- 2 - Methyl-pyrazolo [1, 5 - a] pyrimidine - 6 - carboxylic acid derivative and its application
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The invention discloses a 2-methylpyrazolo[1,5-a]pyrimidyl-6-carboxylic acid derivative and application thereof. The 2-methylpyrazolo[1,5-a]pyrimidyl-6-carboxylic acid derivative (I) can be used for synthesizing anagliptin. The compound (I) has high stability, and avoids using expensive reagents and harsh reaction conditions in the anagliptin synthesis process. The compound (I) has the advantages of mild reaction conditions, high reaction yield and stable and controllable quality, is simple to operate, avoids column chromatography, low-temperature reaction and other complex after-treatment processes, greatly lowers the anagliptin preparation cost, and is suitable for industrialized mass preparation. The 2-methylpyrazolo[1,5-a]pyrimidyl-6-carboxylic acid derivative is the compound disclosed as Formula (I).
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- Online Inductive Electrospray Ionization Mass Spectrometry as a Process Analytical Technology Tool to Monitor the Synthetic Route to Anagliptin
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Inductive electrospray ionization (iESI) is an ambient ionization method that is particularly well-suited to online reaction monitoring. It allows the potential of electrospray mass spectrometry (MS) to be realized as a routine process analytical technology (PAT) tool to monitor practical synthetic reactions in real time. In this study, a synthetic route to Anagliptin (target API) was successfully monitored using online iESI-MS. Starting materials not seen by traditional reaction monitoring tools (HPLC-UV/Vis and GC-FID) were observed, as well as water-sensitive reagents and intermediates which cannot easily be followed by other methods. Online tandem mass spectrometry (MS/MS) was used to characterize chemical species in the reaction mixture. Impurities and byproducts were identified, and information on the progress of byproduct formation enabled implementation of strategies to eliminate these byproducts in the course of the reaction. This work demonstrates how iESI-MS can be employed to obtain comprehensive information and solutions to some practical problems that occur in small-molecule synthetic reaction monitoring.
- Yan, Xin,Bain, Ryan M.,Li, Yafeng,Qiu, Ran,Flick, Tawnya G.,Cooks, R. Graham
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p. 940 - 947
(2016/06/13)
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- A PROCESS FOR PREPARATION OF ANAGLIPTIN HYDROCHLORIDE
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The present invention relates to process for preparing dipeptidyl peptidase IV inhibitor Anagliptin free base or its hydrochloride salt by using novel methane sulfonic acid salt of (2S)-1-{[(1-Amino-2-methylpropan-2-yl) amino] acetyl} pyrrolidine-2-carbonitrile (formula IIa). Anagliptin is used for the treatment of diabetes.
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Page/Page column 6
(2016/02/12)
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- A method for synthesizing allah Geleg sandbank (by machine translation)
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The invention relates to a method for preparing anti-II type diabetes drug allah Geleg sandbank method for the synthesis of bulk drug (Anagliptin). The lack of commercial synthetic allah Geleg sandbank solve the technical problems of the method. Synthetic method comprises the following steps : (1) with vinyl ether and trichloro acetyl chloride as the raw material, passes through the three-step reaction to obtain the aldehyde protected intermediates 4 ; The 3-amino-5-methyl pyrazole condensation for dehydrating and gets pyrazolo pyrimidine mother nucleus; Carboxy b ester hydrolysis to obtain 2-methyl-pyrazolo [1,5-a] pyrimidin 6-carboxylic acid 6 ; (2) to L-proline as a raw material, passes through the methyl esterification, ammoniation, acetylation, Carbonitride reaction to obtain the chiral cyano pyrrolizinone intermediate 11 ; Chiral cyano pyrrolizinone intermediate 11 And diamine fragment 12 In alkaline conditions to obtain intermediate affinity substituted 13 ; Finally, intermediate 13 Under the conditions of the hydrochloric acid removal protection Boc base namely obtain cyanopentanoyl Azolylamine intermediate 14 ; (3) 2-methyl-pyrazolo [1,5-a] pyrimidine-6-carboxylic acid 6 The cyano Azolylamine intermediate 14 The condensation conditions to obtain the bulk drug allah Geleg sandbank coupled. (by machine translation)
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- The crystal form and A geleg sandbank pharmaceutical composition (by machine translation)
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This invention relates to the crystalline forms of geleg sandbank A, preparation method and pharmaceutical composition; the crystal form A including the X-ray diffraction pattern at diffraction angles 2 the: 9.860 degrees, 17.435 degrees, 18.622 degrees, 25.211 degrees and the 25.857 degrees display of the diffraction peaks, said powder X-ray diffraction pattern cu is used? The pattern of K α ray obtained; A type that a pharmaceutical composition comprising crystal geleg sandbank, microcrystalline cellulose, crossing linking gathers the Uygur alkone, stearyl fumar sodium, wherein the control of the grain size distribution of the crystal geleg sandbank in D50=45.6-67.6 micron, D90=129.2-159.5 microns, wherein the particle size distribution of the method to measure the laser granulometer. (by machine translation)
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Paragraph 0050; 0051; 0052; 0053; 0058; 0059; 0060
(2016/10/31)
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- AN ADVANTAGEOUS PROCESS FOR PREPARING ANAGLIPTIN AND ITS NOVEL CRYSTALLINE FORM-H
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The present invention discloses the process for preparation of Anagliptin and its novel crystalline form-H.
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Page/Page column 16
(2016/12/22)
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- Compound 1 - (diphenyl methylene) amino-2-amino-2-methyl propane and its preparation method and application
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The invention relates to a new compound 1-(diphenyl methylene) amino-2-amino-2-methylmethane, a preparation method and application thereof in Anagliptin synthesis. 1-(diphenyl methylene) amino-2-amino-2-methylmethane is a (I) compound; the Formula is a key intermediate in the Anagliptin synthesis; the intermediate is stable and easy to get, plays a vital role in synthesizing the final target compound; moreover, the method is simple in technical flow process, higher in yielding and applicable to large-scale production.
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Paragraph 0123-0125
(2017/04/11)
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- CRYSTAL OF N-[2-(AMINO)-2-METHYLPROPYL]-2-METHYLPYRAZOLO[1,5-A]PYRIMIDINE-6-CARBOXAMIDE
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An object is to provide a crystal of anagliptin, which has a high purity and is excellent in stability, low in hygroscopicity, and has a characteristic of easily dissolving into water, and a method for producing the crystal. An anagliptin crystal showing
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Paragraph 0042; 0043; 0044; 0045; 0046; 0047; 0048; 0049
(2015/09/23)
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- PROCESS FOR THE PREPARATION OF ANAGLIPTIN OR ITS SALTS
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The present invention direct to a novel process for the preparation of Anagliptin or its pharmaceutically acceptable salts and intermediates. In the particular aspect, present invention provides an industrially advantageous process for the preparation of Anagliptin.
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Page/Page column 8; 9
(2015/11/17)
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- A PROCESS FOR THE PREPARATION OF ANAGLIPTIN AND ITS INTERMEDIATES THEREOF
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The present invention relates to an improved process for the preparation of Anagliptin, intermediates thereof, or pharmaceutically acceptable thereof. The present invention also direct to another short process for the preparation of Anagliptin. The present invention also specifically provides an improved process for the purification of intermediate of Anagliptin. Further, the present invention relates to a polymorph of Anagliptin or a pharmaceutically acceptable salt thereof and a method for the preparation thereof.
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- COMPOUND INHIBITING DIPEPTIDYL PEPTIDASE IV
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The invention aims to provide a dipeptidyl peptidase IV inhibitor which is satisfactory in respect of activity, stability and safety and has an excellent action as a pharmaceutical agent. The invention is directed to a compound represented by the following general formula or a pharmaceutically acceptable salt thereof: wherein R1 and R2 each represents hydrogen, an optionally substituted C1-6 alkyl group, or -COOR5 whereupon R5 represents hydrogen or an optionally substituted C1-6 alkyl group, or R1 and R2, together with a carbon atom to which they are bound, represent a 3- to 6-membered cycloalkyl group, R3 represents hydrogen or an optionally substituted C6-10 aryl group, R4 represents a hydrogen or a cyano group, D represents -CONR6-, -CO- or -NR6CO-, R6 represents hydrogen or an optionally substituted C1-6 alkyl group, E represents -(CH2)m- whereupon m is an integer of 1 to 3, -CH2OCH2-, or -SCH2-, n is an integer of 0 to 3, and A represents an optionally substituted bicyclic heterocyclic group or bicyclic hydrocarbon group.
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Page/Page column 35
(2010/02/14)
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