- Improved preparation method of rasagiline racemic intermediate
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The invention discloses an improved preparation method of a rasagiline racemic intermediate, belongs to the technical field of medicinal chemistry, and particularly relates to an improved method for preparing an N-(2-propargyl)-2,3-dihydro-1H-indene-1-amine racemic body. According to the invention, the N-(2-propargyl)-2,3-dihydro-1H-indene-1-amine racemic body is prepared by using 1-indanone and propargylamine as raw materials through a one-pot method in the presence of a dehydrating agent; and the method is simple to operate, high in yield and good in purity, and establishes a good foundationfor subsequent preparation of rasagiline mesylate.
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Paragraph 0049; 0050; 0055; 0056
(2020/02/29)
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- Preparation method of rasagiline mesylate and intermediate thereof
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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; 0080-0085
(2019/01/21)
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- PROCESS FOR THE PREPARATION OF ENATIOMERICALLY PURE 1-AMINOINDAN
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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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- Chemoenzymatic synthesis of rasagiline mesylate using lipases
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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
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- A novel synthesis of rasagiline via a chemoenzymatic dynamic kinetic resolution
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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
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p. 1169 - 1174
(2014/12/10)
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- Process for preparation of Rasagiline and salts thereof
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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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- NEW METHOD FOR THE SYNTHESIS OF RASAGILINE
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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 0031
(2014/02/16)
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- A PROCESS FOR THE PREPARATION OF N-PROPRAGYL 1-AMINO INDANE AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
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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 13
(2013/04/25)
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- RASAGILINE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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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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- A NEW METHOD FOR THE SYNTHESIS OF RASAGILINE
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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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- Process for preparation of rasagiline and salts thereof
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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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- METHOD FOR PRODUCING COMPOUND FOR PREPARATION OF ANTI-PARKINSON'S DISEASE DRUG
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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 4-5
(2011/10/02)
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- PROCESSES FOR THE PREPARATION OF PROPARGYLATED AMINOINDANS OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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The present invention relates to preparation of a compound of formula (I), wherein R1 = H or formula (b) and R2 is C1-C4 alkyl, R3 = H or C1-C4 alkyl comprising: a) reacting an indanone derivative or a salt thereof of formula (II) with the propargyl amine or a salt thereof of formula (III) in the presence of a Lewis acid; and b) subjecting the resultant reaction mixture to reduction
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- POLYMORPHIC FORM OF RASAGILINE MESYLATE
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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 10
(2010/04/03)
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- PREPARATION OF RASAGILINE AND SALTS THEREOF
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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)
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- Crystalline Form of Rasagiline and Process for the Preparation Thereof
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A process for the preparation of (R)—N-propargyl-1-aminoindane, or a salt thereof, comprising reacting 1-indanone with propargylamine, in presence of a mixture of sodium borohydride and acetic acid, to obtain N-propargyl-1-aminoindane; and its conversion into (R)—N-propargyl-1-aminoindane or a salt thereof.
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Page/Page column 4
(2010/03/02)
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- NEW METHOD FOR OBTAINING AN AMINOINDAN MESYLATE DERIVATIVE
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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 4
(2009/12/05)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF AMINES
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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 14
(2009/12/28)
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- RASAGILINE MESYLATE PARTICLES AND PROCESS FOR THE PREPARATION THEREOF
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Provided herein is rasagiline mesylate having a 90 volume-percent of the particles (D90) with a size of about 600 microns to about 1500 microns, and a process for the preparation thereof. Provided also herein are pharmaceutical compositions comprising rasagiline mesylate particles having a particle size which is suitable for homogeneous distribution of the drug substance in a tablet blend, in particular 90 volume-percent of the particles (D90) have a size of about 255 microns to about 1500 microns, and a process the preparation thereof.
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Page/Page column 12
(2009/10/30)
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- PROCESS FOR THE SYNTHESIS OF PROPARGYLATED AMINOINDAN DERIVATIVES
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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 12-13
(2009/07/25)
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- Methods for isolating propargylated aminoindans
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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)
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- Use of R-enantiomer of N-propargyl-1-aminoindan, salts, and compositions thereof
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The subject invention provides R(+)-N-propargyl-1-aminoindan and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions containing same. The subject invention also provides methods of treating a subject afflicted with Parkinson's disease, a memory disorder, dementia, depression, hyperactive syndrome, an affective illness, a neurodegenerative disease, a neurotoxic injury, stroke, brain ischemia, a head trauma injury, a spinal trauma injury, neurotrauma, schizophrenia, an attention deficit disorder, multiple sclerosis, or withdrawal symptoms, using R(+)-N-propargyl-1-aminoindan or the pharmaceutically acceptable salt of the subject invention. The subject invention further provides a method of preventing nerve damage in a subject. Finally, the subject invention provides methods of preparing R(+)-N-propargyl-1-aminoindan, a salt thereof, and racemic N-propargyl-1-aminoindan.
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