Category: 1220910-89-3

With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.1220910-89-3, name is Benzyl (3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)carbamate, molecular formula is C21H17FN6O2, molecular weight is 404.4, as common compound, the synthetic route is as follows.Recommanded Product: Benzyl (3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)carbamate

A 5-L, three-neck, round-bottom flask was equipped with an overhead stirrer, a thermocouple, a 500-mL addition funnel and a nitrogen-inlet adapter. The flask was dried with a heat gun under a flow of nitrogen to an internal temperature of 60C. The flask was charged with intermediate 7 (110.0 g, 0.272 mol, AMRI lot No. DUG-AF-202Q)) and anhydrous THF (2.2 L, 20 vol). The slurry was stirred and a light green solution formed. The addition funnel was charged with 1.0 M lithium hexamethyldisilazide (299 mL, 0.286 mol, 1.05 eq.). The LiHMDS solution was added dropwise to the solution of intermediate 7 over approximately 25 minutes. A red solution formed. The solution was stirred one hour at room temperature and then DMPU (34.9 g, 0.272 mol, 1 eq) was added, and the mixture turned to a yellow slurry. The batch was cooled in an ice bath to 5.7C. R-(-)-Glycidyl butyrate (41.25 g, 0.286 mol, 1.05 eq) was then added in one portion. The mixture was stirred in the ice bath for 0.5 hour and then was warmed to room temperature and stirred overnight. The reaction formed a tan slurry at this point, and HPLC analysis after 15 hours indicated that there was approximately 87% TR-700, 1.6% intermediate 7, and approximately 7% of the butyrate ester of TR-700. A small amount of sodium methoxide in methanol (11 mL, 0.1 vol) was added, and the batch was stirred for 1 hour to remove the residual ester. The in-process HPLC analysis at this point showed there was approximately 90.7% TR-700 and 0.2% of the butyrate ester. The reaction was quenched by the addition of 10% w/w ammonium chloride solution (1.1 L, 10 vol). A modest exothermic event from 22C to 25C was observed upon addition of the ammonium chloride solution. The two-phase mixture was distilled to a pot temperature of 700C (atmospheric pressure) to remove approximately 2.2 L of the THF. This formed a thick slurry which is diluted with water (550 mL, 5 volumes). The slurry was cooled to room temperature (23.6C) and was filtered. The filter cake was washed with water (1.1 L, 10 vol) and methanol (550 mL, 5 vol) to give TR-700 as a white solid. The wet cake was dried overnight in a vacuum oven at 500C to give 89.7 g of TR-700 (89% yield) that was 97.8% (AUC) by HPLC analysis. The TR-700 was further purified by reslurrying in 2.7 L (30 vol) of 4: 1 methanol/water at 700C, cooling to 230C, filtering and washing with methanol (180 ml). This removed some of the over-alkylated product that is observed. The purified TR- 700 was recovered in 96% yield (85% overall yield), and the purity was improved to 98.4% (AUC) by HPLC analysis. The palladium content was 10 ppm.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,1220910-89-3, Benzyl (3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)carbamate, and friends who are interested can also refer to it.

Reference:
Patent; TRIUS THERAPEUTICS; COSTELLO, Carrie, A.; SIMSON, Jaqueline, A.; DUGUID, Robert, J.; PHILLIPSON, Douglas; WO2010/42887; (2010); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.1220910-89-3, name is Benzyl (3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)carbamate, molecular formula is C21H17FN6O2, molecular weight is 404.4, as common compound, the synthetic route is as follows.Recommanded Product: Benzyl (3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)carbamate

