Description:FIELD OF INVENTION
The present disclosure relates to a process for the synthesis of Oxcarbazepine [10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide (1)].
BACKGROUND OF INVENTION
The background information herein below relates to the present disclosure but is not necessarily prior art.
Oxcarbazepine is useful as is a medication used to treat epilepsy. It is used for both focal seizures and generalized seizures in the treatment of epilepsy. Oxcarbazepine has been used both alone and as add-on therapy in patients with bipolar disorder who have had no success with other treatments. Oxcarbazepine is administered orally.
Oxcarbazepine, 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide (1), is a structural derivative of carbamazepine, with a ketone functional group on the dibenzazepine ring at the 10 position (10-keto).

Oxcarbazepine is synthesized by various conventional methods. The disadvantages of these methods are the use of toxic and hazardous chemicals, long production cycles, low-purity products, and low yield of the product resulting in high production costs. Thus, the conventional processes for synthesis of oxcarbazepine are not industrially attractive.
There is, therefore, felt a need to provide a process for the synthesis of oxcarbazepine, which mitigates the drawbacks mentioned herein above or at least provides a useful alternative.
OBJECTS OF INVENTION
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:
It is an object of the present disclosure to ameliorate one or more problems of the prior art or to at least provide a useful alternative.
An object of the present disclosure is to provide a process for the synthesis of oxcarbazepine.
Another object of the present disclosure is to provide a simple, economical and environment-friendly process for the synthesis of oxcarbazepine.
Still another object of the present disclosure is to provide a process for the synthesis of oxcarbazepine with a high purity and a high yield.
Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.
SUMMARY OF INVENTION
The present disclosure relates to a process for preparing oxcarbazepine [10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide (1)]. The process comprises the step of reacting 10-methoxy-5H-dibenzo[b,f]azepine (2) with at least one metal cyanate in the presence of at least one organic acid at a first predetermined temperature for a first predetermined time to obtain a reaction mixture comprising an intermediate; followed by subjecting the reaction mixture to acid hydrolysis using at least one mineral acid in at least one fluid medium at a second predetermined temperature for a second predetermined time period; followed by adding a base and separating the precipitate to obtain crude (1). The crude (1) obtained is purified using at least one purification medium to obtain (1).
DESCRIPTION OF THE DRAWINGS
For a more complete understanding of the invention, reference should now be made to the embodiments illustrated in greater detail in the accompanying drawings and described by way of embodiments of the invention.
Figure 1 illustrates the 1H-NMR of (1)
DETAILED DESCRIPTION OF INVENTION
The present disclosure relates to a process for the synthesis of oxcarbazepine [10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide (1)].
Embodiments are provided so as to thoroughly and fully convey the scope of the present disclosure to the person skilled in the art. Numerous details are set forth, relating to specific components, and methods, to provide a complete understanding of embodiments of the present disclosure. It will be apparent to the person skilled in the art that the details provided in the embodiments should not be construed to limit the scope of the present disclosure. In some embodiments, well-known processes, well-known apparatus structures, and well-known techniques are not described in detail.
The terminology used, in the present disclosure, is only for the purpose of explaining a particular embodiment and such terminology shall not be considered to limit the scope of the present disclosure. As used in the present disclosure, the forms "a,” "an," and "the" may be intended to include the plural forms as well, unless the context clearly suggests otherwise. The terms "comprises," "comprising," “including,” and “having,” are open ended transitional phrases and therefore specify the presence of stated features, integers, steps, operations, elements, modules, units and/or components, but do not forbid the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The particular order of steps disclosed in the method and process of the present disclosure is not to be construed as necessarily requiring their performance as described or illustrated. It is also to be understood that additional or alternative steps may be employed.
The terms first, second, third, etc., should not be construed to limit the scope of the present disclosure as the aforementioned terms may be only used to distinguish one element, component, region, layer or section from another component, region, layer or section. Terms such as first, second, third etc., when used herein do not imply a specific sequence or order unless clearly suggested by the present disclosure.
Oxcarbazepine is synthesized by various conventional methods. The disadvantages of these methods are the use of toxic and hazardous chemicals, long production cycles, low-purity products, and low yield of the product resulting in high production costs.
The present disclosure provides a simple, economical and environmentally-friendly process for the synthesis of oxcarbazepine [10-oxo-10,11-dihydro-5H-dibenzo[b, f]azepine-5-carboxamide (1)].
In an aspect, the present disclosure provides a process for preparing 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide (1),

