739366-20-2

Usage

Uses

Used in Pharmaceutical Industry:
Anagliptin is used as an antidiabetic drug for the treatment of Type 2 diabetes mellitus (T2DM). It helps in controlling blood sugar levels by inhibiting the DPP-4 enzyme, which in turn increases the levels of GLP-1, leading to increased insulin secretion and decreased glucagon secretion.
Used in Cardiovascular Applications:
Anagliptin is used as an anti-atherosclerotic agent to suppress the proliferation of vascular smooth muscles and monocyte inflammatory reaction. It helps in attenuating atherosclerosis in male apolipoprotein E-deficient mice, which can potentially contribute to the prevention and treatment of cardiovascular diseases associated with diabetes.

Originator

Sanwa Kagaku Kenkyusho (Japan)

Clinical Use

Anagliptin, which is marketed as Beskoa or Suiny, is a dipeptidyl peptidase–IV (DPP-4) inhibitor which was approved in September 2012 and launched in November 2012 in Japan for the treatment of Type II diabetes. The drug was co-developed by three Japanese companies; Kowa, Sanwa Kagaku and JW pharmaceutical. Anagliptin, which is more selective against several recombinant human proteases by comparison to sitagliptin and vildagliptin, has more than 10,000-fold selectivity over the structurally homologous DPP-8 and DPP-9 enzymes.

Synthesis

The most likely process-scale synthesis has been published and is depicted in Scheme 3.24 Commercially available (S)-1-(2-chloroacetyl)-pyrrolidine-2-carbonitrile (12) was alkylated with t-butyl (2-amino-2-methyl-1-propyl)carbamate (13), giving rise to (S)-t-butyl (2-((2-(2-cyanopyrrolidin-1-yl)-2- oxoethyl)amino)-2-methylpropyl)carbamate (14). This Boc-protected system was subsequently treated with strong acid to give the ethylene diamine derivative 15 in 96% yield. Activation of 15 with CDI followed by coupling with commercially available 2-methylpyrazolo[1,5-a] pyrimidine-6-carboxylic acid (16) gave anagliptin (III) in 90% yield.

Upstream product

• 739364-95-5 2-methylpyrazolo[1,5-a] pyrimidine-6-carboxylic acid 
• 739365-95-8 tert-butyl N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]carbamate 
• 207557-35-5 (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile 
• 794460-89-2 (S)-1-(2-((1-amino-2-methylpropan-2-yl)amino)acetyl)pyrrolidine-2-carbonitrile 
• 530-62-1 1,1'-carbonyldiimidazole 
• 565452-98-4 1-chloroacetyl-2-cyano-(R)-pyrrolidine 
• 214398-99-9 (S)-1-(2-chloroacetyl) pyrrolidine-2-carboxamide 
• 7531-52-4 L-prolinamide 
• 147-85-3 L-proline 
• 1263061-14-8 2-methyl-pyrazolo[1,5-a]pyrimidine-6-carboxylic acid ethyl ester 

Relevant academic research and scientific papers

2 - Methyl-pyrazolo [1, 5 - a] pyrimidine - 6 - carboxylic acid derivative and its application

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).

AN ADVANTAGEOUS PROCESS FOR PREPARING ANAGLIPTIN AND ITS NOVEL CRYSTALLINE FORM-H

The present invention discloses the process for preparation of Anagliptin and its novel crystalline form-H.

Compound 1 - (diphenyl methylene) amino-2-amino-2-methyl propane and its preparation method and application

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.

A method for synthesizing allah Geleg sandbank (by machine translation)

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)

Online Inductive Electrospray Ionization Mass Spectrometry as a Process Analytical Technology Tool to Monitor the Synthetic Route to Anagliptin

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.

A PROCESS FOR PREPARATION OF ANAGLIPTIN HYDROCHLORIDE

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.

The crystal form and A geleg sandbank pharmaceutical composition (by machine translation)

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)

CRYSTAL OF N-[2-(AMINO)-2-METHYLPROPYL]-2-METHYLPYRAZOLO[1,5-A]PYRIMIDINE-6-CARBOXAMIDE

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

PROCESS FOR THE PREPARATION OF ANAGLIPTIN OR ITS SALTS

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.

A PROCESS FOR THE PREPARATION OF ANAGLIPTIN AND ITS INTERMEDIATES THEREOF

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.