A 5-L, three-neck, round-bottom flask was equipped with an overhead stirrer, a thermocouple, a 500-mL addition funnel and a nitrogen-inlet adapter. The flask was dried with a heat gun under a flow of nitrogen to an internal temperature of 60C. The flask was charged with intermediate 7 (110.0 g, 0.272 mol, AMRI lot No. DUG-AF-202Q)) and anhydrous THF (2.2 L, 20 vol). The slurry was stirred and a light green solution formed. The addition funnel was charged with 1.0 M lithium hexamethyldisilazide (299 mL, 0.286 mol, 1.05 eq.). The LiHMDS solution was added dropwise to the solution of intermediate 7 over approximately 25 minutes. A red solution formed. The solution was stirred one hour at room temperature and then DMPU (34.9 g, 0.272 mol, 1 eq) was added, and the mixture turned to a yellow slurry. The batch was cooled in an ice bath to 5.7C. R-(-)-Glycidyl butyrate (41.25 g, 0.286 mol, 1.05 eq) was then added in one portion. The mixture was stirred in the ice bath for 0.5 hour and then was warmed to room temperature and stirred overnight. The reaction formed a tan slurry at this point, and HPLC analysis after 15 hours indicated that there was approximately 87% TR-700, 1.6% intermediate 7, and approximately 7% of the butyrate ester of TR-700. A small amount of sodium methoxide in methanol (11 mL, 0.1 vol) was added, and the batch was stirred for 1 hour to remove the residual ester. The in-process HPLC analysis at this point showed there was approximately 90.7% TR-700 and 0.2% of the butyrate ester. The reaction was quenched by the addition of 10% w/w ammonium chloride solution (1.1 L, 10 vol). A modest exothermic event from 22C to 25C was observed upon addition of the ammonium chloride solution. The two-phase mixture was distilled to a pot temperature of 700C (atmospheric pressure) to remove approximately 2.2 L of the THF. This formed a thick slurry which is diluted with water (550 mL, 5 volumes). The slurry was cooled to room temperature (23.6C) and was filtered. The filter cake was washed with water (1.1 L, 10 vol) and methanol (550 mL, 5 vol) to give TR-700 as a white solid. The wet cake was dried overnight in a vacuum oven at 500C to give 89.7 g of TR-700 (89% yield) that was 97.8% (AUC) by HPLC analysis. The TR-700 was further purified by reslurrying in 2.7 L (30 vol) of 4: 1 methanol/water at 700C, cooling to 230C, filtering and washing with methanol (180 ml). This removed some of the over-alkylated product that is observed. The purified TR- 700 was recovered in 96% yield (85% overall yield), and the purity was improved to 98.4% (AUC) by HPLC analysis. The palladium content was 10 ppm.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,1220910-89-3, Benzyl (3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)carbamate, and friends who are interested can also refer to it.

Reference:
Patent; TRIUS THERAPEUTICS; COSTELLO, Carrie, A.; SIMSON, Jaqueline, A.; DUGUID, Robert, J.; PHILLIPSON, Douglas; WO2010/42887; (2010); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 1220910-89-3 , The common heterocyclic compound, 1220910-89-3, name is Benzyl (3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)carbamate, molecular formula is C21H17FN6O2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.

To the kettle was added tetrahydrofuran (20 L)And benzyl N- [3-fluoro-4- [6- (2-methyl- 2H- tetrazolium- 5 -yl) -3-pyridyl] phenyl] carbamateCompound (II) (1 Kg, 2.47 mol),0 ~ 30 C After mixing,1,3-Dimethyl-3,4,5,6-tetrahydro-2-pyrimidone was added sequentially (DMPU, 0.63 Kg, 4.94 mol, 2 equivalents),Lithium tert-butoxide (0.396 Kg, 4.94 mol, 2 equivalents)Add R-glycidyl butyrate(0.39 Kg, 2.72 mol, 1.1 equivalents)0 ~ 30 C for 15 hours.After the reaction,The reaction was quenched by adding a mass-volume ammonium chloride solution (1 Kg / 10 L)Concentrated under reduced pressure,The residue was added to methanol (10 L)Stirred for 0.5 hours to give suction filtration,The filter cake was washed with methanol,45 ~ 50 C under vacuum to give a white solid(5R) -3- (4- (6- (2-methyl- 2H- tetrazolium- 5-yl) -3-pyridyl) -3- fluorophenyl) -5-hydroxymethyl oxazoline -2-one Compound (III) (0.87 Kg, yield: 95%).

The synthetic route of 1220910-89-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Nanjing You Ke Pharmaceutical Co., Ltd.; Nanjing You Ke Bio-pharmaceutical Co., Ltd.; Nanjing You Ke Bio-pharmaceutical Group Co., Ltd.; Li Shang; Che Xiaoming; Zhao Zanzan; Zhu Suhua; Xue Yuquan; Zhang Feng; (7 pag.)CN106317114; (2017); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 1220910-89-3, Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps,and cheap raw materials. 1220910-89-3, name is Benzyl (3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)carbamate. A new synthetic method of this compound is introduced below.

Under the protection of nitrogen, to a 100 L reactor, 2.60 kg (6.43 mol) of terdazolamide phosphate intermediate II and 50 L of anhydrous tetrahydrofuran were added and stirred to dissolve. 7.07 liters of 1 mol / L lithium hexamethyldisilazide in tetrahydrofuran solution was added dropwise.Stir at 10 15 for 2 hours, add 1,3-dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone (DMPU) 0.83Kg, and lower the temperature to 0 5 . Add R-glycidyl butyrate 0.97Kg. Stir overnight at 10 C to 15 C to obtain a light yellow slurry.A solution of 33 g of sodium methoxide dissolved in 330 mL of methanol was added and stirred for 1 hour. Add ammonium chloride solution with a mass concentration of 10% (the mass concentration means the mass of ammonium chloride as a percentage of the total mass of ammonium chloride water) 17L.The two-phase mixture was concentrated. Water (13 L, 5 volumes) was added to the concentrated slurry, cooled to room temperature, and filtered. The filter cake was slurried with methanol and water (volume ratio 4: 1) (70 L), then filtered, and filtered The cake was rinsed with 12L of methanol and 12L of water, and the wet product was dried in a vacuum (pressure -0.01MPa -0.1MPa) drying oven at 45 C- 55 C for 8 hours 12 hours to obtain the white solid as terdazolamide phosphate intermediate V 2.01Kg, yield 84.4%. HPLC purity: 99.21%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1220910-89-3, its application will become more common.

Reference:
Patent; Shanghai Bozhi Yan Xin Pharmaceutical Co., Ltd.; Chen Jian; Liu Zhenfeng; Ying Shuhuan; (16 pag.)CN110804038; (2020); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 1220910-89-3, Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps,and cheap raw materials. 1220910-89-3, name is Benzyl (3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)carbamate. A new synthetic method of this compound is introduced below.

Under the protection of nitrogen, to a 100 L reactor, 2.60 kg (6.43 mol) of terdazolamide phosphate intermediate II and 50 L of anhydrous tetrahydrofuran were added and stirred to dissolve. 7.07 liters of 1 mol / L lithium hexamethyldisilazide in tetrahydrofuran solution was added dropwise.Stir at 10 15 for 2 hours, add 1,3-dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone (DMPU) 0.83Kg, and lower the temperature to 0 5 . Add R-glycidyl butyrate 0.97Kg. Stir overnight at 10 C to 15 C to obtain a light yellow slurry.A solution of 33 g of sodium methoxide dissolved in 330 mL of methanol was added and stirred for 1 hour. Add ammonium chloride solution with a mass concentration of 10% (the mass concentration means the mass of ammonium chloride as a percentage of the total mass of ammonium chloride water) 17L.The two-phase mixture was concentrated. Water (13 L, 5 volumes) was added to the concentrated slurry, cooled to room temperature, and filtered. The filter cake was slurried with methanol and water (volume ratio 4: 1) (70 L), then filtered, and filtered The cake was rinsed with 12L of methanol and 12L of water, and the wet product was dried in a vacuum (pressure -0.01MPa -0.1MPa) drying oven at 45 C- 55 C for 8 hours 12 hours to obtain the white solid as terdazolamide phosphate intermediate V 2.01Kg, yield 84.4%. HPLC purity: 99.21%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1220910-89-3, its application will become more common.

Reference:
Patent; Shanghai Bozhi Yan Xin Pharmaceutical Co., Ltd.; Chen Jian; Liu Zhenfeng; Ying Shuhuan; (16 pag.)CN110804038; (2020); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 1220910-89-3, In the chemical reaction process,reaction time,type of solvent,can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product.An updated downstream synthesis route of 1220910-89-3 as follows.

In a 1L three-necked bottle, 50 g of a compound of Formula X3, 400 ml of tetrahydrofuran and 400 ml of acetonitrile were added.Nitrogen gas, temperature 25C, solids insolubleThen, 9.9 g of lithium tert-butoxide and 13.9 g of potassium tert-butoxide were added, and the solid matter dissolved.The reaction solution changed from colorless to yellow,After stirring for 2 hours, the reaction solution was added dropwiseR-(-)-glycidol butyric acid and compound of formula R 19.7 g,After completion of the addition, the reaction was incubated for 3 hours, and the sample was subjected to a TLC (developing solvent: chloroform/methanol = 10/1). After the spot of the compound of Formula X3 disappeared, the sample was dropped.Add dilute hydrochloric acid prepared from concentrated hydrochloric acid and water, adjust the pH to 8, fully stir for 30 minutes, the water bath temperature is 35C to 55C, and the vacuum degree -0.07MPa to -0.1MPa is concentrated under reduced pressure to stop flow.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1220910-89-3, its application will become more common.

Reference:
Patent; Chongqing Huabang Shengkai Pharmaceutical Co., Ltd.; Liu Shuang; Zou Changzhong; Luo Lian; (8 pag.)CN107722056; (2018); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem