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Type | HazMat fee for 500 gram (Estimated) |
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Structure of 1020157-01-0
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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Search for reports by entering the product batch number.
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CAS No. : | 1020157-01-0 |
Formula : | C48H44N6O6 |
M.W : | 800.90 |
SMILES Code : | O=C1OC(C)=C(COC(C2=C(C(C)(C)O)N=C(CCC)N2CC3=CC=C(C4=CC=CC=C4C5=NN(C(C6=CC=CC=C6)(C7=CC=CC=C7)C8=CC=CC=C8)N=N5)C=C3)=O)O1 |
MDL No. : | MFCD20272387 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H228-H315-H319 |
Precautionary Statements: | P240-P210-P241-P264-P280-P302+P352-P370+P378-P337+P313-P305+P351+P338-P362+P364-P332+P313 |
Class: | 4.1 |
UN#: | 1325 |
Packing Group: | Ⅱ |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sulfuric acid; In water; acetone; at 50 - 55℃; for 2h; | A solution of 96% H2SO4 (13.2 mL, 248.07 mmol, 3.0 eq) in H2O (264 mL) was added to asuspension of the ester 6 (66.23 g, 82.69 mmol, 1.0 eq) in Me2CO (132 mL). After heating at 50-55 Cfor 2 h, TLC analysis (50% AcOEt/hexanes, Rf = 0.36 for 6) indicated the disappearance of the startingmaterial. The hot solution was diluted with H2O (264 mL) and then cooled to 10 C in an ice-waterbath. Precipitated triphenylmethanol was removed by filtration and washed with H2O (4 × 25 mL).The combined filtrate and washings were diluted with CH2Cl2 (200 mL) and then, while stirring, A solution of 96% H2SO4 (13.2 mL, 248.07 mmol, 3.0 eq) in H2O (264 mL) was added to asuspension of the ester 6 (66.23 g, 82.69 mmol, 1.0 eq) in Me2CO (132 mL). After heating at 50-55 Cfor 2 h, TLC analysis (50% AcOEt/hexanes, Rf = 0.36 for 6) indicated the disappearance of the startingmaterial. The hot solution was diluted with H2O (264 mL) and then cooled to 10 C in an ice-waterbath. Precipitated triphenylmethanol was removed by filtration and washed with H2O (4 × 25 mL).The combined filtrate and washings were diluted with CH2Cl2 (200 mL) and then, while stirring, |
With acetic acid; In water; at 55 - 60℃; for 2 - 3h;Product distribution / selectivity; | METHOD 1 : 50 g of (5-Methyl-2-oxo-1,3-dioxolen-4-yl) methyl-4 (1 -hydroxy -1- methylethyl) 2-propyl1-{phenyl}4-[2-(trityltetrazol-5-yl)phenyl]methylimidazol-5- carboxylate of Formula VII was taken into 1500 ml of 40% aqueous acetic acid and heated at 55 to 60 C for 3 hours. The reaction mass was cooled to 28 C and diluted with 750 ml of water. The precipitated solid was removed by filtration and the filtrate was extracted with 1250 ml methylene chloride. The organic layer was washed with a mixture of 5% aqueous sodium bicarbonate solution (450 ml) and aqueous 5% sodium chloride solution (450 ml) three times. The solvent was distilled from the organic layer under a pressure of 300-400 mm Hg and the residue was co-distilled with 50 ml toluene. The crude product was finally recrystallized from acetone to get 26.5 g of the title compound. METHOD 3: 110 g of (5-Methyl-2-oxo-1 , 3-dioxolen-4~yl)-methyl-4(1 -hydroxy 1- methylethyl)2-propyl1- {phenyl} 4-[2-(trityltetrazol-5-y I) phenyl] methylimidazol-5- EPO <DP n="24"/>carboxylate of Formula VII was added to 2200 ml of 50% aqueous acetic acid, and the reaction mass was heated at 60 C for 2 hours. After completion of reaction, the reaction mass was diluted with 1100 ml of water and cooled to -5 C. The precipitated solid was removed by filtration and the filtrate was extracted with 3300 ml of methylene chloride. The organic layer was washed with 1320 ml of aqueous 5% sodium chloride solution three times. After concentration of solvent, the residue was co-distilled with 660 ml toluene three times. The crude product was finally recrystallized from acetonitrile to get 56 g of the title compound. EXAMPLE 9 PREPARATION OF (5-METHYL-2-OXO-1 ,3-DIOXOLEN-4-YL)METHYL 4-(1- HYDROXY-1-METHYLETHYL)-2-PROPYL-1-f4-r2-(TETRAZOL-5-YL)PHENYLl PHENYL1METHYL -IMIDAZOLE-delta-CARBOXYLATE (OLM ESARTAN MEDOXOMIL.FORMULA I). 300 liters of acetic acid was taken into a reactor and 418 liters of water was added to it. The reaction mass was stirred for 10 minutes and 25 kg of (5-methyl- 2-0X0-1 , 3-dioxolen-4-yl) methyl-4 (1-hydroxy1-methylethyl) 2-propyl-1-{phenyl}4- [2-(trityltetrazol-5-yl) phenyl]methylimidazol-5-carboxylate obtained above was added. 35 liters of water was added. The reaction mass was then heated to 58 0C and maintained for 2 hours. Reaction completion was checked using thin layer chromatography. After the reaction was completed, the reaction mass was cooled to 33 0C and a solution of 18.9 kg of sodium chloride in 375 liters of water was added. The reaction mass was maintained at 33 0C for 30 minutes. The reaction mass was filtered and the filter bed was washed with a solution of 10 liters of acetic acid in 15 liters of water. The filtrate was taken into another reactor and 250 liters of dichloromethane was added. The reaction mass was stirred for 10 minutes and the organic layer was separated. The aqueous layer was extracted with 375 liters of dichloromethane in 3 equal lots. The combined organic layer was washed with a solution of 15 kg of sodium chloride, and 15 kg of sodium bicarbonate in 598 liters of water in two equal lots. The organic layer was again washed with a solution of 5 kg of sodium chloride in 100 liters of water in two equal lots. The organic layer was distilled off atmospherically and then under a vacuum of 650 mm Hg at a temperature of 40 0C to distill dichloromethane completely. The residue was then co-distilled with 50 liters of toluene in two equal lots. To the residue 242 liters of acetone was added . The reaction mass was heated to 55 0C and 140 liters of acetone was distilled from the reaction mass. The remaining reaction mass was cooled to 39 0C and 25 liters of acetone was distilled atmospherically. The reaction mass was then cooled to 35 0C and maintained for 1.5 hours. The reaction mass was filtered and the wet material was washed with 13 liters of acetone. The wet compound was taken into another reactor and 158 liters of acetone was added. The mixture was heated to 57 0C and maintained for 10 minutes. The reaction mass was filtered through a candy filter and 50 liters of solvent was distilled from it atmospherically. Another 25 liters of solvent was distilled from the reaction mass and it was cooled to 30 C and maintained for 1.5 hours. The separated solid was filtered and washed with 5 liters of acetone. The wet material was dried at a temperature of 80 0C for 3 hours to yield 9 kg of the title compound. (Yield 51.4%).Purity by HPLC: 99.72%. Olmesartan acid impurity: 0.05%.Olmesartan acetyl impurity: below LOD.Olmesartan dehydro impurity: 0.06%.Bis dioxolene impurity: less than 0.1 %. | |
With hydrogenchloride; In methanol; dichloromethane; at 0 - 5℃; for 1 - 2h; | METHOD 2: 10 g of (5-Methyl-2-oxo-1 , 3-dioxolen-4-yl) methyl-4 (1-hydroxy1- methylethyl) 2-propyl1-{phenyl}4-[2-(trityltetrazol-5-yl)phenyl]methylimidazol-5- carboxylate of Formula VII was added to a mixture of 20 ml methanol and 5 ml methylene chloride. 7.6 ml of a methanolic solution of hydrochloric acid (9% w/v) was added at 3 C to the above reaction mass. The reaction mixture was stirred at 0-5 C for 1 to 2 hours. The reaction mixture was diluted with water, neutralized with sodium hydroxide solution and stirred with a mixture of 250 ml toluene and 10 ml ethyl acetate. The precipitated product was filtered, and washed with water. The compound was dried at 70 to 80 C for 2 to 3 hours to get 5.2 g of the title compound. |
Tags: 1020157-01-0 synthesis path| 1020157-01-0 SDS| 1020157-01-0 COA| 1020157-01-0 purity| 1020157-01-0 application| 1020157-01-0 NMR| 1020157-01-0 COA| 1020157-01-0 structure
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