WO2015150887A1 - Process for the preparation of anagliptin or its salts - Google Patents
Process for the preparation of anagliptin or its salts Download PDFInfo
- Publication number
- WO2015150887A1 WO2015150887A1 PCT/IB2014/066940 IB2014066940W WO2015150887A1 WO 2015150887 A1 WO2015150887 A1 WO 2015150887A1 IB 2014066940 W IB2014066940 W IB 2014066940W WO 2015150887 A1 WO2015150887 A1 WO 2015150887A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- anagliptin
- formula
- solvent
- pyrimidine
- methylpyrazolo
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Definitions
- the present invention direct to a process for the preparation of Anagliptin or its pharmaceutically acceptable salts and intermediates.
- present invention provides an industrially advantageous process for the preparation of Anagliptin.
- the drug compound having the adopted name "Anagliptin” has chemical name,N-[2-( ⁇ 2- [(2S)-2-Cyanopyrrolidin-l-yl]-2-oxoethyl ⁇ amino)-2-methylpropyl]-2-methylpyrazolo
- the pharmaceutical product Suini® tablets contain Anagliptin as active ingredient.
- Anagliptin is a DPP-4 (dipeptidyl peptidase-4) inhibitor useful for the treatment of diabetes.
- US Patent No. 7,345, 180 describes Anagliptin and process for the preparation thereof.
- the process of US' 180 involves reaction of 2-methylpyrazolo [1, 5-a] pyrimidin-6-yl with (S)-l-(2'-Chloroacetyl) pyrrolidine-2-carbonitrile in presence of potassium carbonate and sodium iodide in acetone for a period of 8 hours at room temperature.
- the present invention provides a economically viable industrial eco-friendly process for the preparation of Anagliptin or its pharmaceutically acceptable salts thereof
- the process includes steps of:
- catalyst includes metal halides like potassium iodide, sodium bromide, sodium iodide and the like.
- suitable organic solvent includes a mixture of one or more halogenated solvent and ethers, where the preferred solvent is a halogenated solvent.
- organic solvent includes halogenated solvent.
- the intermediates and starting materials of the present invention may be used as free bases.
- the process includes steps of:
- the reaction between 2-methylpyrazolo[l,5-a] pyrimidine-6-carboxylic acid and ⁇ , ⁇ '- carbonyldiimidazole may be carried out in an inert atmosphere at a temperature in the range of 20°C to 40°C.
- the solvent may be selected from a suitable organic solvent.
- the suitable organic solvent may be a mixture of one or more halogenated solvent and ethers.
- the halogenated solvent may be selected from dichloromethane, dichloroethane, chloroform, chlorobenzene and the like.
- the ether solvent may be selected from dimethyl ether, diethyl ether, dioxane and the like.
- the obtained 2-methylpyrazolo[l,5-a]pyrimidine-6-carboxylic acid-N,N'-carbonyl diimidazole mixture may be added to 2-methyl- 1 ,2-propane diamine at a temperature range of -10°C to 10°C. After completion of reaction, water may be added and N-(2- amino-2-methylpropyl)2-methylpyrazolo[ 1 ,5-a]pyrimidine-6-carboxamide may be isolated from the reaction mixture.
- l-(2-chloroacetyl)-2S-pyrrolidine carbonitrile may be added to N-(2-amino-2-methylpropyl)2-methylpyrazolo[l,5-a]pyrimidine-6-carboxamide at the temperature in the range of 20°C to 30°C in an organic solvent.
- the organic solvent may be halogenated solvent.
- the halogenated solvent is selected from dichlorome thane, dichloroethane, chloroform, chlorobenzene and the like.
- Anagliptin After completion of reaction, water may be added and crude Anagliptin may be isolated from the organic solvent.
- the isolation process involves the removal of solvent under reduced pressure, plain distillation at atmospheric pressure or addition of anti-solvent in the solution or syrupy mass of Anagliptin.
- the Anti-solvent is the solvents in which the Anagliptin is insoluble or has low solubility and it is sufficient enough to precipitate the Anagliptin.
- the condensation reaction may be conducted in the presence of an organic base, which includes but is not limited to triethylamine, 4-dimethylaminopyridine, diisopropylamine and the like and in the presence of a catalyst, which includes, but is not limited to sodium iodide, potassium iodide and sodium bromide.
- an organic base which includes but is not limited to triethylamine, 4-dimethylaminopyridine, diisopropylamine and the like
- a catalyst which includes, but is not limited to sodium iodide, potassium iodide and sodium bromide.
- the crude Anagliptin may be purified using solvents like esters for example isopropyl acetate.
- the crude Anagliptin may be purified by dissolving in isopropyl acetate.
- the purification process involves the dissolution of Anagliptin in isopropyl acetate at the elevated temperature more than 35°C. Further the partial removal of solvent from the solution of Anagliptin. The partial removal includes the solvent quantity which is finally present in the mass is 2-5 times of the weight of Anagliptin.
- the process further includes the cooling of solution or syrupy mass of Anagliptin at the temperature below the 0°C - 20°C for the complete precipitation of the product.
- the purified Anagliptin has purity 99.5% or more when measured by HPLC.
- the present invention may further be illustrated by the following examples which may be provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents may be apparent to those skilled in the art and may be intended within the scope of the present invention.
- Example 1 Process for preparation of N-(2-amino-2-methylpropyl)-2-methyl- pyrazolo [1, 5-a] pyrimidine-6-carboxamide
- N, N'-carbonyldiimidazole (9.6g) was added to a solution of 2-methylpyrazolo [1, 5-a] pyrimidin-6-carboxylic acid (lO.Og) in dichloromethane under nitrogen at 25°C-30°C and stirred the reaction mixture for 1 hour.
- the reaction mixture was added slowly to a solution of 2-methyl- 1 ,2-propanediamine (5.5g) in dichloromethane at 0°C-10°C. The reaction mixture was maintained till completion of reaction. Water was added to the reaction mixture and dichloromethane layer was separated. The combined dichloromethane layers were concentrated to get N-(2-amino-2-methylpropyl)-2-methyl- pyrazolo [l,5-a]pyrimidine-6-carboxamide (8.8g).
- Anagliptin (2g) was dissolved in isopropyl acetate (20ml) at reflux temperature. The clear solution obtained was filtered. Filtrate was put under reduced pressure for the partial removal of isopropyl acetate (15ml). The reaction mixture was cooled to temperature of 5°C -8°C, stirred for an hour and filtered. Solid was washed with isopropyl acetate and dried to get pure Anagliptin.
Abstract
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.
Description
PROCESS FOR THE PREPARATION OF ANAGLIPTIN OR ITS SALTS
Field of Invention
The present invention direct to a 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.
Background of the invention
The drug compound having the adopted name "Anagliptin" has chemical name,N-[2-({2- [(2S)-2-Cyanopyrrolidin-l-yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methylpyrazolo
[1,5-a] pyrimidine-6-carboxamide; and has the structural formula I:
Formula I
The pharmaceutical product Suini® tablets contain Anagliptin as active ingredient. Anagliptin is a DPP-4 (dipeptidyl peptidase-4) inhibitor useful for the treatment of diabetes.
US Patent No. 7,345, 180 describes Anagliptin and process for the preparation thereof. The process of US' 180 involves reaction of 2-methylpyrazolo [1, 5-a] pyrimidin-6-yl with (S)-l-(2'-Chloroacetyl) pyrrolidine-2-carbonitrile in presence of potassium carbonate and sodium iodide in acetone for a period of 8 hours at room temperature.
