Title of Invention

PROCESS FOR PRODUCING 10-OXO-10,11-DIHYDRO-5H-DIBEMZ[B,F]AZEPINE-5-CARBOXAMIDE

Abstract This invention in general relates to the process for producing 10-oxo-10,11-dihydro- 5H-dibenz[b,/]azepine-5-carboxamide (oxcarbazepife). In particular the present invention provides novel intermediates to produce oxfarbazepine.
Full Text


We Claim;
1. A process for producing 10-oxo-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide of formula [I],
(Formula Removed)
via novel intermediates of formula [XIX] and [XX];
(Formula Removed)
wherein the process comprising:
(a) alkoxyhalogenating the 5H-dibenz[b,f]azepine-5- carbonitrile
of formula [VIII] to obtain 11 -alkoxy-10-halo-10,11 -dihydro-5H-dibenzo [b,f]
azepine-5-carbonitrile compound of formula [XIX],
(Formula Removed)
wherein R is C1-C3 alkyl chain; X is Cl, Br, I or F and alkoxyhalogenation reaction is carried out in presence of halogenating agent;
(b) dehydrohalogenating the 11 -alkoxy-10-halo-10,11 -dihydro-5H-
dibenzo[b,f] azepine-5-carbonitrile compound of the formula [XIX] in
presence of organic or inorganic base to obtain 10-methoxy-5H-
dibenz[b,f]azepine-5-carbonitrile of formula [XX],
(Formula Removed)
wherein R is C1-C3 alkyl chain and X is Cl, Br, I or F; and
(c) hydrolyzing the resultant compound [XX] in presence of an acid or base to get the pure 10-oxo-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide of formula [I].
2. The process as claimed in claim 1, wherein the halogenating agent is selected from the group comprising 1,3-dihalo-dimethylhydantoin, N-halosuccinimide, N-haloacetamide and 1,3-haloisocyanuric acid, alone or in combination thereof.
3. The process as claimed in claim 1, wherein the alkoxyhalogenation reaction is carried out in presence of an organic solvent.
4. The process as claimed in claim 1, wherein the organic solvent is selected from lower alcohols.
5. The process as claimed in claim 4, wherein the lower alcohol is selected from a group comprising methanol, ethanol or propanol, alone or mixture thereof.
6. The process as claimed in claim 1, wherein the organic base is selected from diethylamine, triethylamine, pyridine, 1,8-diazabicyclo [2.2.2] octane, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,8-diazabicyclo [5.4.0] undec-7-ene, N-methyl morpholine, N-methylpiperidine, or tetramethylguanidine alone or a mixture thereof.
7. The process as claimed in claim 1, wherein the inorganic base is selected from alkali or alkaline earth metal alkoxides, hydroxides, carbonates or bicarbonates.
8. The process as claimed in claim 7, wherein the inorganic base is preferably selected from lithium, sodium, potassium, calcium or magnesium.
9. The process as claimed in claim 1, wherein 5H-dibenz[b,f]azepine-5-
carbonitrile of formula [VIII] is prepared by a process comprising:
cyanating 5H-dibenz[b,f]azepine compound of formula [VII];
(Formula Removed)
with a suitable cyanating agent.
10. The process as claimed in claim 1, wherein 5H-dibenz[b,f]azepine-5-
carbonitrile of formula [VIII] is prepared by a process comprising:
dehydrating 5H-dibenz[b,f|azepine-5-carboxamide compound of formula [V];
(Formula Removed)
in presence of any suitable dehydrating agent.
11. An intermediate 11 -alkoxy-10-halo-10,11 -dihydro-5H-dibenzo[b,f] azepine-5-
carbonitrile of formula [XIX] as defined in claim 1 used in the preparation of 10-oxo-10,l 1-
dihydro-5H-dibenz[b,f] azepine-5-carboxamide of formula [I];
(Formula Removed)
wherein R is C1-C3 alkyl chain; and X is Cl, Br, I or F.
12. A process for preparing 11-alkoxy-10-halo-10,11-dihydro-5H-dibenzo[b,f] azepine-5-carbonitrile of formula [XIX] as claimed in claim 11 used in the preparation of 10-oxo-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide of formula [1];
(Formula Removed)
wherein R is C1-C3 alkyl chain and X is Cl, Br, I or F; the process comprising;
(a) cyanating 5H-dibenz[b,f|azepine compound of formula [VII]
(Formula Removed)
with a suitable cyanating agent to obtain 5H-dibenz[b,f]azepine-5-carbonitrile of formula [VIII]
(Formula Removed)
(b) alkoxyhalogenating the 5H-dibenz[b,f]azepine-5-carbonitrile of
formula [VIII] in presence of halogenating agent to obtain 11-alkoxy-10-halo-
10,11-dihydro-5H-dibenzo[b,f] azepine-5-carbonitrile compound of formula
[XIX].
13. The process as claimed in claim 12, wherein the halogenating agent is selected from the group comprising 1,3-dihalo-dimethylhydantoin, N-halosuccinimide, N-haloacetamide or 1,3-haloisocyanuric acid alone or in combination thereof.
14. The process as claimed in claim 12, wherein the alkoxyhalogenation reaction is carried out in presence of an organic solvent.
15. The process as claimed in claim 14, wherein the organic solvent is selected from lower alcohols.
16. A process for preparing H-alkoxy-10-halo-10,11-dihydro-5H-dibenzo[b,f] azepine-5-carbonitrile of formula [XIX] as claimed in claim 11 used in the preparation of 10-oxo-10,11 -dihydro-5H-dibenz[b,f]azepine-5-carboxarnide of formula [ 1 ];
(Formula Removed)
wherein R is C1-C3 alkyl chain and X is Cl, Br, I or F; the process comprising;
(a) dehydrating 5H-dibenz[b,f]azepine-5- carboxamide compound
of formula [V]
with a suitable dehydrating agent to obtain 5H-dibenz[b,f]azepine-5-carbonitrile of formula [VIII]
(Formula Removed)
(b) alkoxyhalogenating the 5H-dibenz[b,f]azepine-5-carbonitrile
of formula [VIII] in presence of halogenating agent to obtain 11-alkoxy-10-
halo-10,11-dihydro-5H-dibenzo[b,f] azepine-5-carbonitrile compound of formula [XIX].
17. The process as claimed in claim 16, wherein said dehydrating agent is selected from group comprising P2O5 or POCl3 or SOCl2 or a mixture thereof.
18. The process as claimed in claim 16, wherein said halogenating agent is selected from the group comprising 1,3-dihalo-dimethylhydantoin, N-halosuccinimide, N-haloacetamide or 1,3-haloisocyanuric acid alone or in combination thereof.

19. The process as claimed in claim 16, wherein the alkoxyhalogenation reaction is carried out in presence of an organic solvent.
20. The process as claimed in claim 19, wherein the organic solvent is selected from lower alcohols.
21. An intermediate 10-alkoxy-5H-dibenz[b,f|azepine-5-carbonitrile compound of formula [XX] as defined in claim 1 used in the preparation of 10-oxo-10,11 -dihydro-5H-dibenz[b,f] azepine-5-carboxamide of formula [I];
(Formula Removed)
wherein, R is C1-C3 alkyl chain
22. A process for preparing 10-alkoxy-5H-dibenz[b,f]azepine-5-carbonitrile
compound of formula [XX] as claimed in claim 21 used in the preparation of 10-oxo-10,11-
dihydro-5H-dibenz[b,f]azepine-5-carboxamide of formula [1];
(Formula Removed)
wherein, R is C1-C3 alkyl chain;
the process comprising;
(a) dehydrohalogenating 11-alkoxy-10-halo-10,11- dihydro-5H-dibenzo[b,f] azepine-5-carbonitrile compound of formula [XIX] in presence of an organic or inorganic base;
(Formula Removed)
wherein, R is C1-C3 alkyl chain and X is Cl, Br, I of F.
23. A process for preparing 10-alkoxy-5H-dibenz[b,f|azepine-5-carbonitrile compound of formula [XX] as claimed in claim 21 used in the preparation of 10-oxo-10,11-dihydro-5H-dibenz[b,f|azepine-5-carboxamide of formula [1];
(Formula Removed)
wherein, R is C1-C3 alkyl chain; the process comprising;
(a) cyanating 5H-dibenz[b,f]azepine compound of formula [VII]
(Formula Removed)
with a suitable cyanating agent to obtain 5H-dibenz[b,f]azepine-5-carbonitrile of formula [VIII]
(Formula Removed)
(b) alkoxyhalogenating the 5H-dibenz[b,f]azepine-5-carbonitrile of
formula [VIII] in presence of halogenating agent to obtain 11-alkoxy-10-halo-
10,11-dihydro-5H-dibenzo[b,f] azepine-5-carbonitrile compound of formula
[XIX];
wherein, R is C1-C3 alkyl chain and X is Cl, Br, I or F; and
(c) dehydrohalogenating 11-alkoxy-10-halo-10,11- dihydro-5H-
dibenzo[b,f] azepine-5-carbonitrile compound of formula [XIX] in presence of
an organic or inorganic base to obtain the intermediate, 10-alkoxy-5H-
dibenz[b,f]azepine-5-carbonitrile compound of formula [XX].
24. A process for preparing 10-alkoxy-5H-dibenz[b,f]azepine-5-carbonitrile of formula [XX] as claimed in claim 21 used in the preparation of 10-oxo-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide of formula [1];
(Formula Removed)
wherein, R is C1-C3 alkyl chain; the process comprising;
(a) dehydrating 5H-dibenz[b,f| azepine -5-carboxamide compound of formula [V]
(Formula Removed)
with a suitable dehydrating agent to obtain 5H-dibenz[b,f]azepine-5-carbonitrile of formula [VIII]
(Formula Removed)
(b) alkoxyhalogenating the 5H-dibenz[b,f]azepine-5-carbonitrile of
formula [VIII] in presence of halogenating agent to obtain 11-alkoxy-10-
halo-10,11-dihydro-5H-dibenzo[b,f] azepine-5-carbonitrile compound of
formula [XIX];
(Formula Removed)
wherein, R is C1-C3 alkyl chain and X is Cl, Br, I or F; and
(c) dehydrohalogenating 11-alkoxy-10-halo-10,11- dihydro-5H-
dibenzo[b,f] azepine-5-carbonitrile compound of formula [XIX] in presence of
an organic or inorganic base to obtain the intermediate, 10-alkoxy-5H-
dibenz[b,f]azepine-5-carbonitrile compound of formula [XX].
25. The process as claimed in any of claims 22, 23 or 24, wherein the organic base is selected from diethylamine, triethylamine, pyridine, l,8-diazabicyclo[2.2.2]octane, 1,5-diazabicyclo[4.3.0]non-5-ene, l,8-diazabicyclo[5.4.0]undec-7-ene, N-methyl morpholine, N-methylpiperidine, tetramethylguanidine alone or a mixture thereof.
26. The process as claimed in claims 22, 23 or 24, wherein the inorganic base is selected from alkali or alkaline earth metal alkoxides, hydroxides, carbonates bicarbonates.
27. The process as claimed in claims 22, 23 or 24, wherein the inorganic base is preferably selected from lithium, sodium, potassium, calcium or magnesium.
28. The process as claimed in claim 23 or 24, wherein said halogenating agent is selected from the group comprising 1,3-dihalo-dimethylhydantoin, N-halosuccinimide, N-haloacetamide or 1,3-haloisocyanuric acid alone or in combination thereof.
29. The process as claimed in any of claims 23 or 24, wherein the alkoxyhalogenation reaction is carried out in presence of an organic solvent.
30. The process as claimed in claim 29, wherein the organic solvent is selected from lower alcohols.
31. The process as claimed in claim 24, wherein said dehydrating agent is selected from group comprising P2O5 or POCI3 or SOCI2 or a mixture thereof

Documents:

1688-DEL-2006-Claims-(11-06-2012).pdf

1688-DEL-2006-Claims-(12-12-2011).pdf

1688-DEL-2006-Correspondence Others-(11-06-2012).pdf

1688-DEL-2006-Correspondence Others-(12-12-2011).pdf

1688-del-2006-correspondence-others.pdf

1688-del-2006-description (provisional).pdf

1688-DEL-2006-Form-1-(11-06-2012).pdf

1688-DEL-2006-Form-1-(12-12-2011).pdf

1688-del-2006-form-1.pdf

1688-DEL-2006-Form-2-(12-12-2011).pdf

1688-del-2006-form-2.pdf

1688-del-2006-form-26.pdf

1688-DEL-2006-Form-3-(12-12-2011).pdf

1688-del-2006-form-3.pdf

1688-DEL-2006-Form-5-(12-12-2011).pdf

1688-del-2006-form-5.pdf

1688-DEL-2006-GPA-(12-12-2011).pdf

1688-DEL-2006-Petition-137-(12-12-2011).pdf


Patent Number 255022
Indian Patent Application Number 1688/DEL/2006
PG Journal Number 03/2013
Publication Date 18-Jan-2013
Grant Date 15-Jan-2013
Date of Filing 24-Jul-2006
Name of Patentee JUBILANT ORGANOSYS LIMITED
Applicant Address PLOT 1A, SECTOR 16 A NOIDA-201301, UP, INDIA
Inventors:
# Inventor's Name Inventor's Address
1 SINGH HARNAM JUBILANT ORGANOSYS LIMITED, C-26, SECTOR 59, NOIDA-201301, UTTAR PRADESH, INDIA
2 GUPTA NITIN JUBILANT ORGANOSYS LIMITED, C-26, SECTOR 59, NOIDA-201301, UTTAR PRADESH, INDIA
3 KUMAR PRAMOD JUBILANT ORGANOSYS LIMITED, C-26, SECTOR 59, NOIDA-201301, UTTAR PRADESH, INDIA
4 DUBEY SUSHIL KUMAR JUBILANT ORGANOSYS LIMITED, C-26, SECTOR 59, NOIDA-201301, UTTAR PRADESH, INDIA
PCT International Classification Number C07D223/26
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA