WO2005009991A1 - 1,2,4−トリアゾール化合物の製造方法及びその中間体 - Google Patents
1,2,4−トリアゾール化合物の製造方法及びその中間体 Download PDFInfo
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- WO2005009991A1 WO2005009991A1 PCT/JP2004/010456 JP2004010456W WO2005009991A1 WO 2005009991 A1 WO2005009991 A1 WO 2005009991A1 JP 2004010456 W JP2004010456 W JP 2004010456W WO 2005009991 A1 WO2005009991 A1 WO 2005009991A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
Definitions
- the present invention relates to a method for producing a novel 1,2,4-triazole compound having an aromatic substituent at the 3- and 5-positions and an intermediate thereof.
- Patent Document 1 A novel 1,2,4-triazole compound having an aromatic group at the 5-position that inhibits xanthine oxidase and is useful for the treatment of gout and hyperuricemia.
- Patent Document 1 A novel 1,2,4-triazole compound having an aromatic group at the 5-position that inhibits xanthine oxidase and is useful for the treatment of gout and hyperuricemia.
- TMS represents a trimethylsilyl group
- Ar represents an aromatic group
- Patent Document 1 JP 2002-017825 A
- an aromatic pyridine optionally having a pyridine nonoxydoxyl group at the 3-position which may have a substituent other than the 2-position in advance.
- a 1,2,4 triazole derivative having a group at the 5-position was prepared, and the hydrogen atom bonded to the nitrogen atom of the triazole ring of this compound was converted to a group that became soluble in an organic solvent and could be removed by an acid. later It may have a substituent by removing the group in the next step, and the 2-cyanoviridine 4-yl group may be in the 3-position and may have a substituent.
- 1,2,4-Triazole compound having an aromatic group at the 5-position It was found that the compound can be obtained in extremely high yield without the need for isolation in each step), thus completing the present invention.
- Rd represents a pyridine N-oxide-4-yl group which may have a substituent other than at the 2-position
- Rb represents a pyridinole group or a phenyl group which may have a substituent.
- Rc represents a group which renders the compounds of formulas (3) and (4) soluble in an organic solvent and can be removed by an acid; and in the compounds of formulas (3) and (4), any one of the triazole rings Ra represents a 2-cyanopyridine-4-yl group which may have a substituent, Ra represents a halogen atom or a sulfonic acid residue, and represents a group represented by the formula ( In the compounds (1) and (5), a hydrogen atom is bonded to any nitrogen atom of the triazole ring.
- the present invention provides a compound represented by the general formula (3) characterized by reacting a compound represented by the formula (2) with a compound represented by the general formula (1). It provides a method for producing a salt or a hydrate thereof.
- the present invention provides a method for producing a compound represented by the general formula (4), a salt thereof or a hydrate thereof, which comprises reacting a compound represented by the general formula (3) with a nitrile diluent. It is provided. Further, the present invention is characterized in that a compound represented by the general formula (3) is reacted with a nitrilating agent to obtain a compound represented by the general formula (4), and then the acid is reacted with the compound in the next step.
- the compounds represented by the general formulas (3) and (4) are useful as production intermediates.
- A is Rd or Ra, that is, a pyridine N-oxyditol 41-yl group optionally having a substituent other than the 2-position or an optionally substituted 2_cyanopyridine 1-41 And Rb and Rc are the same as defined above), a 1,2,4-triazole aldehyde compound, a salt thereof or a hydrate thereof.
- the group which can be substituted with the pyridine N-oxido 41-yl group represented by Rd and the 2--cyanoviridine 14-yl group represented by Ra include a nitro group, a halogen atom, and a lower alkyl group.
- Examples of the group that can be substituted for the pyridyl group or phenyl group represented by Rb include a cyano group and a nitro group.
- examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
- examples of the lower alkyl group include a linear or branched alkyl group having 16 carbon atoms, such as a methyl group, an ethyl group, an isopropyl group, and an isobutyl group.
- examples of the substituted or unsubstituted lower alkoxy group include straight-chain or branched-chain substituted or unsubstituted alkoxy groups having 16 carbon atoms, such as methoxy group, ethoxy group, isopropoxy group, isobutoxy group, and methoxy group.
- the lower alkylthio group include a linear or branched alkylthio group having 16 carbon atoms, such as a methylthio group, an ethylthio group, and an isopropylthio group.
- the lower alkyl group of the N-lower alkylpiperazino group and the lower alkylamino group include a straight-chain or branched-chain alkyl group having 116 carbon atoms.
- Rc is not limited as long as it makes the compounds represented by formulas (3) and (4) soluble in an organic solvent and can be removed with an acid.
- Ry represents a substituted or unsubstituted alkyl group
- a diphenylmethyl group a p_alkoxybenzyl group, and the like.
- the substituted or unsubstituted alkyl group represented by Ry includes a linear or branched alkyl group having 16 carbon atoms (abbreviated as C alkyl group), a phenyl C alkyl group, C
- examples of the C alkyl group and C alkoxy include the lower alkyl
- the same as the group and the substituted or unsubstituted lower alkoxy group for example, a methyl group, an ethyl group, an isopropyl group, a methoxy group, an ethoxy group, an isopropoxy group and the like can be mentioned.
- Examples of the p-alkoxybenzyl group include a p_C alkoxybenzyl group.
- Particularly preferred examples of the formula Rc include a benzyloxymethyl group, a methoxymethyl group, a methoxyethoxymethyl group, a trimethylsilylethoxymethyl group, a diphenylmethyl group, and a p-methoxybenzinole group.
- the compound represented by the general formula (1) as a raw material is described, for example, in JP-A-47-7120, JP-A-61-152661, JP-A-62-149673, and JP-A-2002-149673.
- R 1 represents a lower alkyl group
- Rb and Rd represent the same as described above.
- examples of the alkali metal alkoxide include sodium methoxide.
- the reaction of 4-cyanopyridine N-oxides (7) with alkali metal alkoxides (8) should be carried out in alcohol at room temperature at 180 ° C for several hours.
- the reaction with the hydrazide (9) may be carried out at 50 to 100 ° C for 30 minutes and several hours, and the subsequent heating and ring closing reaction may be carried out by heating at about 100 to 150 ° C.
- the reaction from 4-cyanopyridine N-oxides (7) to the compound of the formula (1) can be carried out in one pot without isolating any intermediate, and the yield is high (1). ) Can be obtained.
- the reaction between the starting compound (1) and the compound of the formula (2) is carried out in an organic solvent in the presence of a base.
- the organic solvent include N, N-dimethylacetamide, N, N-dimethylformamide, N-methylpyrrolidone, acetonitrile, dioxane and the like. Of these, polar solvents such as dimethylacetamide and dimethylformamide are preferred.
- organic amines such as trimethylamine, triethylamine, diisopropylamine and diisopropylethylamine are preferred.
- the reaction may be performed at 50-150 ° C for 16 hours.
- the nitrilation reaction of the compound (3) is carried out in an organic solvent by a combination of a nitrile arresting agent such as trimethylsilyl nitrile, potassium cyanide, sodium cyanide and the following reagents.
- a nitrile arresting agent such as trimethylsilyl nitrile, potassium cyanide, sodium cyanide and the following reagents.
- reaction solvent N, N-dimethylacetamide, N, N-dimethylformamide, N-methylpyrrolidone, tetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane and the like can be used.
- Dimethylacetamide is preferred.
- the reaction temperature and time are 0 to 10 ° C, preferably 5 ° C or lower, and the nitrilating agent is added. After stirring for 30 minutes to 12 hours, the reaction is performed at 20 to 70 ° C, preferably 30 to 60 ° C Stir for 5-20 hours, preferably 715 hours.
- any acid capable of removing the group and not destroying the compound of the present invention can be used.
- p-toluenesulfonic acid methanesulfonic acid, etc.
- Inorganic acids such as mechanical acid, hydrochloric acid, and sulfuric acid;
- reaction solvent examples include methanol, ethanol, isopropanol, and 2-butanol, or a mixed solvent of alcohols and toluene, and ethanol and isopropanol are preferred.
- the reaction temperature and time are 50 ° C to 150 ° C, preferably 80 ° C to 120 ° C, for 3 hours to 20 hours, preferably 5 hours to 15 hours.
- reaction from compound (1) to compound (5) can be carried out in an organic solvent, and can be carried out in one pot without isolating the intermediate. It is industrially advantageous.
- the obtained compound (5) can be isolated as an addition salt of the acid used for the acid treatment.
- the acid addition salt can be converted to the free base of compound (5) by neutralizing the acid addition salt if desired.
- the base used for the neutralization of the compound (5) differs depending on the acid to be neutralized, but preferably sodium hydrogen carbonate, potassium carbonate and the like can be used.
- Alcohol-based solvents can be used as the reaction solvent. Preferred alcohols include ethanol, isopropanol, and lower alcohols such as 2-butanol.
- the reaction is carried out at a temperature of 10 ° C to 50 ° C, preferably 20 ° C to 30 ° C.
- the 1,2,4-triazolyl conjugate having the basic skeleton according to the present invention has a force S in which the following isomers (A), (B), and (C) are present. All were represented as 1,2,4-triazole and represented as a general formula.
- Ra and Rb represent the same as described above, and Re represents a hydrogen atom or Rc.
- N, N-dimethylacetamide of the yellow crystals (70. Og) obtained in Reference Example 1 Benzylchloromethyl ether (46.6 mL) was added dropwise to the suspension (700 mL), and the mixture was stirred at room temperature for 10 minutes, and then triethylamine (46.9 mL) was added dropwise, and the mixture was heated at an internal temperature of 85 ° C for 2 hours.
- a solution of N-benzyloxymethyl-5_ (1-oxy-1-4-pyridyl) _3_ (4_pyridyl 2,4_triazole was obtained. A part of this solution was isolated and the following data was obtained.
- the product was white crystals (mixture of isomers).
- the solution obtained in (1) was cooled to an internal temperature of 5 ° C, and trimethylsilyl nitrile (46.8 mL) was added dropwise. After stirring for 10 minutes, N, N-dimethylcarbamic acid chloride (64.7 mL) was added dropwise. Then, the mixture was stirred at an internal temperature of 5 ° C for 1 hour. Next, the internal temperature was gradually raised to 35 ° C., and the mixture was stirred for 10 hours. The reaction solution was cooled to 5 ° C., and a 0.5 mol / L aqueous solution of potassium carbonate (878 mL) was gradually added to make the reaction solution basic.
- Example 2_propanol 700 mL
- P-toluenesulfonic acid monohydrate 151.16 g
- the white crystals were dried under reduced pressure at 60 ° C. for 15 hours to obtain 106.
- Og of the title compound as white crystals.
- 90.0 g of these crystals were suspended in a mixture of 2-butanol (49 mU and water (491 mL) and heated for 1 hour at an internal temperature of 80 ° C.
- the internal temperature was returned to room temperature, and the crystals were collected by filtration.
- the crystals obtained by washing with a mixed solution (270 mL ⁇ 3) of 2-butanol / aqueous solution (1:10) were dried under reduced pressure at 60 ° C. for 15 hours to obtain 75.7 g of the highly pure title compound.
- the reaction solution obtained in (1) was cooled to an internal temperature of 15 ° C, and trimethylsilyl nitrile (23.8 mL) was added dropwise. After stirring for 10 minutes, N, N-dimethylcarbamic acid chloride (26.7 mL) was added. The mixture was added dropwise and stirred at room temperature for 1 hour and at an internal temperature of 57 ° C for 3 hours. The reaction solution was cooled in an ice bath, and a 0.5 mol / L aqueous solution of potassium carbonate (581 mL) was gradually added to make the reaction solution basic.
- reaction solution of (1) was cooled in an ice bath for 25 minutes, trimethylsilyl nitrile (0.67 mL) was added dropwise, and the mixture was stirred for 10 minutes.N, N-dimethylcarbamic acid chloride (0.93 mL) was added dropwise, and the mixture was added to ice. Stirred in the bath for 1 hour. Thereafter, the external temperature was raised to 60 ° C and the mixture was stirred for 3 hours.
- the reaction solution was cooled in an ice bath, and a 0.5 mol / L aqueous potassium carbonate solution (12. OmL) was gradually added to make the reaction solution basic.
- the solution was extracted with toluene (30.
- reaction solution of (1) was cooled in an ice bath for 35 minutes, trimethylsilyl nitrile (0.67 mL) was added dropwise, and the mixture was stirred for 10 minutes, and N, N-dimethylcarbamic acid chloride (0.92 mL) was added dropwise. Stirred for hours. Thereafter, the external temperature was raised to 60 ° C., and the mixture was stirred for 3 hours.
- the reaction solution was cooled in an ice bath, and a 0.5 mol ZL aqueous potassium carbonate solution (12. OmL) was gradually added to make the reaction solution basic.
- benzhydryl chloride (0.85 mL) was added dropwise to a suspension of the yellow crystals (1.00 g) obtained in Reference Example 1 in N, N-dimethylacetamide (10. OmL), and the mixture was cooled to room temperature. Then, diisopropylethylamine (0.67 mL) was added dropwise, and the mixture was heated at an external temperature of 90 ° C for 5 hours and 20 minutes. After leaving the reaction solution at room temperature overnight, trimethylsilyl nitrile (0.67 mL) was added dropwise, and after stirring for 10 minutes, N, N-dimethylcarbamic acid chloride (0.92 mL) was added dropwise, and the external temperature was reduced to 60 ° C.
- benzyl chloromethyl ether (0.32 mL) was added dropwise to a suspension of the yellow crystals (0.50 g) obtained in Reference Example 2 in N, N-dimethylacetamide (5. OmL), and the mixture was added at room temperature for 10 minutes.
- triethylamine (0.32 mL) was added dropwise, and the mixture was heated at an external temperature of 90 ° C for 3 hours.
- N-benzyloxymethinole 5_ (1_oxy-1-4-pyridyl) _3_ (2-chloro-1-4-pyridyl) -11,2,4-triazole solution obtained in (1) was cooled in an ice bath. Then, trimethylsilyl ditrinole (0.58 mL) was added dropwise, and the mixture was stirred for 10 minutes, N, N-dimethylcarbamic acid chloride (0.80 mL) was added dropwise, and the mixture was stirred in an ice bath for 1 hour. Thereafter, the external temperature was raised to 60 ° C and the mixture was stirred for 3 hours.
- reaction solution was cooled in an ice bath, and a 0.5 mol / L aqueous potassium carbonate solution (14.5 mL) was gradually added to make the reaction solution basic.
- N-benzyloxymethinolate 5_ (1_oxy_4_pyridyl) _3_ (2-phenyl-2-pyridyl) _1,2,4-triazole solution obtained in (1) was cooled in an ice bath, and trimethylsilyl nitrate was added. Tolyl (0.46 mL) was added dropwise, and the mixture was stirred for 10 minutes. N, N-dimethylcarbamic acid chloride (0.63 mL) was added dropwise, and the mixture was stirred in an ice bath for 1 hour. Thereafter, the external temperature was raised to 60 ° C and the mixture was stirred for 3 hours.
- reaction solution was cooled in an ice bath, and a 0.5 mol ZL aqueous potassium carbonate solution (8.6 mL) was gradually added to make the reaction solution basic.
- N-benzyloxymethinole obtained in (1) 5_ (1_oxy-1_4_pyridyl) _3_ [3-cyano-4- ⁇ 2- (2-methoxyethoxy) ethoxy ⁇ phenyl] -1
- the 2,2,4-triazole solution was cooled in an ice bath, and trimethylsilyl nitrile (0.42 mL) was added dropwise.
- N, N-dimethylcarbamic acid chloride (0.58 mL) was added dropwise, and the mixture was cooled in an ice bath.
- the external temperature was raised to 60 ° C, and the mixture was stirred for 3 hours.
- reaction solution was cooled in an ice bath, and a 0.5 mol / L aqueous solution of lithium carbonate (7.9 mU) was gradually added to make the reaction solution basic.
- the solution was extracted five times with toluene, and magnesium sulfate was added. Then, the solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (methanol: chloroform: 1:40) to obtain 1.12 g of the title compound as yellow crystals. (Isomer mixture)
- Test example Serum uric acid lowering effect
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Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
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JP2005512023A JP3779725B2 (ja) | 2003-07-24 | 2004-07-23 | 1,2,4−トリアゾール化合物の製造方法及びその中間体 |
CA002531912A CA2531912A1 (en) | 2003-07-24 | 2004-07-23 | Process for producing 1,2,4-triazole compound and intermediate therefor |
AU2004259582A AU2004259582A1 (en) | 2003-07-24 | 2004-07-23 | Process for producing 1,2,4-triazole compound and intermediate therefor |
EP04747845A EP1650204A4 (en) | 2003-07-24 | 2004-07-23 | PROCESS FOR PREPARING A 1,2,4-TRIAZOL COMPOUND AND INTERMEDIATE PRODUCTS THEREFOR |
US10/565,678 US20060189811A1 (en) | 2004-07-23 | 2004-07-23 | Process for producing 1,2,4-triazole compound and intermediate therefor |
Applications Claiming Priority (2)
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JP2003201286 | 2003-07-24 | ||
JP2003-201286 | 2003-07-24 |
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EP (1) | EP1650204A4 (ja) |
JP (1) | JP3779725B2 (ja) |
KR (1) | KR20060037373A (ja) |
CN (1) | CN1826335A (ja) |
AU (1) | AU2004259582A1 (ja) |
CA (1) | CA2531912A1 (ja) |
TW (1) | TW200521122A (ja) |
WO (1) | WO2005009991A1 (ja) |
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WO2014017516A1 (ja) | 2012-07-25 | 2014-01-30 | 株式会社富士薬品 | 4-[5-(ピリジン-4-イル)-1h-1,2,4-トリアゾール-3-イル]ピリジン-2-カルボニトリルの製造方法および中間体 |
WO2014017515A1 (ja) | 2012-07-25 | 2014-01-30 | 株式会社富士薬品 | 4-[5-(ピリジン-4-イル)-1h-1,2,4-トリアゾール-3-イル]ピリジン-2-カルボニトリルの結晶多形およびその製造方法 |
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JPS5373569A (en) * | 1976-12-14 | 1978-06-30 | Mitsubishi Chem Ind Ltd | 4-substituted-2-piperidine carboxylic acid and its ester |
JP2001072664A (ja) * | 1999-09-07 | 2001-03-21 | Mitsubishi Rayon Co Ltd | trans−4−置換−2−ピペリジンカルボニトリル類の製造方法 |
JP2002528447A (ja) * | 1998-10-23 | 2002-09-03 | ダウ・アグロサイエンス・エル・エル・シー | 殺虫性1−(置換ピリジル)−1,2,4−トリアゾール |
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JP3600832B2 (ja) * | 2002-01-28 | 2004-12-15 | 株式会社富士薬品 | 新規1,2,4−トリアゾール系化合物 |
-
2004
- 2004-07-23 EP EP04747845A patent/EP1650204A4/en not_active Withdrawn
- 2004-07-23 KR KR1020067001212A patent/KR20060037373A/ko not_active Application Discontinuation
- 2004-07-23 AU AU2004259582A patent/AU2004259582A1/en not_active Abandoned
- 2004-07-23 CN CNA2004800213229A patent/CN1826335A/zh active Pending
- 2004-07-23 WO PCT/JP2004/010456 patent/WO2005009991A1/ja active Application Filing
- 2004-07-23 JP JP2005512023A patent/JP3779725B2/ja not_active Expired - Fee Related
- 2004-07-23 CA CA002531912A patent/CA2531912A1/en not_active Abandoned
- 2004-07-23 TW TW093122157A patent/TW200521122A/zh unknown
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JPS4946622B1 (ja) * | 1970-09-25 | 1974-12-11 | ||
JPS5024315B1 (ja) * | 1970-09-25 | 1975-08-14 | ||
JPS5025569A (ja) * | 1973-05-21 | 1975-03-18 | ||
JPS5373569A (en) * | 1976-12-14 | 1978-06-30 | Mitsubishi Chem Ind Ltd | 4-substituted-2-piperidine carboxylic acid and its ester |
JP2002528447A (ja) * | 1998-10-23 | 2002-09-03 | ダウ・アグロサイエンス・エル・エル・シー | 殺虫性1−(置換ピリジル)−1,2,4−トリアゾール |
JP2001072664A (ja) * | 1999-09-07 | 2001-03-21 | Mitsubishi Rayon Co Ltd | trans−4−置換−2−ピペリジンカルボニトリル類の製造方法 |
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014017516A1 (ja) | 2012-07-25 | 2014-01-30 | 株式会社富士薬品 | 4-[5-(ピリジン-4-イル)-1h-1,2,4-トリアゾール-3-イル]ピリジン-2-カルボニトリルの製造方法および中間体 |
WO2014017515A1 (ja) | 2012-07-25 | 2014-01-30 | 株式会社富士薬品 | 4-[5-(ピリジン-4-イル)-1h-1,2,4-トリアゾール-3-イル]ピリジン-2-カルボニトリルの結晶多形およびその製造方法 |
US9199970B2 (en) | 2012-07-25 | 2015-12-01 | Fujiyakuhin Co., Ltd. | 4-[5-(pyridin-4-yl)-1H-1,2,4-triazol-3-yl]pyridine-2-carbonitrile crystalline polymorph and production method therefor |
JPWO2014017515A1 (ja) * | 2012-07-25 | 2016-07-11 | 株式会社富士薬品 | 4−[5−(ピリジン−4−イル)−1h−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルの結晶多形およびその製造方法 |
US9428488B2 (en) | 2012-07-25 | 2016-08-30 | Fujiyakuhin Co., Ltd. | Method for producing 4-[5-(pyridin-4-yl)-1H-1,2,4-triazol-3-yl]pyridine-2-carbonitrile, and intermediate thereof |
JP2018510173A (ja) * | 2015-03-30 | 2018-04-12 | クリスタル ファーマテック カンパニー、リミテッドCrystal Pharmatech Co., Ltd. | トピロキソスタットの新規結晶形及びその製造方法 |
Also Published As
Publication number | Publication date |
---|---|
JPWO2005009991A1 (ja) | 2006-09-07 |
EP1650204A4 (en) | 2008-06-18 |
CA2531912A1 (en) | 2005-02-03 |
EP1650204A1 (en) | 2006-04-26 |
JP3779725B2 (ja) | 2006-05-31 |
CN1826335A (zh) | 2006-08-30 |
KR20060037373A (ko) | 2006-05-03 |
TW200521122A (en) | 2005-07-01 |
AU2004259582A1 (en) | 2005-02-03 |
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