Kato Noriyasu et al in Bioorganic and Medicinal Chemistry 19(23), 2011, 7221-7227 reported synthesis of Anagliptin hydrochloride. The process involves selective protection
of 2-amino-2-methylpropylamine with di-tert-butyl dicarbonate and condensation with (S)-l-(2-chloroacetyl) pyrrolidine-2-carbonitrile. After deprotection of the BOC group, the amino pyrrolidine is condensed with pyrimidine acid in tetrahydrofuran in presence of N, N-carbonyldiimidazole to give Anagliptin which is converted to Anagliptin hydrochloride using hydrochloric acid in 1 , 4-dioxan.
Other reported processes in WO 2011/075699, WO 2006/060122, WO 2009/047240, WO 2011/026241, and WO 2011/006074, JP 2010/064982, Freire Felix et. al., in Journal of the American Chemical Society, 131(23), 7970-7972; 2009, Isfort, Christian Schulze et al., in Chemistry - A European Journal, 13(8), 2344-2357; 2007, disclosed the compound Boc-aminopyrrolidine , which is referred as formula VIII in the present application.. Moreover the reported processes suffers one or the other problems like formation of impurities, longer duration of reaction, use of number of solvents, use of bases, etc and made the process expensive.
The reported processes for preparing the compound of formula VIII, Boc- aminolyrollidine by, Kato Noriyasu et al., in Bioorganic & Medicinal Chemistry, 19(23), 7221-7227; 2011 and US 7,345, 180, involves condensation using potassium carbonate in the acetone. However, the prior art process has disadvantages including formation of dimer of pyrrolidine of Formula A more than 10%.
The reported processes involve protection and deprotection which are tedious and increases the steps and the cost of process, making it lengthy and cumbersome. Hence there is a need to develop a simple and short process which would be cost effective and commercially viable.
The reported processes also suffer from disadvantages such as use of number of multiple reagents, solvents, low yield and purity of the key intermediate, e.g. Boc- aminopyrrolidine. To make intermediate with lower impurity and removal of carry forward impurities require tedious purification process at final API or its intermediate stages.
The inventors while developing the process of Anagliptin come across the process which involves the reaction of 2-methylpyrazolo[l,5-a] pyrimidine-6-carboxylic acid with 2- methyl- 1 ,2-propane diamine, which reacts further with l-(2-chloroacetyl)-2S-pyrrolidine carbonitrile to get Anagliptin or its salts in a very simple steps.
Summary of the Invention
The present invention provides a economically viable industrial eco-friendly process for the preparation of Anagliptin or its pharmaceutically acceptable salts thereof
In one of the aspect of the present invention provides a process for the preparation of Anagliptin or pharmaceutically acceptable salts thereof,
Formula I
the process includes steps of:
a) treating 2-methyl-l,2-propane diamine of formula II, with
Formula II
2-methylpyrazolo[l,5-a] pyrimidine- -carbox lic acid and
Formula III
Ν,Ν'-carbonyldiimadazole in presence of suitable organic solvent to obtain N-(2- amino-2-methylpropyl)2-methylpyrazolo[ 1 ,5-a]pyrimidine-6-carboxamide of formula IV
Formula IV
b) condensing N-(2-amino-2-methylpropyl)2-methylpyrazolo[l,5-a] pyrimidine-6- carboxamide of formula IV with l-(2-chloroacetyl)-2S-pyrrolidine carbonitrile of formula V,
Formula V
in presence of base and a catalyst in solvent,
c) isolating Anagliptin or salts thereof from the reaction mixture.
Description of the Invention
For purposes of the present invention, the following terms are defined below.
In general, the term "catalyst" includes metal halides like potassium iodide, sodium bromide, sodium iodide and the like.
The term "suitable organic solvent" includes a mixture of one or more halogenated solvent and ethers, where the preferred solvent is a halogenated solvent.
The term "organic solvent" includes halogenated solvent.
The intermediates and starting materials of the present invention may be used as free bases.
In an aspect of the present invention is to provide a process for the preparation of Anagliptin or pharmaceutically acceptable salts thereof,
Formula I
the process includes steps of:
a) treating 2-methyl-l,2-propane diamine of formula II, with
Formula II
2-methylpyrazolo[l,5-a] pyrimidine-6-carboxylic acid and
Formula III
Ν,Ν'-carbonyldiimadazole in presence of suitable organic solvent to obtain N-(2- amino-2-methylpropyl)2-methylpyrazolo[ 1 ,5-a]pyrimidine-6-carboxamide of formula IV
Formula IV
b) condensing N-(2-amino-2-methylpropyl)2-methylpyrazolo[l,5-a] pyrimidine-6- carboxamide of formula IV with l-(2-chloroacetyl)-2S-pyrrolidine carbonitrile of formula V,
Formula V
in presence of base and a catalyst in solvent,
c) isolating Anagliptin or salts thereof from the reaction mixture.
The reaction between 2-methylpyrazolo[l,5-a] pyrimidine-6-carboxylic acid and Ν,Ν'- carbonyldiimidazole may be carried out in an inert atmosphere at a temperature in the range of 20°C to 40°C. The solvent may be selected from a suitable organic solvent. The suitable organic solvent may be a mixture of one or more halogenated solvent and ethers. The halogenated solvent may be selected from dichloromethane, dichloroethane, chloroform, chlorobenzene and the like. Further, the ether solvent may be selected from dimethyl ether, diethyl ether, dioxane and the like.
The obtained 2-methylpyrazolo[l,5-a]pyrimidine-6-carboxylic acid-N,N'-carbonyl diimidazole mixture may be added to 2-methyl- 1 ,2-propane diamine at a temperature range of -10°C to 10°C. After completion of reaction, water may be added and N-(2- amino-2-methylpropyl)2-methylpyrazolo[ 1 ,5-a]pyrimidine-6-carboxamide may be isolated from the reaction mixture.
In the condensation reaction, l-(2-chloroacetyl)-2S-pyrrolidine carbonitrile may be added to N-(2-amino-2-methylpropyl)2-methylpyrazolo[l,5-a]pyrimidine-6-carboxamide at the temperature in the range of 20°C to 30°C in an organic solvent. The organic solvent may be halogenated solvent. The halogenated solvent is selected from dichlorome thane, dichloroethane, chloroform, chlorobenzene and the like.
After completion of reaction, water may be added and crude Anagliptin may be isolated from the organic solvent. The isolation process involves the removal of solvent under reduced pressure, plain distillation at atmospheric pressure or addition of anti-solvent in the solution or syrupy mass of Anagliptin. The Anti-solvent is the solvents in which the Anagliptin is insoluble or has low solubility and it is sufficient enough to precipitate the Anagliptin.
The condensation reaction may be conducted in the presence of an organic base, which includes but is not limited to triethylamine, 4-dimethylaminopyridine, diisopropylamine and the like and in the presence of a catalyst, which includes, but is not limited to sodium iodide, potassium iodide and sodium bromide.
The crude Anagliptin may be purified using solvents like esters for example isopropyl acetate.
In another aspect the crude Anagliptin may be purified by dissolving in isopropyl acetate. The purification process involves the dissolution of Anagliptin in isopropyl acetate at the elevated temperature more than 35°C. Further the partial removal of solvent from the solution of Anagliptin. The partial removal includes the solvent quantity which is finally present in the mass is 2-5 times of the weight of Anagliptin. The process further includes the cooling of solution or syrupy mass of Anagliptin at the temperature below the 0°C - 20°C for the complete precipitation of the product.
In another embodiment of the invention, the purified Anagliptin has purity 99.5% or more when measured by HPLC.
The present invention may further be illustrated by the following examples which may be provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents may be apparent to those skilled in the art and may be intended within the scope of the present invention.
EXAMPLES
Example 1: Process for preparation of N-(2-amino-2-methylpropyl)-2-methyl- pyrazolo [1, 5-a] pyrimidine-6-carboxamide
N, N'-carbonyldiimidazole (9.6g) was added to a solution of 2-methylpyrazolo [1, 5-a] pyrimidin-6-carboxylic acid (lO.Og) in dichloromethane under nitrogen at 25°C-30°C and stirred the reaction mixture for 1 hour. The reaction mixture was added slowly to a solution of 2-methyl- 1 ,2-propanediamine (5.5g) in dichloromethane at 0°C-10°C. The reaction mixture was maintained till completion of reaction. Water was added to the reaction mixture and dichloromethane layer was separated. The combined dichloromethane layers were concentrated to get N-(2-amino-2-methylpropyl)-2-methyl- pyrazolo [l,5-a]pyrimidine-6-carboxamide (8.8g).
Example-2: Preparation of Anagliptin
Diisopropylamine (3.8g), sodium iodide (5.2g) and (S)-l-(2'-chloroacetyl) pyrrolidine-2- carbonitrile (6.0g) was added to solution of N-(2-amino-2-methylpropyl)-2-methyl- pyrazolo [1,5-a] pyrimidine-6-carboxamide (8.0g) in dichloromethane. The reaction mixture was heated to temperature of 35°C-40°C and maintained till completion of reaction. Water was added and the dichloromethane layer was separated and concentrated to get crude Anagliptin. The crude Anagliptin was purified using Isopropyl acetate to get pure Anagliptin.
HPLC purity : 99.6%.
Yield : 3.0 g.
Example-3: Purification of Anagliptin
The Anagliptin (2g) was dissolved in isopropyl acetate (20ml) at reflux temperature. The clear solution obtained was filtered. Filtrate was put under reduced pressure for the partial removal of isopropyl acetate (15ml). The reaction mixture was cooled to temperature of 5°C -8°C, stirred for an hour and filtered. Solid was washed with isopropyl acetate and dried to get pure Anagliptin.
Yield: 1.8 gm
HPLC purity: 99.7%
Claims
Claims:
A process for the preparation of Anagliptin or pharmaceutically acceptable salts thereof,
Formula I
the process comprising of:
a) treating 2-methyl-l,2-propane diamine of formula II, with
Formula II
2-methylpyrazolo[l,5-a] pyrimidine- -carboxylic acid and
Formula III
Ν,Ν'-carbonyldiimadazole in presence of suitable organic solvent to obtain N-(2- amino-2-methylpropyl)2-methylpyrazolo[ 1 ,5-a]pyrimidine-6-carboxamide of formula IV
b) condensing N-(2-amino-2-methylpropyl)2-methylpyrazolo[l,5-a] pyrimidine-6- carboxamide of formula IV with l-(2-chloroacetyl)-2S-pyrrolidine carbonitrile of formula V,
Formula V
in presence of base and a catalyst in solvent,
c) isolating Anagliptin or salts thereof from the reaction mixture.
2. The process of claim 1, wherein the suitable organic solvent in step (a) is a mixture of halogenated solvent and ether.
3. The process of claim 1, wherein the suitable solvent in step (a) is dichloromethane.
4. The process of claim 1, wherein the solvent in step (b) is dichloromethane.
5. The process of claim 1, wherein the base in step (b) is diisopropylamine.
6. The process of claim 1, wherein the catalyst in step (b) is sodium iodide.
7. The process of claim 1, wherein the condensation step (a) is carried at temperature range in between 0°C - 10°C.
8. The process of claim 1, wherein the condensation step (b) is carried at temperature range in between 35°C - 40°C.
9. A purification process, wherein the HPLC purity of Anagliptin is 99.5% or more when measured by HPLC is obtained the process comprising treating Anagliptin with isopropyl acetate.
10. The process of claim 9, wherein Anagliptin is further converted in to its pharmaceutically acceptable salts thereof.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1191/MUM/2014 | 2014-03-29 | ||
| IN1191MU2014 IN2014MU01191A (en) | 2014-03-29 | 2014-12-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2015150887A1 true WO2015150887A1 (en) | 2015-10-08 |
Family
ID=54239455
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB2014/066940 WO2015150887A1 (en) | 2014-03-29 | 2014-12-16 | Process for the preparation of anagliptin or its salts |
Country Status (2)
| Country | Link |
|---|---|
| IN (1) | IN2014MU01191A (en) |
| WO (1) | WO2015150887A1 (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006060122A2 (en) | 2004-11-30 | 2006-06-08 | Artesian Therapeutics, Inc. | Cardiotonic compounds with inhibitory activity against beta-adrenergic receptors and phosphodiesterase |
| US7345180B2 (en) | 2003-01-31 | 2008-03-18 | Sanwa Kagaku Kenkyusho Co., Ltd. | Compound inhibiting dipeptidyl peptidase IV |
| WO2009047240A1 (en) | 2007-10-09 | 2009-04-16 | Smithkline Beecham Corporation | Indole derivatives useful as ppar activators |
| JP2010064982A (en) | 2008-09-10 | 2010-03-25 | Dainippon Sumitomo Pharma Co Ltd | Alkylamino derivative |
| WO2011006074A1 (en) | 2009-07-09 | 2011-01-13 | Array Biopharma Inc. | SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS TRK KINASE INHIBITORS |
| WO2011026241A1 (en) | 2009-09-04 | 2011-03-10 | Zalicus Pharmaceuticals Ltd. | Substituted heterocyclic derivatives for the treatment of pain and epilepsy |
| WO2011075699A2 (en) | 2009-12-18 | 2011-06-23 | Sunovion Pharmaceuticals Inc. | Compounds for treating disorders mediated by metabotropic glutamate receptor 5, and methods of use thereof |
| WO2014034626A1 (en) * | 2012-08-28 | 2014-03-06 | 株式会社 三和化学研究所 | CRYSTAL OF N-[2-({2-[(2S)-2-CYANOPYRROLIDIN-1-YL]-2- OXOETHYL}AMINO)-2-METHYLPROPYL]-2-METHYLPYRAZOLO[1,5-a]PYRIMIDINE-6-CARBOXAMIDE |
-
2014
- 2014-12-16 IN IN1191MU2014 patent/IN2014MU01191A/en unknown
- 2014-12-16 WO PCT/IB2014/066940 patent/WO2015150887A1/en active Application Filing
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7345180B2 (en) | 2003-01-31 | 2008-03-18 | Sanwa Kagaku Kenkyusho Co., Ltd. | Compound inhibiting dipeptidyl peptidase IV |
| WO2006060122A2 (en) | 2004-11-30 | 2006-06-08 | Artesian Therapeutics, Inc. | Cardiotonic compounds with inhibitory activity against beta-adrenergic receptors and phosphodiesterase |
| WO2009047240A1 (en) | 2007-10-09 | 2009-04-16 | Smithkline Beecham Corporation | Indole derivatives useful as ppar activators |
| JP2010064982A (en) | 2008-09-10 | 2010-03-25 | Dainippon Sumitomo Pharma Co Ltd | Alkylamino derivative |
| WO2011006074A1 (en) | 2009-07-09 | 2011-01-13 | Array Biopharma Inc. | SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS TRK KINASE INHIBITORS |
| WO2011026241A1 (en) | 2009-09-04 | 2011-03-10 | Zalicus Pharmaceuticals Ltd. | Substituted heterocyclic derivatives for the treatment of pain and epilepsy |
| WO2011075699A2 (en) | 2009-12-18 | 2011-06-23 | Sunovion Pharmaceuticals Inc. | Compounds for treating disorders mediated by metabotropic glutamate receptor 5, and methods of use thereof |
| WO2014034626A1 (en) * | 2012-08-28 | 2014-03-06 | 株式会社 三和化学研究所 | CRYSTAL OF N-[2-({2-[(2S)-2-CYANOPYRROLIDIN-1-YL]-2- OXOETHYL}AMINO)-2-METHYLPROPYL]-2-METHYLPYRAZOLO[1,5-a]PYRIMIDINE-6-CARBOXAMIDE |
Non-Patent Citations (5)
| Title |
|---|
| FREIRE FELIX, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 131, no. 23, 2009, pages 7970 - 7972 |
| ISFORT ET AL., CHRISTIAN SCHULZE ET AL., IN CHEMISTRY - A EUROPEAN JOURNAL, vol. 13, no. 8, 2007, pages 2344 - 2357 |
| KATO NORIYASU ET AL., BIOORGANIC & MEDICINAL CHEMISTRY, vol. 19, no. 23, 2011, pages 7221 - 7227 |
| KATO NORIYASU ET AL., BIOORGANIC AND MEDICINAL CHEMISTRY, vol. 19, no. 23, 2011, pages 7221 - 7227 |
| NORIYASU KATO ET AL: "Discovery and pharmacological characterization of-[2-({2-[(2)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methylpyrazolo[1,5-]pyrimidine-6-carboxamide hydrochloride (anagliptin hydrochloride salt) as a potent and selective DPP-IV inhibitor", BIOORGANIC & MEDICINAL CHEMISTRY, PERGAMON, GB, vol. 19, no. 23, 23 September 2011 (2011-09-23), pages 7221 - 7227, XP028104550, ISSN: 0968-0896, [retrieved on 20111002], DOI: 10.1016/J.BMC.2011.09.043 * |
Also Published As
| Publication number | Publication date |
|---|---|
| IN2014MU01191A (en) | 2015-10-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11739057B2 (en) | Polymorphic forms of Belinostat and processes for preparation thereof | |
| JP2006515829A5 (en) | ||
| WO2012025944A2 (en) | Sitagliptin, salts and polymorphs thereof | |
| US8912325B2 (en) | Process for preparation of imatinib and its mesylate salt | |
| WO2014125506A2 (en) | A process for the preparation of ivacaftor and its intermediates | |
| US10266507B2 (en) | Process for the preparation of ranolazine | |
| EP3344608B1 (en) | A process for the preparation of xylene linked cyclam compounds | |
| US8598370B2 (en) | Process for producing threo-3-(3,4-dihydroxyphenyl)-L-serine | |
| EP1758867B1 (en) | Process for preparing oxcarbazepine | |
| US8952148B2 (en) | Process for the preparation of taurolidine and its intermediates thereof | |
| WO2015150887A1 (en) | Process for the preparation of anagliptin or its salts | |
| US8093384B2 (en) | Processes for the preparation of alfuzosin | |
| WO2001021592A1 (en) | Processes for the preparation of 4(5)-amino-5(4)-carboxamidoimidazoles and intermediates thereof | |
| US9630909B2 (en) | Process for the preparation of nepafenac | |
| EP2999693B1 (en) | A process for preparing ivabradine | |
| WO2006090265A2 (en) | Processes for the preparation of levetiracetam, its intermediate and the use of levetiracetam in pharmaceutical compositions | |
| WO2016027077A1 (en) | Processes for the preparation of dabigatran etexilate and intermediates thereof | |
| WO2019008595A1 (en) | Process for the preparation of 1-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-(1- methylpiperidin-4-yl)urea and salts thereof | |
| EP3679030B1 (en) | A process for preparation of triaminopyrimidine compound and intermediates thereof | |
| CN113773323B (en) | Preparation method of 3R-amino substituted butyramide derivative | |
| CN111247127B (en) | Process for the production of intermediate compounds for the synthesis of medicaments | |
| US10906866B2 (en) | Process for the preparation of phenoxybenzamine | |
| TW200412946A (en) | Synthesis of pyrrolidine derivatives and their salts | |
| US20100174073A1 (en) | Process for the preparation of alfuzosin and salts thereof | |
| US20240124393A1 (en) | Process and intermediates for preparation of omaveloxolone and salts thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 14833387 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase | ||
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 14833387 Country of ref document: EP Kind code of ref document: A1 |