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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.
Oxcarbazepine is a voltage-gated sodium channel blocker with IC50 of 160 μM and it is used for the treatment of partial seizure.
Synonyms: GP 47680
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Batch number can be found on the product's label following the word 'Batch'.
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Search for reports by entering the product batch number.
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CAS No. : | 28721-07-5 |
Formula : | C15H12N2O2 |
M.W : | 252.27 |
SMILES Code : | O=C(N1C2=CC=CC=C2CC(C3=CC=CC=C31)=O)N |
Synonyms : |
GP 47680
|
MDL No. : | MFCD00865307 |
InChI Key : | CTRLABGOLIVAIY-UHFFFAOYSA-N |
Pubchem ID : | 34312 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
* 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 |
---|---|---|
73.0% | With hydrogenchloride; In water; at 25 - 85℃; for 4 - 6h; | To the organic layer resulting from Example 1A was added 2N HCl (50.0 ml) and the reaction mass was maintained at a temperature ranging from about 40 C. to about 50 C. for about 4 to about 6 hours. After completion of the reaction (detected by TLC) the reaction mass was cooled to a temperature ranging from about 0 C. to about 5 C. for about one hour and the separated solids were filtered and washed with dichloromethane (15.0 ml). Purification: To a 3 L 4-necked round bottom flask was added 1125 ml of methanol and 75 gm crude oxcarbazepine prepared by the process of Example 1B and stirred at room temperature, about 25 C. to about 30 C. The reaction mass slurry was heated to reflux, a temperature of about 65 C., and further stirred for about 30 to about 40 minutes. 450 ml acetic acid was added under reflux which resulted in a clear solution. The solution was stirred under reflux at a temperature of about 70 C. for about 30 to about 40 minutes. 7.5 g of charcoal was added to the solution and stirred under reflux for about 20 to about 30 minutes. The reaction mass was filtered and washed twice in a hyflow bed with 75 ml of acetic acid and methanol in a 2:5 ratio at a temperature of about 70 C. The filtrate was cooled in a 3 L 4-necked round bottom flask to a temperature of about 30 C. for about 1 hour, and further cooled to a temperature of about 0 C. for about 30 min. The precipitated product was filtered and dried to get pure oxcarbazepine. Yield=73.0%, m.p. 222 C., purity>99.5%, 1H NMR Spectrum (CDCl3, TMS as internal standard) shows 6 at 3.3 (1H,d), 4.4(1H,d), 5.0(2H.br.s), 7.2-8.2 (8H,m&d).EXAMPLE 2B Preparation of Oxcarbazepine The residue obtained in Example 2A was transferred to a 2 L 4-necked round bottom flask and 500 ml of 2N aqueous HCl was added at a temperature ranging from about 25 C. to about 30 C. The reaction mass was heated to a temperature ranging from about 80 C. to about 85 C. and maintained for between 4 to 5 hours. After completion of the reaction (detected by HPLC/TLC), the reaction mass was cooled to a temperature ranging from about 50 C., and 500 ml of toluene was charged to the reaction mass and maintained for 30 minutes at a temperature of about 50 C. The reaction mass was further stirred at a temperature ranging from about 25 C. to about 30 C. for about 30 minutes. The solids were filtered, separated, and then washed twice with 100 ml of toluene. The product was dried to get crude oxcarbazepine of 97-98% purity as determined by HPLC. Purification: The purification of the oxcarbazepine prepared in Example 2A was carried in substantially the same manner as in Example 1. |
