column 16-17
(2010/01/31)
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- Methods of treating nueropeptide Y-associated conditions
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This invention describes methods of treating conditions associated with an excess of neuropeptide Y which comprises administering an obesity protein. This invention also describes methods of treating conditions associated with an excess of neuropeptide Y which comprises administering an obesity protein in combination with a neuropeptide Y antagonist. This invention demonstrates that the obesity protein acts by reducing the production of neuropeptide Y by the hypothalamus.
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- Process for preparing benzo[b]thiophenes
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The preparation of benzo[b]thiophenes by the acylation of alkoxy protected starting materials followed by demethylation using essentially odorless thiol compounds are provided herewith. Demethylation may be carried out in the same reaction vessel without isolation of the acylated, protected material.
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- Synthesis of 3-[4-(2-aminoethoxy)-benzoyl]-2-aryl-6-hydroxy-benzo[B]thiophenes
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The present invention is directed to chemical processes for preparing 2-aryl-6-hydroxy-3-[4-(2-aminoethoxyl)benzoyl]benzoyl]benzo[b]-thiophenes.
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- Demethylation process for preparing benzo[b]thiophenes
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The preparation of benzo[b]thiophenes by the acylation of alkoxy protected starting materials followed by demethylation using essentially odorless thiol compound (2-methyl-5-t-butyl benzenethiol) are provided herewith. Demethylation may be carried out in the same reaction vessel without isolation of the acylated, protected material.
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- Haloalkyl hemisolvates of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-piperidinoethoxy)-benzoyl]benzo[b]thiophene
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The present invention is directed to chemical processes for preparing 2-aryl-6-hydroxy-3-[4-(2-aminoethoxy)benzoyl]benzo[b]thiophenes. The present invention is also directed to crystalline solvates and a non-solvated crystalline form of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene hydrochloride, as well as processes for their preparation.
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- Glucopyranoside benzothiophenes
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A compound of the formula STR1 or a pharmaceutically acceptable salt or solvate thereof. Also provided by the invention are methods of use of the above compounds, and processes for the preparation thereof.
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- Methods of use for inhibiting bone loss and lowering serum cholesterol
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A method of inhibiting bone loss or resorption, or lowering serum cholesterol, comprising administering to a human in need thereof a compound having the formula STR1 or a pharmaceutically acceptable salt or solvate thereof, in a low dosage amount. Also encompased by the invention is a a pharmaceutical formulation in unit dosage form comprising, per unit dosage, a low dosage amount.
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- Treatment of mammary cancer
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Mammary cancers are inhibited by administration of a combination of two drugs. The first compound is 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-pyrrolidinoethoxy)benzoyl]benzo[b]thiophene, and the second compound is tamoxifen.
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- Antiestrogens. 2. Structure-Activity Studies in a Series of 3-Aroyl-2-arylbenzothiophene Derivatives Leading to thien-3-yl>phenyl>methanone Hydrochloride (LY156758), a Remarkably Effective Estrogen Antagonist with On...
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In an effort to prepare nonsteroidal antiestrogens demonstrating greater antagonism and less intrinsic estrogenicity than those currently available, a series of 3-aroyl-2-arylbenzothiophene derivatives was synthesized.These compounds were prepared by Friedel-Crafts aroylation of appropriate O-protected 2-arylbenzothiophene nuclei with basic side-chain-bearing benzoyl chlorides followed by removal of the protective groups to provide the desired compounds containing both hydroxyl and basic side-chain functionality.A particularly useful method for the cleavage of aryl methoxy ethers without removal of (dialkylamino)ethoxy side chain functionality elsewhere in the molecule was found to be AlCl3/EtSH.The benzothiophene derivatives were tested for their ability to inhibit the growth-stimulating action of estradiol on the immature rat uterus.Seemingly minor changes in the side-chain amine moiety were found to have profound effects on the ability of the compounds to antagonize estradiol.Analogues having basic side chains containing cyclic (pyrrolidine, piperidine, and hexamethyleneamine) moieties were found to have less intrinsic estrogenicity and to antagonize estradiol action more completely than their noncyclic counterparts.The most effective antiestrogen in the series, compound 44, thien-3-yl>phenyl>methanone, elicited a modest uterotropic activity that did not increase with increasing dose.In antagonism of estradiol, 44 exhibited a degree of inhibition surpassing that of tamoxifen at any dose tested.The new benzothiophene antiestrogen was also shown to have high affinity for rat uterine cycloplasmic estrogen receptor and to be an inhibitor of the growth of DMBA-induced rat mammary tumors.
- Jones, Charles D.,Jevnikar, Mary G.,Pike, Andrew J.,Peters, Mary K.,Black, Larry J.,at al.
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p. 1057 - 1066
(2007/10/02)
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- Synthesis of acylated benzothiophenes
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A group of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-aminoethoxy)benzoyl]benzo[b]thiophenes are prepared by acylation of a methyl-protected starting compound followed by demethylation in a single reaction mixture.
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- Antiestrogenic and antiandrugenic benzothiophenes
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6-Hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, its ethers and esters, and the physiologically acceptable acid addition salts thereof, are valuable antiestrogens and antiendrogens.
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