cas 136236-51-6, Rasagiline | Articles data

Articles about 136236-51-6Total 37 be found

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A validated normal phase LC method for enantiomeric separation of rasagiline mesylate and its (S)-enantiomer on cellulose derivative-based chiral stationary phase
A simple, sensitive, and robust normal-phase isocratic HPLC-UV method was developed and validated for the enantiomeric separation of rasagiline mesylate and its (S)-enantiomer. The rasagiline and its (S)-enantiomer were resolved on a Chiralcel-OJ-H (4-methylbenzoate cellulose coated on silica) column using a mobile phase consisting of n-hexane:isopropyl alcohol:ethanol:diethyl amine (96:2:2:0.01) at a flow rate of 1.0 ml/min. The column temperature was maintained at 27 °C and elution was monitored at 215 nm. The resolution (Rs) between the enantiomers was found to be more than 2.0. The limit of detection and the limit of quantification of the (S)-enantiomer were found to be 0.35 and 1.05 μg/ml, respectively. The developed method was validated as per ICH guidelines with respect to linearity, limit of detection and quantification, accuracy, precision, and robustness - and satisfactory results were obtained. The sample solution and mobile phase were found to be stable up to 48 h. The method is useful for routine evaluation of the quality of rasagiline mesylate in bulk drug-manufacturing units.
Sunil Reddy,Sudhakar Babu,Kumar, Navneet
p. 324 - 327
(2013)
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Identification and genotoxicity evaluation of two carbamate impurities in rasagiline
During the synthesis of a second-generation monoamine oxidase-B inhibitor rasagiline, two unknown impurities (impurity A and impurity B) were detected and isolated by preparative liquid chromatography. Based on mass spectroscopy and NMR, these two impurities were characterized as the by-products with a propargyl carbamate structure, whose generation was related to the carbon dioxide in the alkaline reaction solution. Because the carbamate structure has been highlighted as a class of potentially genotoxic impurities (GTIs), the genotoxicity of these two impurities was evaluated by the malformation test and the comet assay using zebrafish embryos. The results showed that the genotoxicity of impurity B was significant higher than that of rasagiline and other impurities. Thus, a HPLC-MS method was developed and validated for the determination of impurity B in rasagiline. The established method showed a good specificity, linearity, precision and accuracy. The detection limit of this method was 2.0?ppm with 0.1 mg ml?1 rasagiline mesylate.
Sun, Yongqiang,Zhang, Xinyu,Yan, Yimin,Tu, Yongrui,Feng, Xiaohui,Jiang, Wei,Zheng, Feng
p. 106268 - 106274
(2016)
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Enantioselective synthesis of 1-aminoindene derivativesviaasymmetric Br?nsted acid catalysis
We describe a catalytic asymmetric iminium ion cyclization reaction of simple 2-alkenylbenzaldimines using a BINOL-derived chiralN-triflyl phosphoramide. The corresponding 1-aminoindenes and tetracyclic 1-aminoindanes are formed in good yields and high enantioselectivities. Further, the chemical utility of the obtained enantiopure 1-aminoindene is demonstrated for the asymmetric synthesis of (S)-rasagiline.
Ding, Du,Jiang, Hua-Jie,Wang, Tao,Wu, Xiang,Zhang, Ying,Zhao, Li-Ping
supporting information
p. 9680 - 9683
(2021/09/30)

Improved method for preparing rasagiline
The invention provides an improved method for preparing rasagiline, which comprises the following steps: by using a micro-channel reactor, reacting R-(-)-1-aminoindane (structural formula II) servingas a raw material with a propargyl derivative (structural formula III) in the presence of a proper solvent, temperature, alkali and the like to obtain R-(+)-N-propargyl-1-aminoindane (structural formula I), and salifying to obtain rasagiline mesylate. The reaction formula is shown in the specification. According to the method, a dialkyl substitution by-product N,N-dipropargyl-1-aminoindane can bereduced, the rasagiline and the salt thereof can be prepared with a high yield and high purity, the reaction time is shortened, the reaction conditions can resist high temperature and high pressure, the post-treatment is simple, the dialkyl substitution by-product is easy to remove, the unreacted R-(-)-1-aminoindane can be separated and recycled, and the cost is low, and the method is suitable forindustrial production.
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Paragraph 0031-0041

(2020/07/12)

Preparation method of rasagiline mesylate and intermediate thereof
The invention discloses a preparation method of rasagiline mesylate and an intermediate thereof. The invention provides the preparation method of rasagiline mesylate I. The preparation method comprises the following steps: S1, in an organic solvent, in the presence of a reducer and a catalyst, carrying out a reduction reaction on a rasagiline mesylate intermediate II and the reducer to obtain a rasagiline mesylate intermediate III; and S2, in an organic solvent, carrying out a salt forming reaction on the rasagiline mesylate intermediate III obtained in the S1 and methanesulfonic acid to obtain rasagiline mesylate I. The preparation method does not employ an amino alkylation reaction which is relatively more in side reaction, and the prepared rasagiline mesylate I is high in purity, reaches the demand on bulk pharmaceutical chemicals, the purity is greater than 99.5%, the maximum single impurities are smaller than 0.10%, the yield is high, the production cost is low, and the method issuitable for industrial production. The formula is as shown in the description.
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Paragraph 0073-0079

(2019/01/21)

CHIRAL CATALYST AND METHOD FOR ASYMMETRIC REDUCTION OF AN IMINE
The present disclosure discusses (i) a compound having a chemical formula according to Formula (I), or its enantiomer; and (ii) a compound that is reactive with a hydride to produce a compound having a chemical formula according to Formula (I), or its enantiomer. Formula (I) is: Formula (I) where R1 and R2 are H, optionally substituted C1-C3 alkyl, or linked together to form an optionally substituted C3 or C4 alkyl group; R3 and R3' are H; R4 and R4' are the same, and are optionally substituted C1-C6 alkyl; and R5 and R5' are the same, and are optionally substituted aryl or heteroaryl. In some examples, R4 and R5 are linked, and R4' and R5' are linked, where both linking groups are the same. The present disclosure also discusses methods of asymmetric reduction of an imine, and methods of forming the catalysts and pre-catalysts.
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Paragraph 00179; 00180; 00181; 00182; 00183; 00184

(2019/04/16)

Kinetic Resolution and Deracemization of Racemic Amines Using a Reductive Aminase
The NADP(H)-dependent reductive aminase from Aspergillus oryzae (AspRedAm) was combined with an NADPH oxidase (NOX) to develop a redox system that recycles the co-factor. The AspRedAm-NOX system was applied initially for the kinetic resolution of a variety of racemic secondary and primary amines to yield S-configured amines with enantiomeric excess (ee) values up to 99 %. The addition of ammonia borane to this system enabled the efficient deracemization of racemic amines, including the pharmaceutical drug rasagiline and the natural product salsolidine, with conversions up to >98 % and >99 % ee Furthermore, by using the AspRedAm W210A variant it was possible to generate the opposite R enantiomers with efficiency comparable to, or even better than, the wildtype AspRedAm.
Aleku, Godwin A.,Mangas-Sanchez, Juan,Citoler, Joan,France, Scott P.,Montgomery, Sarah L.,Heath, Rachel S.,Thompson, Matthew P.,Turner, Nicholas J.
p. 515 - 519
(2018/02/15)

Asymmetric Imine Hydroboration Catalyzed by Chiral Diazaphospholenes
The first use of diazaphospholenes as chiral catalysts has been demonstrated with enantioselective imine hydroboration. A chiral diazaphospholene prepared in a simple three-step synthesis from commercial materials has been shown to achieve the highest enantioselectivity for the hydroboration of alkyl imines with pinacolborane reported to date. Enantiomer ratios of up to 88:12 were obtained with low (2 mol %) catalyst loadings. Twenty examples of asymmetric reduction employing this main-group catalysis protocol, including the synthesis of the pharmaceuticals ent-rasagiline and fendiline, are shown.
Adams, Matt R.,Tien, Chieh-Hung,McDonald, Robert,Speed, Alexander W. H.
supporting information
p. 16660 - 16663
(2017/12/13)

The impurity of rasagiline mesylate preparation and analysis method
The invention provides a preparation method of an impurity A, an impurity B and an impurity C of rasagiline mesylate and provides a raw medicine for applying a prepared impurity standard product to a rasagiline mesylate product and a quality analysis method of a preparation thereof. Structures of the impurities A, B and C are as shown in the specification.
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Paragraph 0007; 0013-0014; 0027

(2017/03/14)

PROCESS AND INTERMEDIATES FOR THE RACEMIZATION OF ENANTIOMERICALLY ENRICHED 1-AMINOINDANE
The present invention relates to an improved process for the racemization of (S) -1-aminoindane. (S) -1-aminoindane is formed as a side product in the process of preparation (R) -1-aminoindane by enantiomeric resolution of racemic 1-aminoindane. (R) -aminoindane is a valuable intermediate in the process of preparation of rasagiline.
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Page/Page column 31-32

(2016/08/17)

Chemoenzymatic synthesis of rasagiline mesylate using lipases
A straightforward chemoenzymatic synthesis of rasagiline mesylate has been developed. The key steps for the introduction of chirality involved kinetic enzymatic resolution with lipases via acetylation of racindanol and an inversion configuration Mitsunobu reaction of the produced (S)-indanol. Immobilized lipase from Thermomyces lanuginosus proved to be a robust biocatalyst in the kinetic resolution, leading to (S)-indanol with high selectivity (e.e. > 99%, E > 200) in just 15 min, at 35°C, in hexane, being reused for ten-times without significant loss of the activity and selectivity.
De Mattos, Marcos Carlos,De Fonseca, Thiago Sousa,Da Silva, Marcos Reinaldo,De Oliveira, Maria Da Concei??o Ferreira,De Lemos, Telma Leda Gomes,De Marques, Ricardo Araújo
p. 76 - 82
(2015/05/04)

PROCESS FOR THE PREPARATION OF ENATIOMERICALLY PURE 1-AMINOINDAN
The present invention relates to a process for the preparation of optically pure ( R) -1-aminoindan by a diastereomeric resolution of 1-aminoindan using N-acetyl-L-glutamic acid as a resolving agent. In another aspect, the invention relates to diastereomeric salts of (R) -1-aminoindan with N-acetyl-L-glutamic acid, and their use in the process for the preparation of rasagiline.
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(2015/06/03)

A novel synthesis of rasagiline via a chemoenzymatic dynamic kinetic resolution
A novel synthetic route for preparing rasagiline mesylate is presented using a dynamic kinetic resolution (DKR) as the key step, catalyzed by Candida antarctica lipase B (CALB) and a Pd nanocatalyst. The chiral intermediate (R)-2,3-dihydro-1-indanamine was obtained through the DKR of the racemic aminoindan rac-1 in high yield (>90%) and excellent enantioselectivity (>99% ee). The process could be conducted on a 73 g scale at 200 g/L. Rasagiline mesylate was synthesized in 25% overall yield and excellent enantioselectivity (99.9% ee) over 7 steps.
Ma, Guozhen,Xu, Zhongqi,Zhang, Pengfei,Liu, Jinpo,Hao, Xilin,Ouyang, Jingping,Liang, Ping,You, Song,Jia, Xian
p. 1169 - 1174
(2014/12/10)

(E)-Alkenes as replacements of amide bonds: Development of novel and potent acyclic CGRP receptor antagonists
A new class of CGRP receptor antagonists was identified by replacing the central amide of a previously identified anilide lead structure with ethylene, ethane, or ethyne linkers. (E)-Alkenes as well as alkynes were found to preserve the proper bioactive conformation of the amides, necessary for efficient receptor binding. Further exploration resulted in several potent compounds against CGRP-R with low susceptibility to P-gp mediated efflux.
Kim, June J.,Wood, Michael R.,Stachel, Shawn J.,De Leon, Pablo,Nomland, Ashley,Stump, Craig A.,McWherter, Melody A.,Schirripa, Kathy M.,Moore, Eric L.,Salvatore, Christopher A.,Selnick, Harold G.
p. 258 - 261
(2014/01/17)

NEW METHOD FOR THE SYNTHESIS OF RASAGILINE
We have developed a new method for the synthesis of Rasagiline (Formula 1) based on the alkylation of trifluoroacetyl protected aminoindan. This protection enabled us to carry out an alkylation of aminoindan with a high yield and purity under very mild conditions with a wide range of reaction conditions and reagent selection. Considering the ease, purity and high yields of introducing and removal of the trifluoroacetyl group, this approach is a highly practical and economical way for the synthesis of rasagiline or its pharmaceutically acceptable salts.
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Paragraph 0028-0029

(2014/02/16)

Process for preparation of Rasagiline and salts thereof
The present invention relates to an improved process for the preparation of Rasagiline or pharmaceutically acceptable salts thereof. The present invention also relates to Rasagiline salts, polymorphs thereof and process for preparation thereof.
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Page/Page column 16

(2014/06/11)

A PROCESS FOR THE PREPARATION OF N-PROPRAGYL 1-AMINO INDANE AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
The present invention is directed to a process for the preparation of N-propargyl 1 -amino indane and pharmaceutically acceptable salts thereof by a process comprising: a) providing a reaction mixture comprising N-propargyl-1 -amino indane and/or a salt thereof, b) purifying N-propargyl-1 -amino indane free base exclusively by selective pH adjustment and selective extraction, c) optionally isolating N-propargyl- 1 -amino indane free base or converting insitu to its pharmaceutically acceptable salt thereof.
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Page/Page column 12

(2013/04/25)

RASAGILINE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
The present invention relates to Rasagiline acid addition salts having a particle size D(90) greater than 250 microns and D(50) greater than 100 microns, with the proviso that acid addition salt is not mesylate. The invention also discloses a process for the preparation of such Rasagiline acid addition salts.
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(2012/12/13)

A NEW METHOD FOR THE SYNTHESIS OF RASAGILINE
We have developed a new method for the synthesis of Rasagiline (Formula 1) based on the alkylation of trifluoroacetyl protected aminoindan. This protection enabled us to carry out an alkylation of aminoindan with a high yield and purity under very mild conditions with a wide range of reaction conditions and reagent selection. Considering the ease, purity and high yields of introducing and removal of the trifluoroacetyl group, this approach is a highly practical and economical way for the synthesis of rasagiline or its pharmaceutically acceptable salts.
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Page/Page column 7

(2012/07/28)

METHOD FOR PRODUCING COMPOUND FOR PREPARATION OF ANTI-PARKINSON'S DISEASE DRUG
The present invention provides a method for producing a compound of formula (I), which is used for preparing anti-Parkinson's disease drugs, rasagiline and rasagiline mesylate.
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Page/Page column 4

(2011/10/02)

3-KETO-N-PROPARGYL-1-AMINOINDAN
The subject invention provides a pharmaceutical composition containing N-propargyl-1(R)-aminoindan or a pharmaceutically acceptable salt thereof, and a compound of 3-keto-N-propargyl-1-aminoindan or a salt thereof.
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Page/Page column 9-10

(2011/07/06)

Transdermal patch formulation
A method for preparing a transdermal patch comprising a substrate layer is provided, the method comprising the steps of contacting an active pharmaceutical ingredient with a retaining means to provide a composition, applying the composition obtained to a carrier material to form a substrate layer of the transdermal patch, wherein the retaining means remain within the final transdermal patch.
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(2011/04/18)

Process for preparation of rasagiline and salts thereof
The present invention relates to an improved process for the preparation of Rasagiline or pharmaceutically acceptable salts thereof. The present invention also relates to Rasagiline salts, polymorphs thereof and process for preparation thereof.
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Page/Page column 12-13

(2011/10/04)

Delayed release rasagiline formulation
Disclosed are formulations of rasagiline base which are designed to delay release of rasagiline while maintaining specific pharmacokinetic properties. Also, disclosed are rasagiline citrate salt and the use and process of manufacture thereof.
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(2010/08/22)

A PROCESS FOR THE PREPARATION OF (R)-I -AMINOINDANES
The present invention relates to a process for the preparation of the chiral compound of formula (V), wherein R1 is a C1-C6 alkyl group optionally substituted with halogens, an aryl optionally substituted, or a trialkyl silyl group, for use as an intermediate in the preparation of (R)-1-aminoindanes, helpful in the pharmaceutical field. The compound of formula (V) is a key intermediate to the preparation of (R)-1- aminoindanes, particularly Rasagiline. The invention also relates to novel compounds, which are especially useful as intermediates for the preparation of (R)-1- aminoindanes.
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Page/Page column 40

(2010/05/14)

POLYMORPHIC FORM OF RASAGILINE MESYLATE
The present invention relates to a novel crystalline form of rasagiline mesylate and a pure form of rasagiline mesylate and processes for their preparation. Further, the invention relates to pharmaceutical compositions comprising said forms and use of said compositions in the treatment of patients suffering from Parkinson's Disease, dementia, Alzheimer's Disease, depression, hyperactive syndrome, stroke, brain ischemia, neurotrauma, schizophrenia and multiple sclerosis.
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Page/Page column 9-10

(2010/04/03)

PREPARATION OF RASAGILINE AND SALTS THEREOF
The present invention relates to processes for the preparation of rasagiline mesylate. Also provided is rasagiline mesylate having 90 volume percent of the particles (D90) with sizes less than about 6 μm and processes for the preparation thereof.
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Page/Page column 23-24

(2010/07/10)

AN IMPROVED PROCESS FOR THE PREPARATION OF AMINES
The present invention relates to an improved process for the preparation of rasagiline (1) 5 and its pharmaceutically acceptable salts. In particular it relates to a process for preparing rasagiline (1) and its salts substantially free from impurities.
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Page/Page column 13 - 14

(2009/12/28)

NEW METHOD FOR OBTAINING AN AMINOINDAN MESYLATE DERIVATIVE
The invention relates to processes for preparing rasagiline mesylate that avoid the use of alcohol solvents, thereby producing rasagiline mesylate free of any alkyl mesylates, including isopropyl mesylate. The invention further relates to processes for purifying rasagiline mesylate to obtain a product free of alkyl mesylates, and to the thus obtained rasagiline mesylate.
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Page/Page column 3-4

(2009/12/05)

PROCESS FOR THE SYNTHESIS OF PROPARGYLATED AMINOINDAN DERIVATIVES
A process for preparing a compound of formula (V) or its enantiomer, which comprises: (a) reacting racemic aminoindan of formula (II) or its enantiomer with allylhalide in presence of a base and an organic solvent at a temperature ranging from 25 C to the reflux temperature of the solvent to give compound of formula (III) (b) reacting the compound (III) with halogenating agent in a suitable organic solvent to give a dihalo compound of formula (IV) (c) treating the dihalo compound (IV) with a suitable base to give compound (V).
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Page/Page column 10-11

(2009/07/25)

Process for preparing and drying solid rasagiline base
Disclosed is crystalline R(+)-N-propargyl-l-aminoindan containing water at an amount of less than 0.5% by weight and a pharmaceutical composition comprising the same, and the process for the manufacture and the validation thereof. Also disclosed is a process for the preparation of solid rasagiline base.
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Page/Page column 6-7

(2009/12/28)

Crystalline solid rasagiline base
The subject invention provides crystalline R(+)-N-propargyl-1-aminoindan, pharmaceutical compositions and methods of manufacture thereof.
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Page/Page column 3

(2008/12/06)

Catalysts for use in enantioselective synthesis
Disclosed are compounds having the following formula: in which Z11 is selected from a substituted or unsubstituted saturated adamantyl or other polycyclic group and a substituted or unsubstituted branched acyclic group containing at least 5 carbon atoms at least one of which is a tertiary carbon; and in which Z12 is a cyclic imide. Methods of using these compounds as chiral catalysts for carbenoid reactions and for enantioselective C—H aminations are also described.
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Page/Page column 65

(2008/12/05)

Tannate salt of rasagiline
The subject invention provides rasagiline tannate, compositions and a process for manufacture thereof.
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Page/Page column 1-2

(2008/12/06)

Methods for isolating propargylated aminoindans
Disclosed is a process for isolating from a reaction mixture a salt of a mono-propargylated aminoindan having the structure wherein R1 is H, hydroxyl, alkoxy or wherein Y is O or S; R2 and R3 is each, independently, C1-8 alkyl, C6-12 aryl, C6-12 aralkyl, each optionally halo substituted, or hydrogen; where the reaction mixture further comprises a solvent, a primary aminoindan having the structure wherein R1 is defined as above, and a tertiary aminoindan having the structure the process comprising d) adding an acid to the reaction mixture; e) crystallizing the mono-propargylated aminoindan under conditions suitable for the formation of a crystalline salt of the mono-propargylated aminoindan; and f) recovering the crystalline salt of the mono-propargylated aminoindan, wherein the process is performed without addition of an organic solvent. Also disclosed are the crystalline diastereomeric salts produced by the process and pharmaceutical compositions containing the salts.
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Page/Page column 13

(2008/06/13)

Dirhodium tetracarboxylates derived from adamantylglycine as chiral catalysts for enantioselective C-H aminations
(Chemical Equation Presented) The dirhodium tetracarboxylate, Rh 2(S-TCPTAD)4, derived from adamantylglycine, is an effective chiral catalyst for both inter- and intramolecular C-H aminations.
Reddy, Ravisekhara P.,Davies, Huw M. L.
p. 5013 - 5016
(2007/10/03)

Process for the synthesis of enantiomeric indanylamine derivatives
A process for manufacturing (R)-propynylaminoindans, and alternatively, a process for manufacturing (S)-propynylaminoindans. The chiral propynylaminoindans include alkoxy or alkylcarbamates derivatives. The process comprises transfer or pressure hydrogenation in the presence of an optically active catalyst to reduce 1-indanones. The chiral product, either (S)- or (R)-indanols undergo nucleophilic substitution to produce the named product. In an additional aspect, the invention relates to novel intermediates and compounds, namely, substituted indanones, substituted (S)-indanols and substituted (R)-indanols.
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Page/Page column 8

(2008/06/13)