With hydrogenchloride; In water; toluene; at 20 - 89℃; for 0.25h; | In a three-neck flask (500 ml), equipped with a mechanical stirring apparatus, 15 ml water was introduced, followed by pyridinium bromide (71.75 g, 0.45 mole; Chemadaa' (Nir Yitshak, Israel) ). The mixture was stirred at room temperature [(22 C)] for about 10 minutes. Then 250 ml toluene was added, followed by 50 g (0.224 mol) of [10-METHOXY-5H-] dibenz [[BZF] AZEPINE] (compound of formula (4), wherein R4 is methoxy). [Note: 10-methoxy-5H- dibenz [[B, T] AZEPINE] may be obtained from [IMINOSTILBENE] according to the process disclosed in U. S. Patent No. 5,808, 058. [10-METHOXY-5H-DIBENZ [B FLAZEPINE] also is commercially available from various suppliers, including Zhejiang Jiuzhou Pharmaceutical Co. , Ltd. (Zhejiang, China), and Ningbo Chongyangtang Biologic Tech Co. , Ltd. (Ningbo, China)] [NAOCN] (45 g, 0.69 mol ; OCI Corp. , South Korea) was added and the reaction was mixed for about 7-8 hours at room temperature [(22C).] After [7-8] hours, [125ML] of water was added, and the mixture was stirred for about 15 minutes. The resulting solid carbamate of formula (1), 10-methoxy-5H- dibenz [[B2TAZEPINE-5-CARBOXAMIDE,] was filtered and washed with 50 ml of water. The organic layer was separated and washed with water (2 x [50ML).] In a 500 ml three necked flask, the organic phase from above was introduced, to which the solid carbamate of formula (1) [(10-METHOXY-5H-DIBENZ [B2FLAZEPINE-5-CARBOXAMIDE)] was added to form a slurry. The mixture was heated to 89 C to clarify the solution, and 250 ml of 10% [HC1] was added dropwise with stirring. When thin layer chromatography indicated that the intermediate carbamate of formula (1) had been substantially consumed, the reaction mixture was cooled to room temperature and the mixture was stirred at this temperature for 15-30 minutes. The product, [10-OXO-10,] [11-DIHYDRO-5H-DIBENZ [B2FLAZEPINE-5-CARBOXAMIDE] (oxcarbazepine), was filtered and the crude oxcarbazepine cake was thoroughly washed with water until the pH reached 6-7. The mixture was then washed with toluene (50 ml), and the solids were dried to yield 34.4 g (0.137 mol) crude oxcarbazepine as a yellow-brown powder (yield relative to (2) is [61%).] The crude oxcarbazepine was slurried in 408 ml of boiling 80: 20 isopropanol : water for about 1 hour. The solid was separated by filtration and dried to afford 30.6 g oxcarbazepine [(89%] purification yield). Further purification was carried out in 765 ml of boiling 80: 20 isopropanol: water, hot filtration and cooling to room temperature. Filtration and drying of the solid precipitate afforded 26.5 g of purified oxcarbazepine (yield relative to starting material (2) is 47%, and purification yield is 87%). | |
With hydrogenchloride; In water; isopropyl alcohol; at 20 - 82℃; for 2h; | The carbamoylation reaction was performed as in Example 1, except that [150] ml toluene was used instead of 250 ml. The resulting solid carbamate of formula (1), 10-methoxy-5H- dibenz [[B2FLAZEPINE-5-CARBOXAMIDE,] was isolated as described in Example 1. In a three necked flask, 330 ml of isopropyl alcohol, 78 ml of 12% HCl, and the solid 10- [METHOXY-SH-DIBENZ [B2FLAZEPINE-S-CARBOXAMIDE] were introduced. The mixture was heated to [78] [- 82 C] for about 1 hour. When TLC indicated that the carbamate of formula (1) was consumed, the reaction mixture was cooled to room temperature and stirred for 1 hour. The separated solids were filtered and washed with water to provide crude 10-oxo-10, [11-DIHYDRO-SH-DIBENZ [BFLAZEPINE-S-] carboxamide (oxcarbazepine), which was purified as described in Example 1. Yield relative to starting material of formula (2) was 43-45%. |
With o-toluenesulfonic acid; In 1,2-dichloro-ethane; at 20 - 80℃; for 4h; | Step 3 Preparation of cxcarbazepine-from 10-Methoxy-5H-dibenz (b, f) azepine 5- carboxamide 85 gm of 10-Methoxy-5H-dibenz [b, fj azepine-5-carboxamide is dissolved in 425 ml of ethylene dichloride. To this 800 mi of 2N o-toluene sulfonic acid is added and heated to 75-80C & maintained for bout 3 hours. It is then cooled to 20C & maintained for about 1 hour. The product oxcarbazepine is separated by filtration. This is then purified in acetone-water to yield 55 gms of pure oxcarbazepine. | |
Preparation of oxcarbazepine (I) 600 ml of water are added to the round-bottomed flask containing the suspension of 10- methoxy-5H-dibenzo [b, faazepine-5-carboxamide (IV) from Example 1, and about 12 g of 37% HC1 are added dropwise to pH = 1. The suspension is stirred at about 95 DEG C for 4 hours. The mixture is cooled to 25 DEG C and about 14 g of 30% NaOH are added dropwise to bring the pH from 1.0 to 7.0-7. 5. The reaction suspension is filtered at 25 DEG C and the cake is washed twice with water (2 x 100 ml), the filtration and washing waters then being removed. The cake is washed three times with methanol (3 x 100 ml) at 12-14 DEG C and the waters are then removed. The wet cake (160-170 g) is suspended in dimethylacetamide (400 ml) while heating at 110 DEG C until the solid has dissolved. The product is filtered off at a temperature above 80 DEG C (temperature of start of recrystallization). The filtrate is cooled to 60 DEG C, 400 ml of methanol are then added to the suspension, and the resulting mixture is cooled first to 25 DEG C and then to 0-5 DEG C. After 1 hour at 0-5 DEG C, the cake is washed with 150 ml of methanol at 12-14 DEG C and the methanolic washing phase is removed. The cake is dried under vacuum at 40 DEG C for 6 hours. | ||
With water; oxalic acid; at 90℃; for 17h;Product distribution / selectivity; | b) Preparation of Oxcarbazepine from 10-methoxy carbamazepine; 100 g of <strong>[28721-09-7]10-methoxycarbamazepine</strong> in 1000 ml water and 69.24 g of oxalic acid solution was heated to 9O0C and maintained for about 17 hrs. After completion of the reaction the reaction mixture was cooled to room temperature (RT). The resulting reaction mass was filtered and washed with 1000 ml of DM water. The wet material obtained was charged with isopropyl alcohol and DM water. The obtained reaction mixture was heated to reflux for about 2 h. the reaction mixture was cooled to 15- 250C, filtered and washed with 100 ml of IPA-water mixture. The resulting compound is dried at 6O0C for 6 h to produce 90 g of Oxcarabzepine. | |
With hydrogenchloride; In methanol; water; at 75 - 80℃; | The crude [XXI] was taken in a RB flask and methanol (600 ml) was added. The reaction mixture was heated to reflux. The reaction mixture was cooled, methanol was distilled off and toluene (50 ml) was added and further distilled. The residual [XXI] was cooled and toluene (500 ml) was added and stirred. Water was added followed by addition of cone. HCl. The reaction mixture was heated at 75-80C. The reaction mixture was cooled and the crude oxcarbazepine [I] was filtered, washed with toluene, 5% NaHCO3 and DM water and vacuum dried to give crude oxcarbazepine of formula[I] (yield = 82 g). The oxcarbazepine thus formed can be purified by dissolving in methanol (600 ml). The reaction mixture was stirred for 15-20 min. The pH of the <n="16"/>reaction mixture was maintained in the range of 7.5-8.5. The reaction mixture was stirred and heated to reflux at 65-70C for 2 h, and cooled, filtered and washed with methanol and dried to give oxcarbazepine [I], which was further purified by heating in methanol (1400 ml) and dichlormethane (1400 mL). The reaction mixture was refluxed for 30 min and treated with activated carbon. The reaction mixture was filtered through Hyflo bed and washed with methanol and dichloromethane mixture (1:1). The solvent was distilled to residual volume of 1000 mL. The reaction mixture was cooled and maintained. The reaction mixture was filtered through buchner funnel and washed with methanol and dried under vacuum at 50-60C to give pure oxcarbazepine (90 g). | |
With water;oxalic acid; at 90℃; for 19h;Reflux;Product distribution / selectivity; | b) Preparation of Oxcarbazepine from 10-methoxy carbamazepine 100 g of <strong>[28721-09-7]10-methoxycarbamazepine</strong> in 1000 ml water and 69.24 g of oxalic acid solution was heated to 90 C. and maintained for about 17 hrs. After completion of the reaction the reaction mixture was cooled to room temperature (RT). The resulting reaction mass was filtered and washed with 1000 ml of DM water. The wet material obtained was charged with isopropyl alcohol and DM water. The obtained reaction mixture was heated to reflux for about 2 h. the reaction mixture was cooled to 15-25 C., filtered and washed with 100 ml of IPA-water mixture. The resulting compound is dried at 60 C. for 6 h to produce 90 g of Oxcarabzepine. |
Tags: Oxcarbazepine | GP 47680 | Drug Standard | Amides | Sodium Channel | Organic Building Blocks | Drug Analysis | Membrane Transporter/Ion Channel | 28721-07-5
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