WO2004058719A1 - A process for preparing benzocyclohetapyridin-11-ones - Google Patents

A process for preparing benzocyclohetapyridin-11-ones Download PDF

Info

Publication number
WO2004058719A1
WO2004058719A1 PCT/IN2002/000246 IN0200246W WO2004058719A1 WO 2004058719 A1 WO2004058719 A1 WO 2004058719A1 IN 0200246 W IN0200246 W IN 0200246W WO 2004058719 A1 WO2004058719 A1 WO 2004058719A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
formula
formula iii
range
anhydrous
Prior art date
Application number
PCT/IN2002/000246
Other languages
French (fr)
Inventor
Bhavin R. Sonak
Satish Champaklal Manakiwala
Virendra Kumar Agarwal
Kanwal Pandita
Pankaj Ramanbhai Patel
Original Assignee
Cadila Healthcare Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cadila Healthcare Limited filed Critical Cadila Healthcare Limited
Priority to AU2002368506A priority Critical patent/AU2002368506A1/en
Priority to PCT/IN2002/000246 priority patent/WO2004058719A1/en
Publication of WO2004058719A1 publication Critical patent/WO2004058719A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/04—Ortho- or peri-condensed ring systems
    • C07D221/06—Ring systems of three rings
    • C07D221/16—Ring systems of three rings containing carbocyclic rings other than six-membered

Definitions

  • the present invention relates to a process for the preparation of benzocyclohetapyridin-11-ones compounds.
  • Background of the invention :
  • the present invention provides a new process for preparing benzocyclohepta pyridine- 11-ones.
  • Benzocyclohepta pyridine-11-ones compounds are well known in the art and there are several teachings in the prior art for the preparation of this compound.
  • Benzocyclohepta pyridine-11-ones typically have the formula (III):
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are independently selected from the groups consisting of hydrogen, halogen, Ci to C 6 -alkyl, d-C6 alkoxy.
  • alkyl means straight or branched hydrocarbon chains of 1 to 10 carbon atoms, preferably 1 to 6 carbon atoms, optionally substituted by one or more substituents selected from Ci to C 6 alkoxy, halo, or CF 3 .
  • Alkoxy means a group having the formula -O-alkyl.
  • Halo refers to fluorine, chlorine or bromine.
  • FPT farnesyl protein transferase
  • amide derivative of the acid is cyclised by P O 5 / CF 3 SO 3 H, POCl 3 / CF 3 SO 3 H, CF 3 SO 3 H or HF / BF 3 .
  • the process suffers the disadvantage of difficult operation and low yield.
  • C ⁇ 1151987 discloses the preparation of III by cyclization of 3-[2-(3,8-dihalo-phenyl) ethyl-2-pyridine by Bu ⁇ Li or i-Pr ⁇ Li at - 100°C to 20°C.
  • the starting material used therein is difficult to prepare, moreover use of expensive and hazardous lithium compounds restricts the scope of the process for commercial use.
  • the present invention discloses herein a new process for the preparation of benzocycloheptapyridin-11-ones having formula (III) by intramolecular cyclization of compounds having the formula (I) with anhydrous hydrofluoric acid and boron trifluoride, hydrolyzing the resulting corresponding imino compound having formula (II) to the corresponding tricyclic ketone as shown in the scheme - 2.
  • the present invention provides a process for the preparation of benzolycloheptapyridin-11-ones of the general formula III
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are independently selected from one or more of the following groups: hydrogen, halogen, C1-C6 alkyl, CI - C6 alkoxy, which comprises a) reacting a compound of general formula (I),
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined above, with anhydrous HF/BF 3 at a temperature in the range of-100°C to -20°C, to produce a compound of formula (II),
  • said compound of formula I is reacted with said anhydrous HF/BF 3 at a temperature in the range of -60 to -75°C.
  • said hydrolysis is carried out by dumping the reaction product of said compound of formula II and said anhydrous HF/BF 3 in ice-water, stirring the reaction mass for 20 - 80 hours at -50 °C to 70 °C to hydrolyse the compound of formula III.
  • said compound of formula III is isolated by collecting the salt of said compound of formula III with tetrafluoroboric acid, stirring the salt with water and adjusting the pH in the range of 6 to 10 with alkali to liberate said compound of formula III, extracting said compound of Formula III with solvent extraction and distillation and recovering said compound of formula III in pure form by centrifugation and drying
  • said anhydrous HF is employed in an amount of 10 to 60 moles, preferably, 20 to 30 moles with respect to the compound I used.
  • said BF 3 is used in a molar ratio of 1 to 10 moles to that of compound I.
  • said BF 3 gas is passed in for a period ranging from 20 to 60 hours, more preferably, from 45 to 55 hours.
  • the temperature is maintained in the range of 20 to
  • the present invention seeks to provide an alternative method for the preparation of compounds having formula III from compounds having formula I comprising following steps: (1). intramolecular cyclization of compounds having the formula (I) with anhydrous hydrofluoric acid and boron trifluoride, and (2) hydrolyzing the resulting corresponding imino compound having formula (II) to the corresponding tricyclic ketone
  • compounds having formula I are dissolved in 10 - 60 moles preferably 20 -30 moles of hydrofluoric acid at -20° to -100°, preferably at -60 to -75°C. To this 1 - 10 moles, more preferably 4-5 moles of boron trifluoride is slowly passed at this temperature for 45 to 55 hours showing complete conversion of compound I to compound II (Scheme - 1).
  • reaction mass is dumped into ice-water. This is stirred for 20 to 50 hours, preferably 25 to 35 hours at -50 °C to 70° C, preferably at 25 to 35°C to compounds having formula - III (Scheme -1).
  • the solid thus obtained is tetrafluoroboric acid salt of compound of formula - III which is treated with base such as hydroxide or carbonates salts of lithium, sodium, potassium or ammonia.
  • Potassium carbonate is the most preferred base, thereby liberating compound of formula (III), which is extracted in non-polar solvent, which is selected from aromatic hydrocarbon such as benzene, toluene, xylene and alkyl halides such as methylene chloride, chloroform, ethylene dichloride, trichloroethane.
  • non-polar solvent which is selected from aromatic hydrocarbon such as benzene, toluene, xylene and alkyl halides such as methylene chloride, chloroform, ethylene dichloride, trichloroethane.
  • Toluene is the most preferred solvent for extraction. The solvent is removed by distillation at reduced pressure and the residue thus obtained is stirred with aliphatic hydrocarbon solvent, the solid is centrifuged and dried to get the pure compound having the formula III.
  • a solution of 30 kgs of (3-[2-(3-chlorophenyl)ethyl]-2-cyanopyridine) in 60 kg of anhydrous hydrofluoric acid is slowly passed through 40 kg of boron trifluoride at -60 °C to -75 °C in about 45 to 55 hours.
  • the reaction mass is then dumped over ice-water and stirred for 25 to 35 hours at 25 °C to 35°C.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

A process for the preparation of benzocydoheptapyridin-11-ones of the general formula (III) wherein R1, R2, R3, R4, R5, R6 and R7 are independently selected from one or more of the following groups: hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, which comprises a) reacting a compound of general formula (I), wherein R1, R2, R3, R4, R5, R6 and R7 are as defined above, with anhydrous HF/BF3 at a temperature in the range of -100°C to -20°C, to produce a compound of formula (II), wherein R1, R2 R3, R4, R5, R6 and R7 are as defined above; and hydrolysing it to compound of formula (III).

Description

A PROCESS FOR PREPARING BENZOCYCLOHETAPYREDIN-11-ONES Field of the invention:
The present invention relates to a process for the preparation of benzocyclohetapyridin-11-ones compounds. Background of the invention:
The present invention provides a new process for preparing benzocyclohepta pyridine- 11-ones. Benzocyclohepta pyridine-11-ones compounds are well known in the art and there are several teachings in the prior art for the preparation of this compound.
Benzocyclohepta pyridine-11-ones typically have the formula (III):
Figure imgf000002_0001
The substituents R1, R2, R3, R4, R5, R6 and R7 are independently selected from the groups consisting of hydrogen, halogen, Ci to C6-alkyl, d-C6 alkoxy. As used herein, the term "alkyl" means straight or branched hydrocarbon chains of 1 to 10 carbon atoms, preferably 1 to 6 carbon atoms, optionally substituted by one or more substituents selected from Ci to C6 alkoxy, halo, or CF3. "Alkoxy" means a group having the formula -O-alkyl. "Halo" refers to fluorine, chlorine or bromine.
These compounds are useful as intermediates in the preparation of antihistamines and as inhibitors of farnesyl protein transferase (FPT) especially loratadine and azatadine.
US 3326924, 4659716, 5998620, 6372909; WO 0005215, 0030589, 0179175; CN 1151987; J. Med. Chem. 34, 461-463 (1961); Bioorg. Med. Chem Lett 3, 1073-1078 (1993), which are herein incorporated by references describe various processes for the preparation of compounds having formula III. Similarly WO-0030589 also describes cyclization of compound (I) by CF3SO3H to compound III.
US 3326924 describes the preparation of compounds having the formula III as shown in the scheme I. SCHEME: 1
Figure imgf000003_0001
Main disadvantage of the process as disclosed therein is the formation of undesired isomeric product IN in substantial amount (Scheme - 2).
In an alternative method amide derivative of the acid is cyclised by P O5 / CF3SO3H, POCl3 / CF3SO3H, CF3SO3H or HF / BF3. The process suffers the disadvantage of difficult operation and low yield. Carboxylic acid derivatives (Scheme II, X = OH) is cyclised by polyphosphoric acid at 200°C. The process disclosed therein results in poor yield of the desired products of formula (III) with a lot of polymeric material formation, making the process unsuitable on commercial scale.
CΝ 1151987 discloses the preparation of III by cyclization of 3-[2-(3,8-dihalo-phenyl) ethyl-2-pyridine by BuΝLi or i-Pr ΝLi at - 100°C to 20°C. The starting material used therein is difficult to prepare, moreover use of expensive and hazardous lithium compounds restricts the scope of the process for commercial use.
US 4659716 describes the use of HF / BF3 for cyclization of (l-methyl-4-piperazinyl)-[3-[2- (3-chlorophenyl)ethyl]-2-pyridyl]methanone for preparation of corresponding benzocycloheptapyridinylidene piperidine derivative. The same methodology is employed for cyclization of compounds of formula I to get the desired compound of formula III (Scheme - Summary of the invention:
The present invention discloses herein a new process for the preparation of benzocycloheptapyridin-11-ones having formula (III) by intramolecular cyclization of compounds having the formula (I) with anhydrous hydrofluoric acid and boron trifluoride, hydrolyzing the resulting corresponding imino compound having formula (II) to the corresponding tricyclic ketone as shown in the scheme - 2.
SCHEME; 2
Figure imgf000004_0001
(III)
Accordingly, the present invention provides a process for the preparation of benzolycloheptapyridin-11-ones of the general formula III
Figure imgf000005_0001
wherein R1, R2, R3, R4, R5, R6 and R7 are independently selected from one or more of the following groups: hydrogen, halogen, C1-C6 alkyl, CI - C6 alkoxy, which comprises a) reacting a compound of general formula (I),
Figure imgf000005_0002
wherein R1, R2, R3, R4, R5, R6 and R7 are as defined above, with anhydrous HF/BF3 at a temperature in the range of-100°C to -20°C, to produce a compound of formula (II),
Figure imgf000005_0003
(H) wherein R1, R2, R3, R4, R5, R6 and R7 are as defined above; and b) hydrolysing said compound of formula II to obtain said compound of the general formula
III.
Preferably, said compound of formula I is reacted with said anhydrous HF/BF3 at a temperature in the range of -60 to -75°C. Preferably, said hydrolysis is carried out by dumping the reaction product of said compound of formula II and said anhydrous HF/BF3 in ice-water, stirring the reaction mass for 20 - 80 hours at -50 °C to 70 °C to hydrolyse the compound of formula III.
In a preferred embodiment, said compound of formula III is isolated by collecting the salt of said compound of formula III with tetrafluoroboric acid, stirring the salt with water and adjusting the pH in the range of 6 to 10 with alkali to liberate said compound of formula III, extracting said compound of Formula III with solvent extraction and distillation and recovering said compound of formula III in pure form by centrifugation and drying
In a preferred embodiment, said anhydrous HF is employed in an amount of 10 to 60 moles, preferably, 20 to 30 moles with respect to the compound I used.
In an embodiment of the invention, said BF3 is used in a molar ratio of 1 to 10 moles to that of compound I.
In another preferred embodiment, said BF3 gas is passed in for a period ranging from 20 to 60 hours, more preferably, from 45 to 55 hours. Preferably, during hydrolysis the temperature is maintained in the range of 20 to
40°C. Detailed description of the invention:
The present invention seeks to provide an alternative method for the preparation of compounds having formula III from compounds having formula I comprising following steps: (1). intramolecular cyclization of compounds having the formula (I) with anhydrous hydrofluoric acid and boron trifluoride, and (2) hydrolyzing the resulting corresponding imino compound having formula (II) to the corresponding tricyclic ketone
In a preferred embodiment of the invention, compounds having formula I are dissolved in 10 - 60 moles preferably 20 -30 moles of hydrofluoric acid at -20° to -100°, preferably at -60 to -75°C. To this 1 - 10 moles, more preferably 4-5 moles of boron trifluoride is slowly passed at this temperature for 45 to 55 hours showing complete conversion of compound I to compound II (Scheme - 1).
The reaction mass is dumped into ice-water. This is stirred for 20 to 50 hours, preferably 25 to 35 hours at -50 °C to 70° C, preferably at 25 to 35°C to compounds having formula - III (Scheme -1). The solid thus obtained is tetrafluoroboric acid salt of compound of formula - III which is treated with base such as hydroxide or carbonates salts of lithium, sodium, potassium or ammonia. Potassium carbonate is the most preferred base, thereby liberating compound of formula (III), which is extracted in non-polar solvent, which is selected from aromatic hydrocarbon such as benzene, toluene, xylene and alkyl halides such as methylene chloride, chloroform, ethylene dichloride, trichloroethane. Toluene is the most preferred solvent for extraction. The solvent is removed by distillation at reduced pressure and the residue thus obtained is stirred with aliphatic hydrocarbon solvent, the solid is centrifuged and dried to get the pure compound having the formula III.
The invention is illustrated by the following representative example Example-I 8-ChIoro-5, 6-dihydro~[5,6]cycIohepta[l,2-b]-pyridin-ll-one (V): A solution of 30 kgs of (3-[2-(3-chlorophenyl)ethyl]-2-cyanopyridine) in 60 kg of anhydrous hydrofluoric acid is slowly passed through 40 kg of boron trifluoride at -60 °C to -75 °C in about 45 to 55 hours. The reaction mass is then dumped over ice-water and stirred for 25 to 35 hours at 25 °C to 35°C.
The solids are then filtered, washed with water, and then suspended in 500 L water; a solution of 12 kg of potassium carbonate in 120 L water is added to bring pH of aqueous solution more than 7.0, title compound (V) is extracted in toluene (460 L), toluene layer containing compound (V) is subjected to distillation to remove toluene to give a residue which is stirred with 144 L of hexane and the solution is cooled to 5° C to 10 °C. The product obtained by centrifugation is dried at 60°C -70°C to give 23 kg the title compound (V) with a yield of 76.4%.

Claims

We claim:
1) A process for the preparation of benzolycloheptapyridin-11-ones of the general formula III
Figure imgf000008_0001
wherein R1, R2, R3, R4, R5, R6 and R7 are independently selected from one or more of the following groups: hydrogen, halogen, C1-C6 alkyl, Cl - C6 alkoxy, which comprises a) reacting a compound of general formula (I),
Figure imgf000008_0002
wherein R1, R2, R3, R4, R5, R6 and R7 are as defined above, with anhydrous HF/BF3 at a temperature in the range of-100°C to -20°C, to produce a compound of formula (II),
Figure imgf000008_0003
(II)
wherein R ,ι , R , R . , R , R , R and R' are as defined above; and b) hydrolysing said compound of formula II to obtain said compound of the general formula III.
2. A process as claimed in claim 1 wherein said compound of formula I is reacted with said anhydrous HF/BF3 at a temperature in the range of -60 to -75°C.
3. A process as claimed in claim 1 or 2, wherein said hydrolysis is carried out by dumping the reaction product of said compound of formula II and said anhydrous HF/BF3 in ice-water, stirring the reaction mass for 20 - 80 hours at -50 °C to 70 °C to hydrolyse the compound of formula III.
4. A process as claimed in any preceding claim wherein said compound of formula III is isolated by collecting the salt of said compound of formula III with tetrafluoroboric acid, stirring the salt with water and adjusting the pH in the range of 6 to
10 with alkali to hberate said compound of formula III, extracting said compound of
Formula III with solvent extraction and distillation and recovering said compound of formula III in pure form by centrifugation and drying.
5. A process as claimed in any preceding claim wherein alkyl comprises straight or branched chain having 1 to 6 carbon atoms.
6. A process as claimed in any preceding claim wherein said halo is selected from fluorine, chlorine or bromine radicals
7. A process as claimed in any preceding claim wherein said anhydrous HF is employed in an amount of 10 to 60 moles with respect to the compound I used.
8. A process as claimed in claim 7 wherein anhydrous HF is used in a molar ratio of 20 to 30 mole with respect to the compound of formula I.
9. A process as claimed in any preceding claim wherein BF3 is used in a molar ratio of 1 to 10 moles to that of compound I.
10. A process as claimed in claim 9 wherein said molar ratio is preferably 4 to 5 moles.
11. A process as claimed in any preceding claim wherein said BF3 gas is passed in for a period ranging from 20 to 60 hours.
12. A process as claimed in claim 11 wherein BF3 gas is preferably passed in for a period ranging from 45 to 55 hours.
13. A process as claimed in claim 3 wherein said temperature is maintained within the range of25 °C to 35 °C.
14. A process as claimed in claim 3 wherein the reaction mass is stirred preferably for period ranging from 25 to 35 hours.
5 15. A process as claimed in any one of claims 3 to 14 wherein during hydrolysis the temperature is maintained in the range of 20 to 40°C.
16. A process as claimed in claim 4 wherein the pH adjusted is preferably in the range of 7 to 8.
17. A process as claimed in any one of claims claim 4 to 16, wherein said alkali is L0 selected from hydroxide or carbonate salt of lithium, sodium, potassium or ammonia.
18. A process as cliamed in claim 4 wherein the solid is extracted with organic solvent.
19. A process as claimed in claim 18 wherein the solvent is selected from aromatic hydrocarbons such as benzene, toluene, xylene, alkylhalides such as methylene chloride,
15 chloroform, ethylene dichloride, trichloroethane.
20. A process as claimed in any one of claims claim 4 to 19 wherein after distillation the residue is crystallized by stirring with hexane, heptane or cyclohexane. q \ [j£2"3 A process as claimed in any one of claims 4 to 20 wherein the product collected by centrifugation is dried at a temperature in the range of 60 - 70 °C.
>0
.5
30
PCT/IN2002/000246 2002-12-26 2002-12-26 A process for preparing benzocyclohetapyridin-11-ones WO2004058719A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2002368506A AU2002368506A1 (en) 2002-12-26 2002-12-26 A process for preparing benzocyclohetapyridin-11-ones
PCT/IN2002/000246 WO2004058719A1 (en) 2002-12-26 2002-12-26 A process for preparing benzocyclohetapyridin-11-ones

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IN2002/000246 WO2004058719A1 (en) 2002-12-26 2002-12-26 A process for preparing benzocyclohetapyridin-11-ones

Publications (1)

Publication Number Publication Date
WO2004058719A1 true WO2004058719A1 (en) 2004-07-15

Family

ID=32676750

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2002/000246 WO2004058719A1 (en) 2002-12-26 2002-12-26 A process for preparing benzocyclohetapyridin-11-ones

Country Status (2)

Country Link
AU (1) AU2002368506A1 (en)
WO (1) WO2004058719A1 (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000030589A2 (en) * 1998-11-20 2000-06-02 Schering Corporation Synthesis of intermediates useful in preparing tricyclic compounds
US20010016585A1 (en) * 1997-06-17 2001-08-23 Adriano Afonso Novel phenyl-substituted tricyclic inhibitors of farnesyl-protein transferase

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20010016585A1 (en) * 1997-06-17 2001-08-23 Adriano Afonso Novel phenyl-substituted tricyclic inhibitors of farnesyl-protein transferase
WO2000030589A2 (en) * 1998-11-20 2000-06-02 Schering Corporation Synthesis of intermediates useful in preparing tricyclic compounds

Also Published As

Publication number Publication date
AU2002368506A1 (en) 2004-07-22

Similar Documents

Publication Publication Date Title
EP2718262B1 (en) Apixaban preparation process
KR100632748B1 (en) Process for preparing thieno[3,2-c]pyridine derivatives
KR20060040758A (en) Process for preparing thieno[3,2-c]pyridine derivatives
MXPA05000997A (en) Preparation of 1h-imidazo [4,5-c] quinolin-4-amines via novel 1h-imidazo [4,5-c] quinolin-4-cyano and 1h-imidazo [4,5-c] quinolin-4-carboxamide intermediates.
CN110498770B (en) Method for preparing intermediate of oxaagolide
KR20010005907A (en) Crystalline amine salt of cefdinir
BRPI0609399A2 (en) method for producing 1-substituted 1h-imidazo [4,5-c] quinolin-4-amine compounds and intermediates thereof
KR20170023942A (en) Process for the preparation of 4-alkoxy-3-hydroxypicolinic acids
CZ20013658A3 (en) Synthesis and crystallization of compounds containing piperazine ring
WO1999051607A2 (en) Process for purification of a cephalosporin derivative
WO2004058719A1 (en) A process for preparing benzocyclohetapyridin-11-ones
EP1501838B1 (en) A process for the preparation of clopidogrel
Xu et al. Reactions of 2, 3‐dihydro‐1H‐1, 5‐benzodiazepines and chloroacetyl chlorides: Synthesis of 2a, 3, 4, 5‐tetrahydro‐azeto [1, 2‐a][1, 5] benzodiazepin‐1 (2H)‐ones
JPH0524158B2 (en)
EP2582690A1 (en) Process for preparation of 2, 3-diaryl-5-substituted pyridines and their intermediates
EP1098882B1 (en) A process for preparing benzocycloheptapyridin-11-ones
JP3448635B2 (en) Sulfenamide compound and method for producing the same
NO170010B (en) PROCEDURE FOR THE MANUFACTURING OF CERTAIN NIGHT-MAINTENANCE DERIVATIVES
JP4401167B2 (en) Synthesis process of tricyclic ketone intermediates
US5162534A (en) Process for the preparation of thiazoline derivatives
ZA200104631B (en) Process for preparing tricyclic compounds having antihistaminic activity.
DK141502B (en) Process for preparing a 7-acylamido-3-methyl-3-cephem-4-carboxylic acid ester.
JPWO2004103979A1 (en) Process for producing N- (2-amino-4,6-dichloropyrimidin-5-yl) formamide
EP0842179A1 (en) Production of optically active benzothiepin salts
PL165452B1 (en) Method of obtaining novel quinollinic salt

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LU MC NL PT SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP