- A method of preparation he male amine
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The invention belongs to the field of pharmaceutical chemistry, and relates to a high-yield method for preparing dutasteride, which comprises the following steps: (1) under the action of a catalyst, reacting aza-5-androst-1-alkenyl-3-keto-17beta-carboxylic acid (I) with alcohol to generate 4-aza-5-androst-1-alkenyl-3-keto-17beta-carboxylate (II); and (2) in the presence of a catalyst, reacting the 4-aza-5-androst-1-alkenyl-3-keto-17beta-carboxylate (II) with 2,5-ditrifluoromethylaniline in an organic solvent at certain reaction temperature to obtain the dutasteride (III) at high yield. The method has the characteristics of accessible raw material, mild reaction conditions and high product yield, and is easy to control.
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Paragraph 0012-0013
(2018/09/26)
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- Production process of high-purity dutasteride
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The invention discloses a purification production process of high-purity dutasteride. The problems to be solved are that the purity of the dutasteride is improved while the production cost is reduced.According to the method, after a dutasteride crude product is obtained, twice crystallization is carried out, so that the dutasteride with high yield and high purity can be obtained. The production process provided by the invention has the advantages of high efficiency and clean production, and the operability is high. An intermediate is refined, so that the quality of the dutasteride finished product is more easily controlled, the purity of the obtained dutasteride product is not lower than 99.5%, and any single impurity in the product is not higher than 0. 1%.
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Paragraph 0046; 0047; 0053-0055; 0058-0060; 0069-0077
(2018/04/02)
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- Preparation method of dutasteride
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The invention relates to a preparation method of dutasteride. The preparation method comprises the following steps: dissolving 3-keto-4-aza-5-alpha-androst-1-ene-17beta carboxylic acid into an organic solvent, adding dichlorosulfane, performing a reaction
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Paragraph 0017; 0028; 0029; 0032
(2017/06/29)
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- A high-pure undistilled he male amine preparation method (by machine translation)
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The invention discloses a high-pure undistilled he male amine preparation method, the dutasteride in acetonitrile residue is ≤ 0.04%, type V impurity residual ≤ 0.02%, total impurity ≤ 0.15%. The preparation method comprises dutasteride crude synthesis an
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Paragraph 0064
(2017/08/29)
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- A androst - 17β - N - (2, 5 - (trifluoromethyl)-) IBZM preparation method
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The invention provides a preparation method of androstane-17beta-N-(2,5-bis (trifluoromethyl)) benzamide. The preparation method comprises the following steps: (1) in the presence of an acid-binding agent, carrying out acyl chloride forming reaction between androstane-17beta carboxylic acid and thionyl chloride to obtain androstane-17beta acyl chloride; (2) enabling the androstane-17beta acyl chloride and 2,5-bis(trifluoromethyl) aniline to generate amide forming reaction in the presence of a hydrogen stripping agent to obtain androstane-17beta-N-(2,5-bis (trifluoromethyl)) benzamide, wherein the acid-binding agent is anhydrous potassium carbonate fine powder. The preparation method disclosed by the invention can be used for simply preparing the androstane-17beta-N-(2,5-bis (trifluoromethyl)) benzamide with low toxicity, high quality, high yield and low cost.
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Paragraph 0039; 0040; 0041; 0046; 0047
(2018/01/02)
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- A kind of dutasteride impurities method for the preparation of I
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The invention belongs to the technical field of medicines and discloses a preparation method of a dutasteride impurity I. The preparation method of the dutasteride impurity I comprises the following steps: preparing a compound III refined product, carryin
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Paragraph 0046; 0047
(2017/02/23)
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- Method for forming double bonds between 1-position and 2-position during synthesis of finasteride and dutasteride
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The invention provides a method for forming double bonds between the 1-position and the 2-position during synthesis of finasteride and dutasteride. According to the process, a dihydrogen finasteride iodide and a dihydrogen dutasteride iodide are oxidized by oxone for systhesis of finasteride and dutasteride, and the method has the characteristics that reaction operation is simple and convenient, raw materials are low in price and easy to obtain, and the yield and the purity are high. In particular, oxone is non-toxic, stable, easy to operate and more suitable for large-scale industrial production, and reagents which are harmful to the environment and high in price are avoided. The method can be further applied to forming of double bonds between the 1-position and the 2-position of an intermediate in other finasteride and dutasteride processes. The invention further provides a synthesis method of dihydrogen dutasteride; according to the method, a corresponding ester raw material has a one-pot reaction with 2,5-bis(trifluoromethyl)aniline under the activation of boron tribromide, and dihydrogen dutasteride with the yield of 93% is obtained.
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- A process for the preparation of dutasteride
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The invention belongs to the technical field of medicine, and provides a preparation method of dutasteride. The preparation method comprises the following steps: A) an industrial-grade compound III is washed by acetone after beaten and refined by formic acid, and a refined compound III product is obtained; B) the refined compound III product has a chlorination reaction to generate a compound II; C) the compound II has a condensation reaction with 2,5-bis (trifluoromethyl) phenylamine, a product is cooled and filtered, a filtrate is collected, a hydrochloric acid solution is added for washing, an organic phase is separated, pressure is reduced to evaporate s solvent, and a crude dutasteride product is obtained; and D) the crude dutasteride product is dissolved by an organic solvent and decolorized, an anti-solvent is added for crystallization, and high-purity dutasteride is obtained. Side reactions are reduced, high-purity dutasteride can be obtained through preparation, and the productive cost is reduced.
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Paragraph 0055; 0056; 0062
(2017/03/08)
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- PROCESS FOR THE SYNTHESIS OF (5α,17β)-N-[(2,5-BIS(TRIFLUOROMETHYL)-PHENYL]-3-OXO-4-AZA-5-ANDROST-1-ENE-17-CARBOXAMIDE
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The synthesis consists of reaction steps as follows: oxidizing the α,β-unsaturated ketone system of ring "A" of pregn-4-ene-3,20-dion- of formula (II) with sodium metaperiodate in tert-butanol in the presence of potassium permanganate and alkali metal carbonate, reacting the obtained 3,5-seco acid with an ester of chloroformic acid in the presence of tertier organic base below 0°C, reacting the obtained new compound after isolation or without isolation with ammonia or ammonium acetate, cyclization of the resulting carboxamides with an acid, cathalytic hydrogenating the obtained ene lactame, and oxidizing the side chain at position 17 of the obtained pregnane compound with an alkali metal hypobromide in aqueous dioxane below 10°C. Thereafter on one hand the obtained (5α,17β)-3-oxo-4-aza-5-androstane-17-carboxylic acid is reacted with chloroformic acid ester, the obtained new compound is reacted with 2,5-bis(trifluoromethyl)-aniline in the presence of a Lewis acid, the obtained amide is reacted with trimethyl chlorosilane in inert atmosphere in the presence of Ν,Ν,Ν',Ν'-tetramethyl-ethylendiamine, then en excess iodine is added to the reaction mixture and the product of the iodination reaction is crystallized from acetonitrile, then the obtained 2-iodo-3-oxo-4-aza-17β-carboxamide is reacted with potassium tert-butylate to furnish final product. On the other hand, (5α,17β)-3-oxo-4-aza-5-androstane-17-carboxylic acid is transformed into methylester by known method, this latter is transformed into methyl (2α,5α,17β)-2-iodo-3-oxo-4-aza-5-androstane-17-carboxylate according to known method, the obtained compound is reacted with potassium-tert-butylate, the obtained (5α,17β)-3-oxo-4-aza-5-androst-1-ene-17-carboxylic acid is reacted with an ester of chloroformic acid, then the obtained new compound is coupled with 2,5-bis(trifluoromethyl)-aniline in the presence of a Lewis acid catalyst to gain final product.
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- PROCESS FOR THE PREPARATION OF DUTASTERIDE
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The present invention provides an improved process for the preparation of Dutasteride (I) which comprises: (i) reacting 4-aza-5α-androst-1-en-3-one-17β-carboxylic acid (VII), Formula VII with sulfonic acid anhydride (RSO2)2O in presence of base to produce an intermediate compound of Formula (XIII), wherein R represents C1-6 alkyl, C1-6 halo alkyl, C6-10 aryl, halo aryl; (ii) condensing compound of Formula (XIII) with 2,5-bis(trifluoromethyl)aniline (III), Formula (III) in the presence or absence of a base to produce Dutasteride (I).
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Page/Page column 6
(2012/06/30)
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- PROCESS FOR PREPARING ANDROSTENONE DERIVATIVES
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Provided is a process for preparing androstenone derivatives, specifically 3-oxo-4-aza-5α-androstene-17β-carboxylic acid of Formula I, a key intermediate for dutasteride.
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- Pharmaceutical composition comprising dutasteride
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The invention relates to a pharmaceutical composition comprising (a) at least one active ingredient selected from dutasteride or a pharmaceutically acceptable salt or solvate thereof and (b) a solubilizer.
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- PURIFICATION 4-AZA-ANDROST-1-ENE-17-OIC ACID FROM 4-AZA-ANDROSTAN-17-OIC ACID
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The present invention relates to a process of separation of 4-aza-androst-1-ene-17-oic acid from 4-aza-androstan-17-oic acid, which brings to 4-aza-androst-1-ene-17-oic containing less than 0.05% w/w of 4-aza-androstan-17-oic acid, with high yield and pro
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Page/Page column 4
(2012/02/06)
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- PURIFICATION 4-AZA-ANDROST-1-ENE-17-OIC ACID FROM 4-AZA-ANDROSTAN-17-OIC ACID
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The present invention relates to a process of separation of 4-aza-androst-1-ene-17-oic acid from 4-aza-androstan-17-oic acid, which brings to 4-aza-androst-1-ene-17-oic containing less than 0.05% w/w of 4-aza-androstan-17-oic acid, with high yield and productivity. In particular, the present invention relates to a process for the separation of 4-aza-androstan-17-oic acid from 4-aza-androst-1-ene-17-oic acid, comprising the steps of treating the crude 4-aza-androst-1-ene-17-oic acid with formic acid and recovering the purified 4-aza-androst-1-ene-17-oic acid containing 4-aza-androstan-17-oic acid in w/w% less than 0,05%.
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Page/Page column 12-13
(2010/11/03)
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- SOLID AND CRYSTALLINE DUTASTERIDE AND PROCESSES FOR PREPARATION THEREOF
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The present invention relates to a synthetic process for manufacturing Dutasteride comprising the mixed anhydride formation, subsequent reaction with 2,5- bis(trifluoromethyl)phenylamine in the presence of an appropriate Lewis catalyst and its isolation,
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Page/Page column 17
(2009/08/14)
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- A scaleable synthesis of dutasteride: A selective 5α-reductase inhibitor
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An improved and scaleable process for Dutasteride (1), a synthetic 4-azasteroid derivative essentially used for the treatment of prostate diseases, is described
- Satyanarayana, Komati,Srinivas, Katkam,Himabindu, Vurimidi,Reddy, Ghanta Mahesh
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p. 842 - 845
(2012/12/30)
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- Process for the preparation of 17beta-N-[2,5-bis(trifluoromethyl)phenyl] carbamoyl-4-aza-5-alpha-androst-1-en-3-one
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The present invention relates to a process for the preparation of Dutasteride, which is chemically known as 17β-N-[2,5-bis (trifluoromethyl) phenyl] carbamoyl-4-aza-5-α-androst-1-en-3-one and can be represented by Formula (I).
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Page/Page column 2; 4; 5
(2008/06/13)
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