(1)
The process of the present disclosure comprises at least the steps of
i.reacting 10-methoxy-5H-dibenzo[b,f]azepine (2)

(2)
with at least one metal cyanate in the presence of at least one organic acid at a first predetermined temperature for a first predetermined time to obtain a reaction mixture comprising an intermediate; followed by subjecting the reaction mixture to acid hydrolysis using at least one mineral acid in at least one fluid medium at a second predetermined temperature for a second predetermined time period; followed by adding a base and separating the precipitate to obtain crude (1); and
ii.purifying the crude (1) obtained in step (i) using at least one purification medium to obtain (1).
Step 1) Synthesis of (1)
In accordance with the present disclosure, the at least one metal cyanate is selected from sodium cyanate, potassium cyanate and chlorosulphonyl isocyanate.
In one embodiment of the present disclosure, the at least one metal cyanate is sodium cyanate.
In accordance with the present disclosure, the molar ratio of (2) and the at least one metal cyanate is in the range from 1.0:1.2 to 1.0:2.0.
In one embodiment of the present disclosure, the molar ratio of (2) and the at least one metal cyanate is 1.0:1.5.
In accordance with the present disclosure, the at least one organic acid is selected from acetic acid, benzoic acid, p-nitro benzoic acid, m-chloroacetic acid and mandelic acid.
In one embodiment of the present disclosure, the at least one organic acid is acetic acid. The weight ratio of (2) and acetic acid is in the range from 1.0:1.0 to 1.0:5.0.
In one embodiment of the present disclosure, the weight ratio of (2) and acetic acid is 1.0:3.0.
In one embodiment of the present disclosure, the at least one organic acid is benzoic acid. The mole ratio of (2) and benzoic acid is in the range of 1.0:1.0 to 1.0:2.0.
In one embodiment of the present disclosure, the mole ratio of (2) and benzoic acid is 1.0:1.2.
In accordance with the present disclosure, the first predetermined temperature is in the range of 30°C to 60°C.
In an exemplary embodiment of the present disclosure, the first predetermined temperature is 40°C.
In an exemplary embodiment of the present disclosure, the first predetermined temperature is 45°C.
In an exemplary embodiment of the present disclosure, the first predetermined temperature is 55°C.
In accordance with the present disclosure, the first predetermined time is in the range of 0.5 hour to 4 hours.
In an exemplary embodiment of the present disclosure, the first predetermined time is 3 hours.
In an exemplary embodiment of the present disclosure, the first predetermined time is 2 hours.
In an exemplary embodiment of the present disclosure, the first predetermined time is 1 hour.
In accordance with the present disclosure, the at least one mineral acid is selected from hydrochloric acid, and dilute sulphuric acid.
In one embodiment of the present disclosure, the at least one mineral acid is hydrochloric acid.
In one embodiment of the present disclosure, hydrochloric acid is concentrated HCl.
In accordance with the present disclosure, the weight ratio of (2) to the at least one mineral acid is in the range of 1.0:0.5 to 1.0: 2.0.
In one embodiment of the present disclosure, the weight ratio of (2) to the at least one mineral acid is 1.0:1.0.
In accordance with the present disclosure, the at least one fluid medium is selected from acetone, methyl isobutyl ketone and isopropyl alcohol.
In one embodiment of the present disclosure, the at least one fluid medium is acetone.
In accordance with the present disclosure, the second predetermined temperature is in the range of 30°C to 50°C.
In an exemplary embodiment of the present disclosure, the second predetermined temperature is 40°C.
In an exemplary embodiment of the present disclosure, the second predetermined time is in the range of 1 hour to 3 hours.
In one embodiment of the present disclosure, the second predetermined temperature is 2 hours.
In accordance with the present disclosure, the base is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate.
In one embodiment of the present disclosure, the base is sodium hydroxide.
The separation of the precipitate can be carried out by various techniques such as filtration.
In one embodiment of the present disclosure, the separation of the precipitate is carried out by filtration.
In one embodiment of the present disclosure, the base is added in the form of an aqueous solution.
The synthesis of 10-oxo-10,11-dihydro-5h-dibenzo [b,f] azepine-5-carboxamide according to the present disclosure can be carried out in conventional ways.
In one embodiment of the present disclosure, the synthesis of 10-oxo-10,11-dihydro-5h-dibenzo [b,f] azepine-5-carboxamide is carried out as a one-pot process.
Step 2) Purification of crude (1)
In accordance with the present disclosure, the at least one purification medium is selected from an organic acid and an organic solvent.
In accordance with the present disclosure, the at least one purification medium is an organic acid selected from formic acid, acetic acid, and mono chloroacetic acid.
In accordance with the present disclosure, when the at least one purification medium is an organic acid, the step of purifying crude (1) comprises mixing crude (1) with the organic acid and stirring the mixture, followed by adding water and separating the precipitate to obtain (1).
In one embodiment of the present disclosure, the organic acid is formic acid.
In one embodiment of the present disclosure, the organic acid is acetic acid.
In accordance with the present disclosure, the weight ratio of the crude (1) and the organic acid is in the range of 1.0:2.0 to 1.0:6.0.
In one embodiment of the present disclosure, the organic acid is formic acid and the weight ratio of the crude (1) and the organic acid is 1.0:3.0.
In one embodiment of the present disclosure, the organic acid is acetic acid and the weight ratio of the crude (1) and the organic acid is 1.0:4.0.
In accordance with the present disclosure, the weight ratio of the organic acid and water is in the range of 1.0:0.5 to 1.0:5.0.
In one embodiment of the present disclosure, the weight ratio of the organic acid and water is 1.0:1.0.
The separation of the precipitate can be carried out by various techniques such as filtration.
In one embodiment of the present disclosure, the separation of the precipitate is carried out by filtration.
In accordance with the present disclosure, the at least one purification medium is an organic solvent selected from isopropanol, methanol, acetonitrile, acetone, and ethyl acetate.
In one embodiment of the present disclosure, the organic solvent is isopropanol.
In one embodiment of the present disclosure, the organic solvent is methanol.
In one embodiment of the present disclosure, the organic solvent is acetonitrile.
In one embodiment of the present disclosure, the organic solvent is acetone.
In one embodiment of the present disclosure, the organic solvent is ethyl acetate.
In accordance with the present disclosure, when the at least one purification medium is an organic solvent, the step of purifying crude (1) comprises mixing crude (1) with the organic solvent and heating the mixture to a third predetermined temperature, followed by cooling and separating the precipitate to obtain (1).
In accordance with the present disclosure, the weight ratio of crude (1) to the organic solvent is in the range of 1.0:1.0 to 1.0:10.0.
In one embodiment of the present disclosure, the weight ratio of crude (1) to the organic solvent is 1.0:5.0.
In accordance with the present disclosure, the third predetermined temperature is in the range of 50°C to 60°C.
In an exemplary embodiment of the present disclosure, the third predetermined temperature is 55°C.
In an exemplary embodiment of the present disclosure, the third predetermined temperature is 50°C.
The separation of the precipitate can be carried out by various techniques such as filtration.
In one embodiment of the present disclosure, the separation of the precipitate is carried out by filtration.
In accordance with the present disclosure, the purity of (I) is in the range of 95.00 to 99.99 % according to HPLC analysis.
In one embodiment the present disclosure, the purity of (I) is in the range of 99.00 to 99.99 % according to HPLC analysis.
In accordance with the present disclosure, the yield of (I) is in the range of 85.0 to 95.00 wt%.
The process of the present disclosure employs inexpensive and easily available reagents. The process of the present disclosure employs environmentally-friendly reagents. Thus, the process of the present disclosure is economical.
The foregoing description of the embodiments has been provided for purposes of illustration and not intended to limit the scope of the present disclosure. Individual components of a particular embodiment are generally not limited to that particular embodiment, but, are interchangeable. Such variations are not to be regarded as a departure from the present disclosure, and all such modifications are considered to be within the scope of the present disclosure.
The present disclosure is further described in light of the following experiments which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure. The following experiments can be scaled up to industrial/commercial scale and the results obtained can be extrapolated to industrial scale.
Methods
Purity of (1) was determined using HPLC analysis.
HPLC method
Related Substances by HPLC.
Limits:
Carbamazepine Not more than 0.5%
Oxcarbazepine Related compound E Not more than 0.05%
Methoxycarbamazepine b (OXP1) Not more than 0.05%
Carbamazepine related compound B Not more than 0.05%
Methoxydibenzazepin (10MISB) Not more than 0.05%
Any Individual unspecified impurity Not more than 0.05%
Total Impurities Not more than 1.0%

A) Preparation of Mobile Phase

Buffer: 6.8 gm of potassium dihydrogen phosphate (KH2PO4) and 2.0 ml triethyl amine (TEA) were added to 1000 ml HPLC water. The mixture was sonicated and pH was adjusted to 6.0 + 0.1 with dilute orthophosphoric acid.

Mobile Phase A: Buffer: Methanol: Acetonitrile (930: 330 : 240)

Mobile Phase B: Acetonitrile

B) Chromatographic Condition:

Column Inertsil ODS-3, 100°A (250 mm x 4.6 mm, 5 µm) or equivalent
Column Temperature 50°C + 2°C
Flow Rate 1.5 mL/min (Isocratic mode)
Injection Volume 10 L
Detector Wavelength 215 nm
Run Time 85 minutes
Retention Time Oxcarbazepine is 8.4 minutes
Needle wash Water: Acetonitrile (2:8)

B)Preparation of Solution:

System Suitability Solution:
5 mg of each of Methoxydibenzazepin (10MISB), Carbamazepine USP RS and Oxcarbazepine USP RS or working standard were transferred to a 50 ml volumetric flask. About 40 ml diluent was added and the resultant mixture was sonicated to dissolve the solute, followed by adding solvent to make up to the mark and mixing.
Preparation of standard stock solution:
25.0 mg of Oxcarbazepine USP RS or working standard was transferred to 50.0 ml volumetric flask, and it was dissolved by sonication in diluent. The volume was made upto the mark with same diluent and mixed well.
Preparation of Standard solution:
1.0 ml of the standard stock solution was transferred to 100.0 ml volumetric flask. The volume was made up to the mark with diluent, and mixed well. Further 1 ml of this solution was transferred to 20.0 ml volumetric flask, the volume was made up to the mark with the same diluent, and mixed well.
Preparation of sample solution:
25.0 mg of test sample was transferred to 50.0 ml volumetric flask and dissolved by sonication in the diluent and the volume was made up to the mark with same diluent, and mixed well.

Injection Sequence:

Sl# Description No. of Injections Run Time in minute
1 Blank 1 85
2 System suitability solution 1
3 Blank 1
4 Standard solution 5 15
5 Test solution-1 1 85
6 Test solution-2 1

Procedure
The HPLC system was equilibrated with the initial composition until a steady baseline was obtained. Blank, System suitability solution and standard solution were injected, and it was ensured that the system suitability parameters met the requirements. The blank and test solution were injected in duplicate into the chromatogram as per the injection sequence and the chromatograms were recorded.

Retention time

Analyte RRT RRF
Oxcarbazepine 1.0 1.0
Carbamazepine 1.7 1.9
Oxcarbazepine Related compound E 2.1 1.2
Methoxycarbamazepine b (OXP1) 2.5 1.6
Carbamazepine related compound B 7.4 1.3
Methoxydibenzazepin (10MISB) 7.9 1.5
Any Individual unspecified impurity NA 1.0

System Suitability acceptance criteria:
Resolution: The resolution between the peak due to Oxcarbazepine and Carbamazepine in System suitability solution should not be less than 8.0.
% RSD: The percentage relative standard deviation of area of five replicate injections for the peak due to oxcarbazepine in the chromatogram obtained with standard solution should not be more than 10.0%.

Note: Disregard any peak due to blank

Calculation:
Calculate the percentage content of impurity by formula mentioned below:

AC x WS x 1 x 1 x 50
% known Impurities = --------------------------------------------- x P
AS x 50 x 100 x 20 x WT x RRF

AU x WS x 1 x 1 x 50
% Any individual Impurity = -------------------------------------------- x P
AS x 50 x 100 x 20 x WT x RRF

AI x WS x 1 x 1 x 50
% Total Unknown Impurities = -------------------------------------- x P
AS x 50 x 100 x 20 x WT
Where,
AU = Average peak area of unspecified impurity in test solution.
AK = Average peak area of known impurity in test solution.
AS = Average peak area of oxcarbazepine in standard solution.
WS = Weight in mg of oxcarbazepine working standard taken for standard solution preparation.
AI = Sum of peak area of all unknown impurities in test solution.
WT = Weight in mg of test sample taken for test solution preparation.
P = Potency of oxcarbazepine working standard.
RRF = Relative response factor of respective know impurity as given in table.
EXPERIMENTAL DETAILS
Preparation of 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide (1)
Example 1
A RBF was charged with acetic acid (300 ml) and 10-methoxy-5H-dibenzo[b, f]azepine (2) (100.0 g, 0.44 mole). 85% Sodium cyanate (45.5 g, 0.69 mole) was added at 25°C in four lots over a period of 2 hours. The reaction mass was stirred and maintained at 40°C for 3 hours.
After completion of the reaction were added acetone (76.0 ml) and con. HCl (100.0 ml) at 40°C and the resultant mixture was stirred for 2 hours. Sodium hydroxide (107.0 g, 2.67 mole) solution in water (300 ml) was added to the mixture. The solid obtained was filtered and washed with purified water (100 ml) and acetone (100 ml) to obtain 98.0 g of crude 10-oxo-10,11-dihydro-5H-dibenzo [b,f] azepine-5-carboxamide (1) having a purity of 95.31% by HPLC analysis.
Purification of crude (1) using formic acid
To a RBF were added crude (1) obtained above and 98% formic acid (300 ml) followed by stirring for 1 hour. The insoluble solid was filtered off. Purified water (300 ml) was slowly added to the filtrate to produce crystals of pure (1). The precipitated solid was filtered and dried to obtain 95.0 g of pure (1) having a purity of 99.80% by HPLC analysis.
Example 2
A RBF was charged with acetic acid (300 ml) and 10-methoxy-5H-dibenzo[b,f] azepine (2) (100g, 0.44 mole). 85% Sodium cyanate (45.5 g, 0.69 mole) was added at 25°C in four lots over a period of 2 hours. The reaction mass was stirred and maintained at 55°C for 1 hour.
After completion of the reaction were charged acetone (76.0 ml) and con. HCl (100.0 ml) at 40°C and the reaction mass was stirred for 2 hours. Sodium hydroxide (107 g, 2.67 mole) solution in water (300 ml) was added to the above mass. The solid obtained was filtered and washed with purified water (100 ml) and acetone (100 ml) to obtain 98.0 g of crude (1) having a purity of 92.90% by HPLC analysis.
Purification of crude (1) using acetic acid
To a RBF were added crude (1) obtained above and acetic acid (400 ml) and stirred for 1 hour. The insoluble solid was filtered off. Purified water (400 ml) was slowly added to the filtrate to provide crystals of pure (1). The solid was filtered and dried to obtain 90.0 g of pure (1) having a purity of 99.93% by HPLC analysis.
Example 3
A RBF was charged with benzoic acid (65.50 g, 0.53 mole) and 10-methoxy-5H-dibenzo[b,f]azepine (2) (100.0g, 0.44 mole). 85% Sodium cyanate (45.5 g, 0.69 mole) was added at 25°C in four lots over a period of 2 hours. The reaction mass was stirred and maintained at 55°C for 1 hour.
After completion of reaction were charged acetone (76.0 ml) and con. HCl (100.0 ml) at 40°C and the reaction mass was stirred for 2 hours. Sodium hydroxide (107.0 g, 2.67 mole) solution in water (300 ml) was added. The solid obtained was filtered and washed with purified water (100 ml) and acetone (100 ml) to obtain 95 g of crude (1) having a purity 99.72% by HPLC analysis.
Purification of crude (1) in formic acid
To a RBF were added 95.0 g of crude (1) and formic acid (400.0 ml) followed by stirring for 1 hr. The insoluble solid was filtered off. Purified water (400.0 ml) was slowly added to provide crystals of pure (1). The solid was filtered and dried to obtain 88.0 g of pure (1) having a purity of 99.94% by HPLC.
Example 4
A RBF was charged with acetic acid (300.0 ml) and 10-methoxy-5H-dibenzo [b,f] azepine (2) (100.0g, 0.44 mole). 85% Sodium cyanate (45.5 g, 0.69 mole) was added to the RBF at 25°C in four lots over a period of 2 hours. The reaction mass was stirred and maintained at 45°C for 2 hours.
After completion of the reaction, were charged acetone (76.0 ml) and conc. HCl (100.0 ml), the resultant mass was stirred at 40°C for 2 hours. Sodium hydroxide (107.0 g, 2.67 mole) solution in water (300 ml) was added. The solid was filtered and washed with purified water (100 ml) and acetone (100 ml) to obtain 98.0 g of crude (1) having a purity of 95.82% by HPLC analysis.
4A) Purification of crude (1) using isopropanol
To a RBF were charged crude 100 g (1) and isopropanol (500 ml) and the resultant mass was heated and stirred at 55°C for 1 hour. The resultant mass was cooled to 25°C and stirred for 1 hr. The solids were filtered to obtain 85 g of (1) having a purity of 99.27% by HPLC analysis.
4B) Purification of crude (1) using methanol
To a RBF, were charged crude 100 g (1) and methanol (500 ml) and the resultant mass was heated and stirred at 55°C for 1 hour, the resultant mass was cooled to 25°C and stirred for 1 hour. The solids were filtered to obtain 95 g of (1) having a purity of 99.28% by HPLC.
4C) Purification of crude (1) using acetonitrile
A RBF was charged with 100.0 g of crude (1) and acetonitrile (500 ml). The resultant mass was heated and stirred at 50°C for 1 hour. The resultant mass was cooled to 25°C and stirred for 1 hour. The precipitated solid was filtered to obtain 85.0 g of (1) having a purity 99.53% by HPLC analysis.
4D) Purification of crude (1) using acetone
A RBF was charged with 100.0 g of crude (1) and acetone (500 ml). The resultant mass was heated at 50°C and stirred for 1 hour. The reaction mass was cooled to 25°C and stirred for 1 hour. The precipitated solids were filtered and dried to obtain 90.0 g of (1) having a purity of 99.57% by HPLC analysis.
From above, it is clear that the above process step along with the process parameters such as temperature range and purification medium played an effective role in achieving higher yield and purity.
TECHNICAL ADVANCEMENTS
The present disclosure described herein above has several technical advantages including, but not limited to, the realization of a process for the synthesis of 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide (1), which:
-is feasible for large scale manufacturing;
-is simple, economical and environment-friendly;
-Provides high yield and high purity 10-oxo-10,11-dihydro-5H-dibenzo[b, f]azepine-5-carboxamide (1); and
-is carried out as a one-pot process.
The embodiments herein and the various features and advantageous details thereof are explained with reference to the non-limiting embodiments in the following description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.
The foregoing description of the specific embodiments so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the disclosure to achieve one or more of the desired objects or results.
Any discussion of documents, acts, materials, devices, articles or the like that has been included in this specification is solely for the purpose of providing a context for the disclosure. It is not to be taken as an admission that any or all of these matters form a part of the prior art base or were common general knowledge in the field relevant to the disclosure as it existed anywhere before the priority date of this application.
The numerical values mentioned for the various physical parameters, dimensions or quantities are only approximations and it is envisaged that the values higher/lower than the numerical values assigned to the parameters, dimensions or quantities fall within the scope of the disclosure, unless there is a statement in the specification specific to the contrary.
While considerable emphasis has been placed herein on the components and component parts of the preferred embodiments, it will be appreciated that many embodiments can be made and that many changes can be made in the preferred embodiments without departing from the principles of the disclosure. These and other changes in the preferred embodiment as well as other embodiments of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation. ,
Claims:WE CLAIM:
1.A process for preparing 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide (1),

(1)
the process comprising at least the steps of:
i.reacting 10-methoxy-5H-dibenzo[b,f]azepine (2)

(2)
with at least one metal cyanate in the presence of at least one organic acid at a first predetermined temperature for a first predetermined time to obtain a reaction mixture comprising an intermediate; followed by subjecting the reaction mixture to acid hydrolysis using at least one mineral acid in at least one fluid medium at a second predetermined temperature for a second predetermined time period; followed by adding a base and separating the precipitate to obtain crude (1); and
ii.purifying the crude (1) obtained in step (i) using at least one purification medium to obtain (1).
2.The process as claimed in claim 1, wherein the at least one metal cyanate is selected from sodium cyanate, potassium cyanate and chloro sulphonyl isocyanate.
3.The process as claimed in claim 1, wherein the molar ratio of (2) and the at least one metal cyanate is in the range from 1.0:1.2 to 1.0:2.0.
4.The process as claimed in claim 1, wherein the at least one organic acid is selected from acetic acid, benzoic acid, p-nitro benzoic acid, m-chloroacetic acid and mandelic acid.
5.The process as claimed in claim 1, wherein the first predetermined temperature is in the range of 30°C to 60°C.
6.The process as claimed in claim 1, wherein the first predetermined time is in the range of 0.5 hour to 4 hours.
7.The process as claimed in claim 1, wherein the at least one mineral acid is selected from hydrochloric acid, and dilute sulphuric acid.
8.The process as claimed in claim 1, wherein the at least one fluid medium is selected from acetone, methyl isobutyl ketone and isopropyl alcohol.
9.The process as claimed in claim 1, wherein the second predetermined temperature is in the range of 30°C to 50°C.
10.The process as claimed in claim 1, wherein the second predetermined time is in the range of 1 hour to 3 hours.
11.The process as claimed in claim 1, wherein the base is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate.
12.The process as claimed in claim 1, wherein the at least one purification medium is selected from an organic acid and an organic solvent.
13.The process as claimed in claim 1, wherein the at least one purification medium is an organic acid selected from formic acid, acetic acid, and mono-chloroacetic acid.
14.The process as claimed in claim 13, wherein the step of purifying crude (1) comprises mixing crude (1) with the organic acid and stirring the mixture, followed by adding water and separating the precipitate to obtain (1).
15.The process as claimed in claim 1, wherein the at least one purification medium is an organic solvent selected from isopropanol, methanol, acetonitrile, acetone, and ethyl acetate.
16.The process as claimed in claim 15, wherein the step of purifying crude (1) comprises mixing crude (1) with the at least one organic solvent and heating the mixture to a third predetermined temperature, followed by cooling and separating the precipitate to obtain (1).
17.The process as claimed in claim 15, wherein the third predetermined temperature is in the range of 50°C to 60°C.
18.The process as claimed in claim 1, wherein the purity of (1) is in the range of 95.00 to 99.99 % according to HPLC analysis.
19.The process as claimed in claim 1, wherein the yield of (1) is in the range of 85.0 to 95.00 wt%.
The process as claimed in claim 1, wherein step (i) is carried out as a one pot process.
20. The process as claimed in claim 1, wherein step (i) is carried out as a one potprocess.