Title of Invention	"AN IMPROVED PROCESS FOR THE PREPARATION OF N - (2,3 -DIHYDROBENZO [1,4] DIOXIN - 2 -CARBONYL ) PIPERAZINE"
Abstract	A process for the preparation of N-{2,3-Dihydrobenzo[1,4]dioxin-2-carbonyl) peiperazine which comprises heating a reaction mixture of 2,3-dihydrobenzo[1,4]dioxln-2-carboxylate and piperazine with a molar ratio of carboxytate to piperazine in the range of 1:2 to 2:1, under nitrogen atmosphere, at a temperature In the range of 70-90°C for a period of 3-15 hours, cooling the above said reaction mixture to a temperature of 25-30°C and dissolving it in chloroform followed by washing with saturated sodium bicarbonate solution and water respectively, acidifying the organic layer by 10% HCI to a pH ranging between 1 to 4, separating the organic layer and washing the aqueous layer with chloroform, basifying the aqueous layer with sodium bi-carbonate to a pH ranging between 7 to 9 followed by extracting with chloroform and evaporating the chloroform to obtain the final desired product in amorphous solid form.

Title of Invention

"AN IMPROVED PROCESS FOR THE PREPARATION OF N - (2,3 -DIHYDROBENZO [1,4] DIOXIN - 2 -CARBONYL ) PIPERAZINE"

Abstract

A process for the preparation of N-{2,3-Dihydrobenzo[1,4]dioxin-2-carbonyl) peiperazine which comprises heating a reaction mixture of 2,3-dihydrobenzo[1,4]dioxln-2-carboxylate and piperazine with a molar ratio of carboxytate to piperazine in the range of 1:2 to 2:1, under nitrogen atmosphere, at a temperature In the range of 70-90°C for a period of 3-15 hours, cooling the above said reaction mixture to a temperature of 25-30°C and dissolving it in chloroform followed by washing with saturated sodium bicarbonate solution and water respectively, acidifying the organic layer by 10% HCI to a pH ranging between 1 to 4, separating the organic layer and washing the aqueous layer with chloroform, basifying the aqueous layer with sodium bi-carbonate to a pH ranging between 7 to 9 followed by extracting with chloroform and evaporating the chloroform to obtain the final desired product in amorphous solid form.

Full Text	The present invention relates to a process for the preparation of N-(2,3-Dihydrobenzo[l ,4]dioxin-2-carbonyl) piperazine. N-(2,3-Dihydrobenzo[l,4]dioxin-2-carbonyl) piperazine is an important intermediate for the preparation of an anti-hypertensive drug viz., doxazocin. Doxazocin is prepared by reaction of N-(2,3-Dihydrobenzo[l,4]dioxin-2-carbonyl)piperazine with 4-amino-2-chloro-6,7-dimethoxy quinazoline[J. Med. Chem. 1987, 30(1), 49]. However, it was observed that the product obtained by this condensation contained bis-amide as impurity. It makes the product unsuitable for pharmaceutical use as doxazocin base prepared by basification, on analysis showed purity of 91-94% only. Further purification of the base was very difficult due to its polymorphic nature. Large number of references are available mostly of patents (US patents 6,140,334; 6,133,269; 6,130,218) in which doxazocin base has been subjected to tedious purification procedures consisting of four to five steps in order to obtain pure doxazocin of pharmaceutical grade. Pharmaceutical industry requires pure doxazocin (99.99%) for processing into solid dosage form. In our attempts to prepare pure doxazocin , we found that the purity and crystalline nature of doxazocin were dependent on the purity of N-(2,3-Dihydrobenzo[l,4]dioxin-2-carbonyl) piperazine that was used for the condensation. While it was easy to prepare 4-amino-2-chloro-6,7-dimethoxy quinazoline in high yield and purity, the preparation of N-(2,3-Dihydrobenzo[l,4]dioxin-2-carbonyl)piperazine posed several problems due to its contamination with the bis-amide impurity. It is glassy and difficult to work with. It is essential to evolve a method for the preparation of pure amide not contaminated with bis-amide. N-(2,3-Dihydrobenzo[l,4]dioxin-2-carbonyl)piperazine is a condensation product of ethyl 2,3-Dihydrobenzo[l,4]dioxin-2-carboxylate and piperazine[eq-l]. N-Acyl alkylenediamines were earlier prepared by the monoamidation of alkylenediamines with acid chlorides. The reaction requires the masking of diamines as monoacetates or hydrogen halides [J. Med. Chem.,1997, 20, 146]. The procedure is tedious and requires i) saponification of ester ii) treatment of the resulting acid with thionyl chloride to give the acid chloride and iii) amidation with piperazine hydrobromide in methanol. There is also one report of the synthesis of N-Acyl alkylenediamines(94% yield) by direct monoamidation of esters[J. Org. Chem., 1998, 63, 10015]. In this procedure, ethyl 2,3-dihydrobenzo[l,4]dioxin-2- carboxylatt and piperazine were heated under reflux for 3h. The reaction mixture was partitioned between CHCl3 and saturated aq, NaHCO3. The organic layer was washed, dried and concentrated. However, N-(2,3-Dlhydrobenzc{1.4]dioxin-2-oarbonyl)piperazine prepared by the above method when coupled with 4-amino-2-chloro'6,7-dimethoxy quinezoline gave a product, which on subsequent basification, gave doxazocin base with 92-95% purity. In view of the above, it is necessary to develop an improved process for the preparation of high purity N-(2,3-Dihydrobenzo[1,4]dioxin-2-carbonyl)piperazine without contamination with bid-amide. The main objective of the present invention is to provide a process for the preparation of high purity N-(2,3-Dlhydrobenzo[1,4]dloxln-2-carbonyl)piperazine of . Formula-1. Another object of the present invention is to provide N-(2,3-Dlhydrobenzo[l,4]dioxin-2-carbonyl)p9lperazlne free from bis-amide and other impurities by simple acid base work-up procedure. Accord ngly, the present invention provides a process for the preparation of N-(2,3-Dihydrobenzo[1,4]dioxin-2-carbonyl) pelperazlne which comprises heating a reaction mixture of 2,3-dihydrobenzo[1,4]dioxin-2-carboxylate and piperazine with a molar ratio of carboxylate to piperazine in the range of 1:2 to 2:1, under nitrogen atmosphere, at a temperature in the range of 70-90oC for a period of 3-15 hours, cooling the above said reaction mixture to a temperature of 25-30°C and dissolving it in chloroform followed by washing with saturated sodium bicarbonate solution and water respectively, acidifying the organic layer by 10% HCI to a pH ranging between 1 to 4, separating the organic layer and washing the aqueous layer with chloroform, baslfying the aqueous layer with sodium bl-carbonate to a pH ranging between 7 to 9 followed by extracting with chloroform and evaporating the chloroform to obtain the final desired product in amorphous solid form. In an embodiment of the present invention the reaction mixture is heated for a period preferably in the range of 5-12 hours. In yet another embodiment the temperature used In heating reaction mixture is preferably in the range of 75-80°C. In still another embodiment the purity of the compound N-(2,3-Dihydrobenzo[1,4]dioxln-2-carbonyl) piperazine obtain is in the range of 99.3-99.9%. In the improved process for the preparation of N-(2,3-dihydrobenzo[1,4]dioxin-2-carbonyl) piperazine heating a reaction mixture of 2,3-dlhydrobenzo[1,4]dioxin-2-carboxylate and piperazine with a molar ratio of carboxyiate to piperazine in the range of 1:2 to 2:1, under nitrogen atmosphere, at a temperature in the range of 70-90°C for a period of 3-15 hours, cooling the above said reaction mixture to a temperature of 25-30"C and dissolving it in chloroform followed by washing with saturated sodium bicarbonate solution and water respectively, acidifying the organic layer by 10% HCI to a pH ranging between 1 to 4, separating the organic layer and washing the aqueous layer with chloroform, basifying the aqueous layer with sodium bi-carbonate to a pH ranging between 7 to 9 followed by extracting with chloroform and evaporating the chloroform to obtain the final desired product In amorphous solid form. The following examples are given by way of illustration of the present invention and therefore should not be construed to limit the scope of the present invention. Example-1 Piperazine (101.3g, 1.175 moles) and ethyl 2-carboethoxy-i,4-benzodioxalane (200g, 0.96 moles) were taken Into a round bottom flask provided with a stirrer, thermowell, and distillation setup. The reaction mixture was heated for 4h to reach an Internal temperature of about 75°C while stirring. It was cooled to room temperature, dissolved in chloroform (200 ml) and washed with saturated sodium bicarbonate solution (1x150 ml) followed by water wash (3x150 ml). The organic layer was acidified to pH 2 with 10% HCI (600 ml). The organic layer was separated and aqueous layer washed with chloroform (3x100 ml). The aqueous portion was baaified with solid sodium bicarbonate to pH 8 and was extracted with chloroform (5x150 ml). The chloroform layer was evaporated to yield amorphous solid powder (145g, 61% yield), purity 99.9%. Example-2 Piperazine (10,13g, 0.1175 moles) and ethyl 2-carboethoxy-1,4-benzodioxalane (20g, 0.096 moles) were taken into a round bottom flask provided with a stirrer, thermowell and distillation setup. The reaction mixture was heated for 10h to reach an internal temperature of about 75°C while stirring. It was cooled to room temperature, dissolved in chloroform and washed with saturated sodium bicarbonate solution followed by water. The organic layer was acidified to pH 2 with 10% HC1. The organic layer was separated and aqueous layer washed with chloroform. This aqueous portion was basified with solid sodium bicarbonate to pH 8 and was extracted with chloroform. The chloroform layer was evaporated to yield amorphous solid powder (21.67g, 89.5% yield) purity 99.9%. Example-3 Piperazine (8.2g, 0.096 moles) and ethyl 2-carboethoxy-l,4-benzodioxalane (20g, 0.096moles) were taken into a round bottom flask provided with a stirrer, thermowell and distillation setup. The reaction mixture is heated for 10h to reach an internal temperature of about 75 °C while stirring. It was cooled to room temperature, dissolved in chloroform and washed with saturated sodium bicarbonate solution followed by water. The organic layer was acidified to pH 2 with 10% HC1. The organic layer was separated and aqueous layer washed with chloroform. This aqueous portion was basified with solid sodium bicarbonate to pH 8 and was extracted with chloroform. The chloroform layer was evaporated to yield amorphous solid powder (7.14g, 30 % yield), purity 99.3. Example-4 piperazine (12.4g, 0,144 moles) and ethyl 2-carboethoxy-l,4-benzodioxalane (20g, 0.096 moles were taken into a round bottom flask provided with a stirrer, thermowell and distillation setup. The reaction mixture was heated for 10h to reach an internal temperature of about 75°C while stirring. It was cooled to room temperature, dissolved in chloroform and washed with saturated sodium bicarbonate solution followed by water. The organic layer was acidified to pH 2 with 10% HC1. The organic layer was separated and aqueous layer washed with chloroform. This aqueous portion was basified with sodium bicarbonate to pH 8 and was extracted with chloroform. The chloroform layer was evaporated to yield amorphous solid powder (10.7g, 45 % yield), purity 99.6%. Example-5 Into a round bottom flask provided with a stirrer, thermowell and distillation set up were taken piperazine (5.5g, 0.064 moles) and ethyl 2-carboethoxy-1,4-benzodioxalane (20g, 0.096moles). The reaction mixture is heated for 10h to reach an internal temperature of about 75°C while stirring. It was cooled to room temperature, dissolved in chloroform and washed with saturated sodium bicarbonate solution followed by water .The organic layer was acidified to pH 2 with 10% HC1. The organic layer was separated and aqueous layer washed with chloroform. This aqueous portion was basified with solid sodium bicarbonate to PH 8 and was extracted with chloroform. The chloroform layer was evaporated to yield amorphous solid powder (7.5g,31.5%yield), purity 99.45%. The main advantages of the present invention are: 1. it is a very convenient process in which me bis-amkle easily seperaled by acid treatment of the reaction mixture of N-(2,3-Dihydrobcnzo[l,4]dioxin-2-carbonyl)piperazine. 2. N-(2,3-Dihydrobenzo[l,4]dioxin-2-carbonyl)piperazine prepared by this method when coupled with 4-amino-2-chloro-6,7-dimethoxy quinazoline, gives the HC1 salt which on basification affords 99.99% pure doxazocin base. 3. The doxazocin base thus obtained can be used without any further purification to get doxzocin mesylate with purity (99.99%) as required by the pharmaceutical industry. We claim: 1. A process for the preparation of N-(2,3-Dihydrobenzo[1,4]dioxin-2-carbonyl) peiperazine which comprises heating a reaction mixture of 2,3- dihydrobenzo[l,4]dioxin-2-carboxylate and piperazine with a molar ratio of carboxylate to piperazine in the range of 1:2 to 2:1, under nitrogen atmosphere, at a temperature In the range of 70-90°C for a period of 3-15 hours, cooling the above said reaction mixture to a temperature of 25-30°C and dissolving it in chloroform followed by washing with saturated sodium bicarbonate solution and water respectively, acidifying the organic layer by 10% HCI to a pH ranging between 1 to 4, separating the organic layer and washing the aqueous layer with chloroform, basifying the aqueous layer with sodium bi-carbonate to a pH ranging between 7 to 9 followed by extracting with chloroform and evaporating the chloroform to obtain the final desired product in amorphous solid form. 2. A process as claimed in claim 1 wherein the reaction mixture Is heated for a period preferably In the range of 5-12 hours. 3. A process as claimed In claims 1-2 wherein the reaction temperature used is preferably in the range of 75-80°C. 4. A process for the preparation of N-(2,3-Dihydrobenzo[1,4]dioxin-2-carbonyl) peiperazine substantially as herein described with reference to the examples and drawing accompanying this specification,

Full Text

The present invention relates to a process for the preparation of N-(2,3-Dihydrobenzo[l ,4]dioxin-2-carbonyl) piperazine.
N-(2,3-Dihydrobenzo[l,4]dioxin-2-carbonyl) piperazine is an important intermediate for the preparation of an anti-hypertensive drug viz., doxazocin. Doxazocin is prepared by reaction of N-(2,3-Dihydrobenzo[l,4]dioxin-2-carbonyl)piperazine with 4-amino-2-chloro-6,7-dimethoxy quinazoline[J. Med. Chem. 1987, 30(1), 49]. However, it was observed that the product obtained by this condensation contained bis-amide as impurity. It makes the product unsuitable for pharmaceutical use as doxazocin base prepared by basification, on analysis showed purity of 91-94% only. Further purification of the base was very difficult due to its polymorphic nature. Large number of references are available mostly of patents (US patents 6,140,334; 6,133,269; 6,130,218) in which doxazocin base has been subjected to tedious purification procedures consisting of four to five steps in order to obtain pure doxazocin of pharmaceutical grade.
Pharmaceutical industry requires pure doxazocin (99.99%) for processing into solid dosage form. In our attempts to prepare pure doxazocin , we found that the purity and crystalline nature of doxazocin were dependent on the purity of N-(2,3-Dihydrobenzo[l,4]dioxin-2-carbonyl) piperazine that was used for the condensation. While it was easy to prepare 4-amino-2-chloro-6,7-dimethoxy quinazoline in high yield and purity, the preparation of N-(2,3-Dihydrobenzo[l,4]dioxin-2-carbonyl)piperazine posed several problems due to its contamination with the bis-amide impurity. It is glassy and difficult to work with. It is essential to evolve a method for the preparation of pure amide not contaminated with bis-amide.
N-(2,3-Dihydrobenzo[l,4]dioxin-2-carbonyl)piperazine is a condensation product of ethyl 2,3-Dihydrobenzo[l,4]dioxin-2-carboxylate and piperazine[eq-l]. N-Acyl alkylenediamines were earlier prepared by the monoamidation of alkylenediamines with acid chlorides. The reaction requires the masking of diamines as monoacetates or hydrogen halides [J. Med. Chem.,1997, 20, 146]. The procedure is tedious and requires i) saponification of ester ii) treatment of the resulting acid with thionyl chloride to give the acid chloride and iii) amidation with piperazine hydrobromide in methanol. There is also one report of the synthesis of N-Acyl alkylenediamines(94% yield) by direct monoamidation of esters[J. Org. Chem., 1998, 63, 10015]. In this procedure, ethyl 2,3-dihydrobenzo[l,4]dioxin-2-

carboxylatt and piperazine were heated under reflux for 3h. The reaction mixture was partitioned between CHCl3 and saturated aq, NaHCO3. The organic layer was washed, dried and concentrated. However, N-(2,3-Dlhydrobenzc{1.4]dioxin-2-oarbonyl)piperazine prepared by the above method when coupled with 4-amino-2-chloro'6,7-dimethoxy quinezoline gave a product, which on subsequent basification, gave doxazocin base with 92-95% purity. In view of the above, it is necessary to develop an improved process for the preparation of high purity N-(2,3-Dihydrobenzo[1,4]dioxin-2-carbonyl)piperazine without contamination with bid-amide.
The main objective of the present invention is to provide a process for the preparation of high purity N-(2,3-Dlhydrobenzo[1,4]dloxln-2-carbonyl)piperazine of . Formula-1.
Another object of the present invention is to provide N-(2,3-Dlhydrobenzo[l,4]dioxin-2-carbonyl)p9lperazlne free from bis-amide and other impurities by simple acid base work-up procedure.
Accord ngly, the present invention provides a process for the preparation of N-(2,3-Dihydrobenzo[1,4]dioxin-2-carbonyl) pelperazlne which comprises heating a reaction mixture of 2,3-dihydrobenzo[1,4]dioxin-2-carboxylate and piperazine with a molar ratio of carboxylate to piperazine in the range of 1:2 to 2:1, under nitrogen atmosphere, at a temperature in the range of 70-90oC for a period of 3-15 hours, cooling the above said reaction mixture to a temperature of 25-30°C and dissolving it in chloroform followed by washing with saturated sodium bicarbonate solution and water respectively, acidifying the organic layer by 10% HCI to a pH ranging between 1 to 4, separating the organic layer and washing the aqueous layer with chloroform, baslfying the aqueous layer with sodium bl-carbonate to a pH ranging between 7 to 9 followed by extracting with chloroform and evaporating the chloroform to obtain the final desired product in amorphous solid form.
In an embodiment of the present invention the reaction mixture is heated for a period preferably in the range of 5-12 hours.
In yet another embodiment the temperature used In heating reaction mixture is preferably in the range of 75-80°C.
In still another embodiment the purity of the compound N-(2,3-Dihydrobenzo[1,4]dioxln-2-carbonyl) piperazine obtain is in the range of 99.3-99.9%.
In the improved process for the preparation of N-(2,3-dihydrobenzo[1,4]dioxin-2-carbonyl) piperazine heating a reaction mixture of 2,3-dlhydrobenzo[1,4]dioxin-2-carboxylate and piperazine with a molar ratio of carboxyiate to piperazine in the range of 1:2 to 2:1, under nitrogen atmosphere, at a temperature in the range of 70-90°C for a period of 3-15 hours, cooling the above said reaction mixture to a temperature of 25-30"C and dissolving it in chloroform followed by washing with saturated sodium bicarbonate solution and water respectively, acidifying the organic layer by 10% HCI to a pH ranging between 1 to 4, separating the organic layer and washing the aqueous layer with chloroform, basifying the aqueous layer with sodium bi-carbonate to a pH ranging between 7 to 9 followed by extracting with chloroform and evaporating the chloroform to obtain the final desired product In amorphous solid form.
The following examples are given by way of illustration of the present invention and therefore should not be construed to limit the scope of the present invention.
Example-1
Piperazine (101.3g, 1.175 moles) and ethyl 2-carboethoxy-i,4-benzodioxalane (200g, 0.96 moles) were taken Into a round bottom flask provided with a stirrer, thermowell, and distillation setup. The reaction mixture was heated for 4h to reach an Internal temperature of about 75°C while stirring. It was cooled to room temperature, dissolved in chloroform (200 ml) and washed with saturated sodium bicarbonate solution (1x150 ml) followed by water wash (3x150 ml). The organic layer was acidified to pH 2 with 10% HCI (600 ml). The organic layer was separated and aqueous layer washed with chloroform (3x100 ml). The aqueous portion was baaified with solid sodium bicarbonate to pH 8 and was extracted with chloroform (5x150 ml). The chloroform layer was evaporated to yield amorphous solid powder (145g, 61% yield),
purity 99.9%.
Example-2
Piperazine (10,13g, 0.1175 moles) and ethyl 2-carboethoxy-1,4-benzodioxalane (20g, 0.096 moles) were taken into a round bottom flask provided with a stirrer, thermowell and distillation setup. The reaction mixture was heated for 10h to reach an internal temperature of about 75°C while stirring. It was cooled to room temperature, dissolved in chloroform and washed with saturated sodium bicarbonate solution followed by water. The organic layer
was acidified to pH 2 with 10% HC1. The organic layer was separated and aqueous layer washed with chloroform. This aqueous portion was basified with solid sodium bicarbonate to pH 8 and was extracted with chloroform. The chloroform layer was evaporated to yield amorphous solid powder (21.67g, 89.5% yield) purity 99.9%.
Example-3
Piperazine (8.2g, 0.096 moles) and ethyl 2-carboethoxy-l,4-benzodioxalane (20g, 0.096moles) were taken into a round bottom flask provided with a stirrer, thermowell and distillation setup. The reaction mixture is heated for 10h to reach an internal temperature of about 75 °C while stirring. It was cooled to room temperature, dissolved in chloroform and washed with saturated sodium bicarbonate solution followed by water. The organic layer was acidified to pH 2 with 10% HC1. The organic layer was separated and aqueous layer washed with chloroform. This aqueous portion was basified with solid sodium bicarbonate to pH 8 and was extracted with chloroform. The chloroform layer was evaporated to yield amorphous solid powder (7.14g, 30 % yield), purity 99.3.
Example-4
piperazine (12.4g, 0,144 moles) and ethyl 2-carboethoxy-l,4-benzodioxalane (20g, 0.096 moles were taken into a round bottom flask provided with a stirrer, thermowell and distillation setup. The reaction mixture was heated for 10h to reach an internal temperature of about 75°C while stirring. It was cooled to room temperature, dissolved in chloroform and washed with saturated sodium bicarbonate solution followed by water. The organic layer was acidified to pH 2 with 10% HC1. The organic layer was separated and aqueous layer washed with chloroform. This aqueous portion was basified with sodium bicarbonate to pH 8 and was extracted with chloroform. The chloroform layer was evaporated to yield amorphous solid powder (10.7g, 45 % yield), purity 99.6%.
Example-5
Into a round bottom flask provided with a stirrer, thermowell and distillation set up were taken piperazine (5.5g, 0.064 moles) and ethyl 2-carboethoxy-1,4-benzodioxalane (20g, 0.096moles). The reaction mixture is heated for 10h to reach an internal temperature of about 75°C while stirring. It was cooled to room temperature, dissolved in chloroform and washed with saturated sodium bicarbonate solution followed by water .The organic layer was acidified to pH 2 with 10% HC1. The organic layer was separated and aqueous layer washed with chloroform. This aqueous portion was basified with solid sodium bicarbonate to PH 8 and was extracted with chloroform. The chloroform layer was evaporated to yield amorphous solid powder (7.5g,31.5%yield), purity 99.45%.
The main advantages of the present invention are:
1. it is a very convenient process in which me bis-amkle easily seperaled by acid treatment
of the reaction mixture of N-(2,3-Dihydrobcnzo[l,4]dioxin-2-carbonyl)piperazine.
2. N-(2,3-Dihydrobenzo[l,4]dioxin-2-carbonyl)piperazine prepared by this method when
coupled with 4-amino-2-chloro-6,7-dimethoxy quinazoline, gives the HC1 salt which on
basification affords 99.99% pure doxazocin base.
3. The doxazocin base thus obtained can be used without any further purification to get
doxzocin mesylate with purity (99.99%) as required by the pharmaceutical industry.

We claim:
1. A process for the preparation of N-(2,3-Dihydrobenzo[1,4]dioxin-2-carbonyl)
peiperazine which comprises heating a reaction mixture of 2,3-
dihydrobenzo[l,4]dioxin-2-carboxylate and piperazine with a molar ratio of
carboxylate to piperazine in the range of 1:2 to 2:1, under nitrogen atmosphere,
at a temperature In the range of 70-90°C for a period of 3-15 hours, cooling the
above said reaction mixture to a temperature of 25-30°C and dissolving it in
chloroform followed by washing with saturated sodium bicarbonate solution and
water respectively, acidifying the organic layer by 10% HCI to a pH ranging
between 1 to 4, separating the organic layer and washing the aqueous layer with
chloroform, basifying the aqueous layer with sodium bi-carbonate to a pH
ranging between 7 to 9 followed by extracting with chloroform and evaporating
the chloroform to obtain the final desired product in amorphous solid form.
2. A process as claimed in claim 1 wherein the reaction mixture Is heated for a
period preferably In the range of 5-12 hours.
3. A process as claimed In claims 1-2 wherein the reaction temperature used is
preferably in the range of 75-80°C.
4. A process for the preparation of N-(2,3-Dihydrobenzo[1,4]dioxin-2-carbonyl)
peiperazine substantially as herein described with reference to the examples
and drawing accompanying this specification,

Documents:

995-del-2002-abstract.pdf

995-del-2002-claims.pdf

995-del-2002-correspondence-others.pdf

995-del-2002-correspondence-po.pdf

995-del-2002-description (complete).pdf

995-del-2002-drawings.pdf

995-del-2002-form-1.pdf

995-del-2002-form-2.pdf

995-del-2002-form-3.pdf

995-del-2002-form-4.pdf

995-del-2002-petition-138.pdf

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Patent Number

199846

Indian Patent Application Number

995/DEL/2002

PG Journal Number

40/2007

Publication Date

05-Oct-2007

Grant Date

24-Nov-2006

Date of Filing

30-Sep-2002

Name of Patentee

COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH

Applicant Address

RAFI MARG, NEW DELHI - 110001, INDIA.

Inventors:

#	Inventor's Name	Inventor's Address
1	GULLAPALLI KUMARASWAMY	INDIAN INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD 500007, A.P. INDIA.
2	MUDIGANTI NAGA VENKATA SASTRY	INDIAN INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD 500007, A.P. INDIA.
3	MALLADI PARDHASARDHI	INDIAN INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD 500007, A.P. INDIA.
4	ARUN KANTI DAS	INDIAN INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD 500007, A.P. INDIA.
5	NIVEDITA JENA	INDIAN INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD 500007, A.P. INDIA.
6	CHEMBUMKULAM KAMALAKSHYAMMA SNEHALATHA NAIR	INDIAN INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD 500007, A.P. INDIA.

PCT International Classification Number

A61K 31/00

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA