WO2002070477A1 - Acide 2-methylindole-4-acetique, son procede de production et procede pour produire un produit intermediaire de celui-ci - Google Patents
Acide 2-methylindole-4-acetique, son procede de production et procede pour produire un produit intermediaire de celui-ci Download PDFInfo
- Publication number
- WO2002070477A1 WO2002070477A1 PCT/JP2002/001793 JP0201793W WO02070477A1 WO 2002070477 A1 WO2002070477 A1 WO 2002070477A1 JP 0201793 W JP0201793 W JP 0201793W WO 02070477 A1 WO02070477 A1 WO 02070477A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- formula
- reaction
- compound
- compound represented
- producing
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
Definitions
- the present invention relates to 2-methylindole-1-acetic acid, a method for producing the same, and a method for producing a synthetic intermediate thereof.
- the present invention relates to 2-methylindole-4-monoacetic acid represented by the following formula, a method for producing the same, and a method for producing an intermediate thereof.
- 2-Methylindole-4-monoacetic acid represented by the formula (I) is a synthetic intermediate of an indole derivative, which is an important compound as a pharmaceutical, and is a novel compound.
- Ts represents a tosyl group.
- the method for producing 2-methyl-4-oxo-1,4,5,6,7-tetrahydroindole which is a synthetic intermediate of the compound represented by the formula (I) of the present invention, comprises:
- JP-A-2-15058 describes that Are described.
- R represents H or CH 3
- R ′ represents H, CH 3 , or one CH 2 —C 6 H 5 ).
- the present inventors diligently studied a method for producing the 2-methylindole-14-acetic acid of the present invention in a high yield using inexpensive reagents under mild conditions suitable for industrial production. As a result, it has been found that the object is achieved by a novel production method represented by the following reaction process formula 1, and the present invention has been completed.
- 2-Methylindole-mono-acetic acid of the formula (I) is a novel compound. Reaction process formula 1
- R 1 represents C 1-4 alkyl
- T s represents a tosyl group.
- the starting compounds represented by the formulas (II-a), (II-b) and (IV) can be produced, for example, by the methods shown in the following reaction schemes 2 and 3. it can. Reaction process formula 2
- X represents a halogen atom
- R 1 represents C 1-4 alkyl
- R 2 represents trifluoromethyl, phenyl, or methyl at the p-position, and Or phenyl substituted with nitro.
- the compound represented by the formula (X), which is the starting compound of the reaction scheme 2, is For example, it can be produced by the method represented by the following reaction scheme 4.
- X represents a halogen atom.
- halogen atom means chlorine, bromine, iodine, and fluorine.
- C 1-4 alkyl represents methyl, ethyl, propyl, butyl and isomers thereof.
- the reaction in step [a] is a hydrolysis reaction under alkaline conditions.
- a water-miscible organic solvent ethanol, methanol, isopropanol, ethylene glycol dimethyl ether, tetrahydrofuran (THF ) Etc. or a mixture of them and water
- alkali potassium hydroxide, Using sodium hydroxide or the like at the reflux temperature of the solvent.
- the reaction in step [b] is a hydrolysis and decarboxylation reaction, for example, using a solvent (acetic acid, water or a mixture thereof), and an acid (acetic acid, sulfuric acid, hydrochloric acid, etc.) at 25 ° C. C. is carried out at 150.degree.
- a solvent acetic acid, water or a mixture thereof
- an acid acetic acid, sulfuric acid, hydrochloric acid, etc.
- the reaction in step [c] is a hydrolysis reaction under alkaline conditions, for example, an organic solvent miscible with water (ethanol, methanol, isopropanol, ethylene glycol dimethyl ether, tetrahydrofuran (THF), or the like) This is carried out at a reflux temperature of the solvent using an aqueous solution of an alkali (eg, potassium hydroxide, sodium hydroxide, etc.).
- an organic solvent miscible with water ethanol, methanol, isopropanol, ethylene glycol dimethyl ether, tetrahydrofuran (THF), or the like
- an alkali eg, potassium hydroxide, sodium hydroxide, etc.
- the reaction in step [d] is a tosylation reaction.
- a quaternary ammonium salt tetrabutylammonium
- organic solvent acetonitrile, THF, ethylene glycol dimethyl ether, diglyme, etc.
- the reaction is carried out at 0 to 50 ° C using tosyl halide (tosyl fluoride, tosyl fluoride, etc.) in the presence of an aqueous solution of an alkali (sodium hydroxide, potassium hydroxide, etc.).
- the reaction in step [e-1] is a carbon-enrichment reaction.
- [e-1-a] Dean-Stark, acetic acid in an organic solvent (toluene, xylene, etc.)
- the reaction is carried out using a cyanoacetate (methyl cyanate, ethyl cyanate, etc.) at the reflux temperature of the solvent in the presence of ammonium and an organic acid (acetic acid, propionic acid, etc.).
- 2-cyano 2- represented by the formula (VI I) can be obtained in a high yield by using a very inexpensive cyanate ester.
- [2- Methyl-11-tosyl-5,6,7-trihydride-indo-l-41-ylidene] acetic acid ester can be produced.
- the reaction in step [e-2] is a carbon increase reaction.
- an organic solvent toluene, xylene, etc.
- ammonium acetate and organic acids acetic acid, propionic acid, etc.
- 2- [2-methyl-1-] represented by the formula (VIII) can be obtained in high yield using inexpensive malononitrile.
- the reaction in step [f] is a halogenation reaction, for example, in an organic solvent (THF, dimethylformamide (DMF), etc.), a base (sodium hydride, lithium diisopropyl Amide, sodium t-butoxy, potassium t-butoxide, etc.) at 20-55 ° C, preferably cooled sulfonyl chlorides (benzenesulfonyl chloride, p-toluenesulfonyl chloride, p-chloro) Benzenesulfonyl chloride, p-nitrobenzene benzenesulfonyl chloride, trifluoromethanesulfonyl chloride, etc.) at 178 to 30 ° C.
- an organic solvent THF, dimethylformamide (DMF), etc.
- a base sodium hydride, lithium diisopropyl Amide, sodium t-butoxy, potassium t-butoxide, etc.
- the compounds represented by the formulas (V) and (VI), which are chlorinated to the ⁇ -position having the following structural formula, are obtained.
- the reaction in step [g] is an aromatization reaction.
- an organic solvent DMF, dimethylimidazolidinone, dimethylacetamide, dimethylsulfoxide, etc.
- lithium halide The reaction is carried out at 80 to 120 ° C using lithium bromide, lithium chloride or the like.
- reaction in step [h] is a reaction for the synthesis of enamine, for example, in an organic solvent (acetonitrile, THF, ethylene glycol dimethyl ether, diglyme, isopropanol, etc.), 2-aminopropionaldehyde Performed at the reflux temperature of the solvent using dimethyl acetal
- the reaction in the step [i] is a cyclization reaction.
- the compound prepared in the step [h] is added to an aqueous solution of an acid (p-toluenesulfonic acid, hydrochloric acid, etc.), which is preferably maintained at a temperature of 65 ° C. or higher.
- an organic solvent acetonitrile, THF, ethylene glycol dimethyl ether, diglyme, isopropanol, etc.
- the reaction in step U] is (1) a reaction for introducing an acetylstyl group, followed by (2) a cyclization reaction.
- the reaction for introducing an acetylmethyl group is performed, for example, using a base (potassium hydroxide, sodium hydroxide or Triton B) in a water-miscible organic solvent (methanol, ethanol, isopropanol, acetonitrile, etc.).
- a base potassium hydroxide, sodium hydroxide or Triton B
- a water-miscible organic solvent methanol, ethanol, isopropanol, acetonitrile, etc.
- the cyclization reaction is carried out, for example, in a water-miscible organic solvent (methanol, ethanol, isopropanol, acetonitrile, etc.) using ammonium acetate at room temperature to the reflux temperature of the solvent for 1 hour to 5 hours.
- a water-miscible organic solvent methanol, ethanol, isopropanol, acetonitrile, etc.
- the compound represented by the formula (X) can be produced from the starting material represented by the formula (XIV) in one pot from the starting material, without the necessity of isolating the compound during the reaction step. .
- Each step is preferably performed in an inert gas (eg, argon) atmosphere.
- an inert gas eg, argon
- the compound used as a starting material is a known compound, or can be easily produced from a known compound by a known method.
- Each reagent in the present invention is known per se or can be produced by a known method.
- the reaction product is purified by conventional purification means, for example, distillation under normal or reduced pressure, high performance liquid chromatography using silica gel or magnesium gayate, thin-layer chromatography, or column chromatography. It can be purified by a method such as chromatography, washing, or recrystallization. Purification may be performed for each reaction or may be performed after completion of several reactions.
- conventional purification means for example, distillation under normal or reduced pressure, high performance liquid chromatography using silica gel or magnesium gayate, thin-layer chromatography, or column chromatography. It can be purified by a method such as chromatography, washing, or recrystallization. Purification may be performed for each reaction or may be performed after completion of several reactions.
- the method described in (1) is completely different from the present invention in starting materials and reaction steps, and the method described in (2) uses an expensive reagent in the first step and performs the reaction at a high temperature in the second step. It is not an industrially suitable method. Therefore, the production methods disclosed in these documents do not suggest the production method of the present invention which uses inexpensive reagents and is carried out under mild conditions suitable for industrial production.
- the process for producing 4-oxo-2-methyl-4,5,6,7-tetrahydroindole represented by the formula (X) in the present invention comprises, as described above, (3) US Pat. No. 4,868,315, and (4) Jus tus Liebigs Ann. Chem., 655, 20-26 (1952), and (5) JP-A-2-15058.
- the method described in (3) requires the complicated operation of back extraction in the first step, the necessity of isolating the compound during the reaction step, and the reaction in the first and second steps. This takes two or three days, and this manufacturing method is not industrially suitable.
- the reaction can be carried out promptly from room temperature to the reflux temperature of the solvent used in the reaction, and the target compound can be obtained without complicated operation even after the completion of the reaction.
- the method described in (4) is different from the present invention in the starting materials, and in the reaction step, ammonia is used, and the reaction at a high temperature is required. Therefore, the method described in a closed apparatus such as a autoclave is used. It requires a heating process and is not suitable for industrial production.
- the reaction can be carried out from room temperature to the reflux temperature of the solvent using ammonium acetate, and thus no special device is required.
- the method described in (5) is different from the present invention in the starting material. In the present invention, there is no need to isolate the starting material compound described in (5) in the course of the reaction step.
- the compound in which the desired a-position is chlorinated is more selective than the compound in which the by-product position is chlorinated. It can be produced with high yield and high yield, and is superior to the production method described in (7).
- Example 1 (1)
- IR Liquid film: 3255, 3064, 2941, 2834, 1738, 1669, 1552, 1455, 1432, 1369, 1319, 1257, 1191, 1134, 1067, 981, 968, 950, 937, 908, 859, 809, 764, 672, 651, 610, 557, 535, 511, 468 cm one 1.
- Example 3 (1)
- Example 2 The compound prepared in Example 2 at an internal temperature of 73 ° C was added dropwise to a 2M p-toluenesulfonic acid aqueous solution (33.5mL) at an internal temperature of 80 ° C while maintaining the internal temperature of the solution at 73 ° C or higher. .
- the mixture was heated and stirred at an internal temperature of 78 ° C for 2 hours.
- the pH was adjusted to 11 with a 4 M aqueous sodium hydroxide solution.
- the mixture was stirred at room temperature for 1 hour, and the precipitated crystals were collected by filtration. The crystals are washed with water and dried under reduced pressure at 40 ° C for 15 hours.
- the title compound (3.73 g, yield 56%) was obtained.
- Example 3 (2) The compound (lllg) produced in Example 3 (2) was suspended in acetonitrile (1110 ml). Tetrabutylammonium bromide (72 g) and 50% aqueous sodium hydroxide solution (596 ml) were added to the suspension at room temperature. A solution of tosyl chloride (284 g) in THF (555 ml) was added dropwise to the suspension at room temperature, and the mixture was stirred at room temperature for 1 hour. Add the reaction solution to water (6700ml) and at 15 ° C
- Example 4 The compound prepared in Example 4 (199 g) was dissolved in toluene (1990 ml) at 14 ° C, ammonium acetate (55.6 g) and acetic acid (157.5 g) were added at 16 ° C, and further, ethyl ethyl acetate (111.8 g) was added. g) was added and the mixture was heated under reflux. The reaction was carried out for 19 hours using Dean Stark while distilling off water. The reaction solution was concentrated and azeotroped with toluene. Isopropanol (1990 ml) and water (995 ml) were added to the residue, and the mixture was stirred and dissolved by heating.
- IR (KB r): 3754, 3678, 3449, 2934, 2216, 1714, 1655, 1596, 1536, 1413, 1373, 1349, 1333, 1243, 1221, 1193, 1166, 1091, 1059, 949, 810, 774, 704, 686, 652, 591, 544, 429 cm “ 1 ;
- the title compound having the following physical data was obtained by performing the same operation as in Example 5 using the compound produced in Example 4 and malononitrile instead of ethyl cyanoacetate.
- IR (KB r): 3754, 3678, 3449, 2934, 2216, 1714, 1655, 1596, 1536, 1413, 1373, 1349, 1333, 1243, 1221, 1193, 1166, 1091, 1059, 949, 810, 774, 704, 686, 652, 591, 544, 429 cm— 1 ;
- Example 7 The same operation as in Example 7 was carried out using the compound produced in Example 5 (1) to give the title compound having the following physical data.
- I R liquid film: 3057, 2983, 2930, 1747, 1598, 1572, 1494, 1432, 1390, 1370, 1307, 1293, 1256, 1221, 1189, 1178, 1159, 1122, 1099, 1068, 1029,
- the solution was stirred for 30 minutes, and the precipitated crystals were collected by filtration and washed twice with water (220 ml).
- the crystals were added to isopropanol Z water (122 ml / 3 68 ml), dissolved by heating, and allowed to cool to room temperature. After aging the solution at 4 ° C for 1 hour, the crystals were collected by filtration, washed twice with isopropanol / water (1/3; 80 ml), and dried at 40 for 19 hours.
- the compound (30.6 g, yield 74.8%) was obtained.
- IR (KB r): 3855, 3823, 3678, 3652, 3631, 3405, 2906, 1702, 1617, 1557, 1509, 1439, 1405, 1348, 1295, 1278, 1253, 1214, 1178, 1056, 955, 760, 708, 633, 513, 483, 420 cm " 1 ;
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP02705046A EP1367050A4 (en) | 2001-03-01 | 2002-02-27 | 2-METHYLINDOLE-4-ACETIC ACID, PROCESS FOR PRODUCING THE SAME, AND PROCESS FOR PRODUCING INTERMEDIATE PRODUCT THEREOF |
US10/469,385 US20040092750A1 (en) | 2001-03-01 | 2002-02-27 | 2-methylindole-4-acetic acid, process for producing the same, and process for producing intermediate therefor |
HU0400606A HUP0400606A2 (hu) | 2001-03-01 | 2002-02-27 | 2-Metil-indol-4-ecetsav és intermedierei és eljárás előállításukra |
JP2002569797A JPWO2002070477A1 (ja) | 2001-03-01 | 2002-02-27 | 2−メチルインドール−4−酢酸、その製造方法およびその合成中間体の製造方法 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2001057165 | 2001-03-01 | ||
JP2001-57165 | 2001-03-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2002070477A1 true WO2002070477A1 (fr) | 2002-09-12 |
Family
ID=18917086
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2002/001793 WO2002070477A1 (fr) | 2001-03-01 | 2002-02-27 | Acide 2-methylindole-4-acetique, son procede de production et procede pour produire un produit intermediaire de celui-ci |
Country Status (5)
Country | Link |
---|---|
US (1) | US20040092750A1 (ja) |
EP (1) | EP1367050A4 (ja) |
JP (1) | JPWO2002070477A1 (ja) |
HU (1) | HUP0400606A2 (ja) |
WO (1) | WO2002070477A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2465673T3 (es) | 2007-04-16 | 2014-06-06 | Hutchison Medipharma Enterprises Limited | Derivados de pirimidina |
US7829574B2 (en) | 2008-05-09 | 2010-11-09 | Hutchison Medipharma Enterprises Limited | Substituted quinazoline compounds and their use in treating angiogenesis-related diseases |
US8426430B2 (en) * | 2008-06-30 | 2013-04-23 | Hutchison Medipharma Enterprises Limited | Quinazoline derivatives |
TW201008933A (en) * | 2008-08-29 | 2010-03-01 | Hutchison Medipharma Entpr Ltd | Pyrimidine compounds |
MX2019000753A (es) * | 2016-07-22 | 2019-06-03 | Syngenta Participations Ag | Proceso para preparacion de dinitrilos del acido fenilmalonico. |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1150397A (en) * | 1967-02-23 | 1969-04-30 | Parke Davis & Co | New Indole-4-Acetic Acid Compounds and Methods for Their Production |
US4745222A (en) * | 1983-05-25 | 1988-05-17 | Merrell Dow Pharmaceuticals Inc. | Novel aryloxycycloalkanolaminoalkylene aryl ketones |
JPH0215058A (ja) * | 1988-07-01 | 1990-01-18 | Nippon Zeon Co Ltd | 2−置換−4−オキソテトラヒドロインドール類の製造方法 |
EP0887342A2 (en) * | 1997-06-26 | 1998-12-30 | Eli Lilly And Company | Process for preparing 4-substituted-1H-indole-3-glyoxamides |
WO2001066520A1 (fr) * | 2000-03-09 | 2001-09-13 | Ono Pharmaceutical Co., Ltd. | Derives indole, procede de preparation de ces derives et leur utilisation |
-
2002
- 2002-02-27 WO PCT/JP2002/001793 patent/WO2002070477A1/ja not_active Application Discontinuation
- 2002-02-27 JP JP2002569797A patent/JPWO2002070477A1/ja not_active Withdrawn
- 2002-02-27 HU HU0400606A patent/HUP0400606A2/hu unknown
- 2002-02-27 US US10/469,385 patent/US20040092750A1/en not_active Abandoned
- 2002-02-27 EP EP02705046A patent/EP1367050A4/en not_active Withdrawn
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1150397A (en) * | 1967-02-23 | 1969-04-30 | Parke Davis & Co | New Indole-4-Acetic Acid Compounds and Methods for Their Production |
US4745222A (en) * | 1983-05-25 | 1988-05-17 | Merrell Dow Pharmaceuticals Inc. | Novel aryloxycycloalkanolaminoalkylene aryl ketones |
JPH0215058A (ja) * | 1988-07-01 | 1990-01-18 | Nippon Zeon Co Ltd | 2−置換−4−オキソテトラヒドロインドール類の製造方法 |
EP0887342A2 (en) * | 1997-06-26 | 1998-12-30 | Eli Lilly And Company | Process for preparing 4-substituted-1H-indole-3-glyoxamides |
WO2001066520A1 (fr) * | 2000-03-09 | 2001-09-13 | Ono Pharmaceutical Co., Ltd. | Derives indole, procede de preparation de ces derives et leur utilisation |
Non-Patent Citations (1)
Title |
---|
See also references of EP1367050A4 * |
Also Published As
Publication number | Publication date |
---|---|
EP1367050A4 (en) | 2005-09-21 |
HUP0400606A2 (hu) | 2004-12-28 |
EP1367050A1 (en) | 2003-12-03 |
US20040092750A1 (en) | 2004-05-13 |
JPWO2002070477A1 (ja) | 2004-07-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JPS63139182A (ja) | チアゾリジンジオン誘導体の製造法 | |
JP3850838B2 (ja) | トランス−4−アミノ−1−シクロヘキサンカルボン酸誘導体の製造方法 | |
JPH0489464A (ja) | メトキシイミノアセトアミド化合物の製造法 | |
WO2002070477A1 (fr) | Acide 2-methylindole-4-acetique, son procede de production et procede pour produire un produit intermediaire de celui-ci | |
JPH0610174B2 (ja) | アミノフエノ−ル誘導体 | |
JP6256484B2 (ja) | ピリダジン化合物の製造方法 | |
JP2001247570A (ja) | インドール酢酸化合物及びその製造方法 | |
WO1999016759A1 (fr) | Procede de production d'alkylamines substituees ou de leurs sels | |
JP4173599B2 (ja) | 6−ヒドロキシ−2−オキソ−1,2,3,4−テトラヒドロキノリンの製造方法 | |
HU200459B (en) | New process for producing 7-bromo-beta-carboline compounds | |
EP0489547B1 (en) | A process for the preparation of a 3-alkylated indole, intermediates, and a process for the preparation of a derivative thereof | |
JP3880883B2 (ja) | ピリジン誘導体、その製造方法、及び除草剤中間体としての用途 | |
US5578728A (en) | Process for the preparation of a benzo(a)quinolizione derivative | |
KR100424341B1 (ko) | 1-메틸인다졸-3-카르복실산의 제조방법 | |
JP4061333B2 (ja) | 2−(ピラゾール−1−イル)ピリジン誘導体 | |
JPH0525162A (ja) | キノロン誘導体およびその製造法 | |
JPH0948778A (ja) | 2−置換−3−アルコキシ−5−(ピロール−2−イル)フラン誘導体 | |
JP2711435B2 (ja) | 新規な2,3−ジヒドロ−4h−1−ベンゾピラン−4−オン誘導体またはその塩 | |
JPH09143127A (ja) | ニトロトルエン誘導体およびその製造方法 | |
KR100228327B1 (ko) | 3-알킬화 인돌의 제조방법 | |
JP2024511422A (ja) | 5-{5-クロロ-2-[(3s)-3-[(モルホリン-4-イル)メチル]-3,4-ジヒドロイソキノリン-2(1h)-カルボニル]フェニル}-1,2-ジメチル-1h-ピロール-3-カルボン酸誘導体を合成するための新規な製造方法及び医薬化合物を製造するためのその適用 | |
JP2002265449A (ja) | 2−アミノ−3−ベンゾイルピリジン誘導体の製造法 | |
JPH0551365A (ja) | 4−オキソキノリン−3−カルボン酸類の製造方法 | |
Labanauskas et al. | Synthesis of 1-substituted 4-[4-(1H-indol-3-yl) butyl] piperazines | |
JP2004244362A (ja) | 1,2−ジ置換−1,4−ジヒドロ−オキソキノリン誘導体の製造方法 |
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 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 SI 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 CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE 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) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2002569797 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2002705046 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 10469385 Country of ref document: US Ref document number: 028057511 Country of ref document: CN |
|
WWP | Wipo information: published in national office |
Ref document number: 2002705046 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 2002705046 Country of ref document: EP |