- Preparation method of indacaterol and salt thereof
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The invention relates to a preparation method of indacaterol and a salt thereof. The preparation method comprises the following steps: in a solvent, reacting a mixture containing a compound as shown in a formula I with m-chlorobenzoic acid to obtain a com
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Paragraph 0049-0051; 0055-0058; 0061-0062; 0065-0068
(2020/11/01)
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- A maleic acid yin dutrow intermediate and its preparation and use
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The invention relates to maleic acid yin dutrow intermediate (R)- 8 - (benzyloxy) - 5 - [2 - [(5, 6 - diethyl - 2, 3 - dihydro - 1 H - indene - 2 - yl) amino] - 1 - hydroxy ethyl] quinoline - 2 (1 H) - one a new salt and its crystalline form, the salt and its crystalline form has good impurity removing effect and thermodynamic stability, the preparation method is simple, the operation is facilitated and the storage, is suitable for industrial application. The invention also relates to the new salt and its crystal preparation method, and process for the preparation of maleic acid yin dutrow use.
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Paragraph 0061-0062
(2019/05/16)
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- Preparation method for indacaterol maleate
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The invention specifically relates to a preparation method for indacaterol maleate, belonging to the field of drug synthesis. The preparation method is simple and short in steps, easy to operate, safe, friendly to environment and fee of an alkaline solution; after a heating reaction, a coupled product in the step 1) can be obtained, and the amount of produced regioisomers, dimers and other by-products is small; the yield of the product indacaterol maleate is high, as high as 93%, and the HPLC purity of the product indacaterol maleate is more than 97.8%; post-treatment is simple, and industrialproduction of indacaterol maleate is facilitated; and the product indacaterol maleate is high in optical purity.
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- A Process for Preparing Indacaterol and Salts Thereof
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The present invention relates to a process for preparing indacaterol or salts thereof. The process comprises of forming compound of Formula 1 by reacting compound of Formula 2 and compound of Formula 3 in the presence of a solvent to Form compound of Formula 4, which on removal of the protecting groups forms compound of Formula 1.
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- A new method of [...]dutrow
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The present invention discloses a new method for synthesizing indacaterol. The present invention provides a completely-new indacaterol synthesis method. Compared with the known method in the prior art, the method of the present invention has the following characteristics that: the easily available starting raw material is adopted, the side reaction is less when the two raw material fragments dock, the reaction conditions of the route are mild, the route is short, the yield is high, and the market competitiveness is provided.
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Paragraph 0026; 0027; 0028
(2017/07/04)
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- dutrow[...][...] method for the synthesis of intermediates
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Disclosed is an intermediate for synthesizing indacaterol, having a structure represented by formula IV. Also disclosed are a method for synthesizing the indacaterol intermediate and a method for synthesizing indacaterol by using the intermediate. During synthesis of indacaterol, the intermediate of formula IV is reduced to obtain a chiral or racemic compound, which is then debenzylated to obtain indacaterol or a raceme thereof. By using the compound of formula IV as an intermediate for synthesizing indacaterol, the present invention provides a new route for synthesizing indacaterol, and avoids various byproducts produced in the process of synthesizing indacaterol using conventional methods.
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Paragraph 0091; 0092
(2017/05/03)
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- PROCESS FOR THE MANUFACTURE OF (R)-5-[2-(5,6-DIETHYLINDAN-2-YLAMINO)-1-HYDROXYETHYL]-8-HYDROXY-(1H)-QUINOLIN-2-ONE
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The present invention provides an efficient process for manufacturing (R)-5-[2-(5,6-diethyl-indan-2-yl-amino)-1-hydroxyethyl]-8-hydroxy-(1H)-quinolin-2-one, commonly known as indacaterol, or a pharmaceutically acceptable salt thereof, comprising intermediates of synthesis of Formula (II) and Formula (III).
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Page/Page column 52; 53
(2014/10/15)
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- A METHOD FOR THE PREPARATION OF 5-[(R)-2-(5,6-DIETHYL-INDAN-2-YLAMINO)-L-HYDROXYETHYL]- 8-HYDROXY-(1H)-QUINOLIN-2-ONE (INDACATEROL)
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The invention relates to a new method of synthesis of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)- 1-hydroxyethyl]-8-hydroxy-(1H)-quinolin-2-one of formula (R)-2, known under the generic name indacaterol, which is used for the treatment of chronic obstructive pulmonary disease (COPD). The method comprises preparation of the racemic intermediate 5-[2-(5,6-diethyl-indan-2-ylamino)-1-hydroxyethyl]-8-benzyloxy-(1H)-quinolin-2-one of formula 1, which is further, in an arbitrary order, chirally resolved and debenzylated, and subsequently indacaterol of formula (R)-2 is isolated.
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Page/Page column 9; 10
(2014/09/29)
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- CONTINUOUS FLOW SYNTHESIS OF AMINO ALCOHOLS USING MICROREACTORS
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The present invention provides various methods for the synthesis of chemical species in a microreactor environment. In some cases, reaction products of the present invention may be valuable as intermediates and/or products in pharmaceutical and polymer research. For example, the method may involve the synthesis of amino alcohols within a microchannel. Embodiment described herein may allow for reactions with significantly shorter reaction times and increased efficiency.
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Page/Page column 12-13
(2011/06/10)
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- Aminolysis of epoxides in a microreactor system: A continuous flow approach to β-Amino alcohols
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The use of a continuous flow microreactor for β-amino alcohol formation by epoxide aminolysis is evaluated. Comparison to microwave batch reactions reveals that conditions obtainable in the microreactor can match or improve yields in many cases. By increasing the pressure of the system, maximum temperatures can also exceed those accessible using a microwave unit. The use of a microreactor for epoxide aminolysis reactions in the synthesis of two pharmaceutical relevant compounds is described.
- Jensen, Klavs F.,Bedore, Matthew W.,Zaborenko, Nikolay,Jamison, Timothy F.
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experimental part
p. 432 - 440
(2011/04/22)
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- The identification of indacaterol as an ultralong-acting inhaled β2-adrenoceptor agonist
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Following a lipophilicity-based hypothesis, an 8-hydroxyquinolinone 2-aminoindan derived series of β2-adrenoceptor agonists have been prepared and evaluated for their potential as inhaled ultralong-acting bronchodilators. Determination of their activities at the human β2-adrenoceptor receptor showed symmetrical substitution of the 2-aminoindan moiety at the 5- and 6-positions delivered the targeted intermediate potency and intrinsic-efficacy profiles relative to a series of clinical reference β2-adrenoceptor agonists. Further assessment with an in vitro superfused electrically stimulated guinea-pig tracheal-strip assay established the onset and duration of action time courses, which could be rationalized by considering the lipophilicity, potency, and intrinsic efficacy of the compounds. From these studies the 5,6-diethylindan analogue indacaterol 1c was shown to possess a unique profile of combining a rapid onset of action with a long duration of action. Further in vivo profiling of 1c supported the long duration of action and a wide therapeutic index following administration to the lung, which led to the compound being selected as a development candidate.
- Baur, Fran?ois,Beattie, David,Beer, David,Bentley, David,Bradley, Michelle,Bruce, Ian,Charlton, Steven J.,Cuenoud, Bernard,Ernst, Roland,Fairhurst, Robin A.,Faller, Bernard,Farr, David,Keller, Thomas,Fozard, John R.,Fullerton, Joe,Garman, Sheila,Hatto, Julia,Hayden, Claire,He, Handan,Howes, Colin,Janus, Diana,Jiang, Zhengjin,Lewis, Christine,Loeuillet-Ritzler, Frederique,Moser, Heinz,Reilly, John,Steward, Alan,Sykes, David,Tedaldi, Lauren,Trifilieff, Alexandre,Tweed, Morris,Watson, Simon,Wissler, Elke,Wyss, Daniel
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supporting information; experimental part
p. 3675 - 3684
(2010/07/16)
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- A PROCESS FOR THE PREPARATION OF 5-(HALOACETYL)-8-(SUBSTITUTED OXY)-(1H)-QUINOLIN-2-ONES
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The invention relates to a process for preparing 5-(α-haloacetyl)-8-substituted oxy-(1H)-quinolin-2-ones. The process involves (i) reacting (a) 8-hydroxy-(1H)-quinolin-2-one with an acylating agent and a Lewis acid to form 5-acetyl-8-hydroxy-(1H)-quinolin-2-one; or (b) 8-hydroxy-(lH)-quinolin-2-one with an acylating agent to form 8-acetoxy-(lH)-quinolin-2-one, and treating, in-situ, the 8-acetoxy-(1H)-quinolin-2-one with a Lewis acid to form 5-acetyl-8-hydroxy-(1H)-quinolin-2-one; or (c) 8-acetoxy-(1H)-quinolin-2-one with a Lewis acid to form 5-acetyl-8-hydroxy-(lH)-quinolin-2-one; (ii) reacting the 5-acetyl-8-hydroxy-(1H)-quinolin-2-one prepared in Step (i) with a compound having the Formula RL in the presence of a base and a solvent to form 5-acetyl-8-substituted oxy-(1H)-quinolin-2-one, wherein R is a protecting group and L is a leaving group; and (iii) reacting the 5-acetyl-8-substituted oxy-(1H)-quinolin-2-one with a halogenating agent in the presence of a solvent to form a 5-(α-haloacetyl)-8-substituted oxy-(1H)-quinolin-2-one.
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