WO2015199006A1 - 3-(アルキルスルホニル)ピリジン-2-カルボン酸の製造方法 - Google Patents
3-(アルキルスルホニル)ピリジン-2-カルボン酸の製造方法 Download PDFInfo
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- WO2015199006A1 WO2015199006A1 PCT/JP2015/067827 JP2015067827W WO2015199006A1 WO 2015199006 A1 WO2015199006 A1 WO 2015199006A1 JP 2015067827 W JP2015067827 W JP 2015067827W WO 2015199006 A1 WO2015199006 A1 WO 2015199006A1
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- 0 *C(c1c(*)ccc(*)n1)=O Chemical compound *C(c1c(*)ccc(*)n1)=O 0.000 description 5
- DYKPANQCIFHPMI-UHFFFAOYSA-N O=C(c(nc(cc1)Cl)c1Cl)Cl Chemical compound O=C(c(nc(cc1)Cl)c1Cl)Cl DYKPANQCIFHPMI-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
- C07D213/807—Processes of preparation by oxidation of pyridines or condensed pyridines
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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
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/83—Thioacids; Thioesters; Thioamides; Thioimides
Definitions
- the present invention relates to a method for producing 3- (alkylsulfonyl) pyridine-2-carboxylic acid.
- 3- (Alkylsulfonyl) pyridine-2-carboxylic acid is an important compound as an intermediate for producing pharmaceuticals and agricultural chemicals (for example, WO2013 / 018928), and various production methods are known.
- Journal of Medicinal Chemistry, 1974, Vol. 17, No. 10, page 1065-1071 includes a method for producing 3- (methylthio) pyridine-2-carboxylic acid from 3-aminopicolinic acid, Journal of Medicinal Chemistry, 1977, 20 , No. 4, pages 572-576, 3- (methylthio) pyridine-2-carboxylic acid is converted to methyl ester, oxidized, then hydrolyzed to give 3- (methylsulfonyl) pyridine-2-carboxylic acid.
- a method of manufacturing is described.
- the present invention provides a process for preparing 3- (alkylsulfonyl) pyridine-2-carboxylic acid compounds from 3,6-dihalogenopyridine-2-carboxylic acid.
- a compound represented by the following formula (7) or a salt thereof is represented by the formula (1-S):
- R 1 represents a C1-C8 linear alkyl group
- X represents a halogen atom.
- R 2 SM 2 (2) [Wherein R 2 represents a C1-C8 linear alkyl group, and M 2 represents a hydrogen atom or an alkali metal. ] Is reacted with a compound represented by the formula (3-S)
- R 2 represents the same meaning as described above.
- It can manufacture with the manufacturing method including the process DS which obtains the compound or its salt represented by these.
- R 1 SM 1 (5) [Wherein, R 1 represents a C1-C8 linear alkyl group, and M 1 represents a hydrogen atom or an alkali metal. ] It can also be produced by a process BS comprising a step BS to obtain a compound represented by the formula (1-S) and a production method comprising the above steps AS, CS and DS.
- the C1-C8 linear alkyl group includes a methyl group, an ethyl group, a propyl group, a butyl group, an octyl group, and the like.
- a halogen atom is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
- Alkali metal means lithium, sodium, potassium, cesium and the like.
- R 1 is preferably a C1-C4 linear alkyl group, more preferably a methyl group and an ethyl group. .
- Two X's represent the same atom, preferably a chlorine atom.
- Examples of the compound (1-S) include S-methyl 3,6-dichloropyridine-2-thiocarboxylate, S-ethyl 3,6-dichloropyridine-2-thiocarboxylate, and 3,6-dichloropyridine-2-thiocarboxylic acid.
- R 2 is preferably a C1-C4 linear alkyl group, more preferably a methyl group and an ethyl group, and M 2 is Preferred are a hydrogen atom, sodium and potassium.
- Examples of the compound (2) include alkanethiols such as methanethiol, ethanethiol, propanethiol, butanethiol, and octanethiol: lithium methanethiolate, sodium methanethiolate, potassium methanethiolate, lithium ethanethiolate, sodium ethanethiolate, potassium ethanethiolate, Alkali metal alkane thiolates such as lithium propane thiolate, sodium propane thiolate, potassium propane thiolate, lithium butane thiolate, sodium butane thiolate, potassium butane thiolate, and the like, preferably methane thiol, ethane thiol, sodium methane thiolate, potassium methane thiolate, Sodium ethanethiolate and potassium ethanethiolate.
- alkanethiols such as methanethiol, ethanethiol, propanethio
- Step AS is a step in which compound (1-S) and compound (2) are reacted to obtain a compound represented by formula (3-S) (hereinafter referred to as compound (3-S)).
- methanethiol compounds are alkanethiols such as ethanethiol (2), i.e., the case of using M 2 is a hydrogen atom the compound (2) is carried out usually in the presence of a base.
- Alkali metal hydrides such as lithium hydroxide, sodium hydride and potassium hydride: Alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide: Alkaline earth metal waters such as calcium hydroxide and barium hydroxide Oxides: Alkali metal alcoholates such as lithium methylate, sodium methylate, potassium methylate, lithium ethylate, sodium ethylate, potassium ethylate, lithium tert-butylate, sodium tert-butylate, potassium tert-butylate, etc. .
- Step AS is usually performed in a solvent.
- the solvent include aromatic hydrocarbon solvents such as toluene, xylene, and ethylbenzene, halogenated aromatic hydrocarbon solvents such as monochlorobenzene and o-dichlorobenzene, tetrahydrofuran, and methyl tert-butyl ether.
- Ether solvents such as acetonitrile, nitrile solvents such as acetonitrile and propionitrile, ester solvents such as ethyl acetate and propyl acetate, halogenated hydrocarbon solvents such as dichloromethane and 1,2-dichloroethane, N, N-dimethylformamide, N, N
- amide solvents such as dimethylacetamide and N-methylpyrrolidone, water, and mixed solvents thereof.
- the reaction between the compound (1-S) and the compound (2) is usually carried out by mixing the two. Upon mixing, the compound (2) may be added to the compound (1-S), or the compound (1 Compound (1-S) may be added to 2).
- the compound (1-S) may be added to the mixture of the compound (2) and the base, or the mixture of the compound (2) and the base may be added to the compound (1-S). . Further, a base may be added to the mixture of the compound (1-S) and the compound (2).
- the amount of compound (2) to be used is generally 0.8 to 3.0 mol times, preferably 1.0 to 1.5 mol times relative to compound (1-S).
- the amount of the base to be used is generally 0.8 to 3.0 mol times, preferably 0.9 to 1.2 mol times relative to compound (2).
- phase transfer catalyst When the reaction mixture is separated into an organic layer and an aqueous layer, a phase transfer catalyst may be used.
- the phase transfer catalyst tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydroxide, benzyltrimethylammonium Quaternary ammonium salts such as bromide, benzyltrimethylammonium chloride, benzyltrimethylammonium hydroxide: phosphonium salts such as tetrabutylphosphonium chloride, tetrabutylphosphonium bromide, tetrabutylphosphonium hydroxide, tetraphenylphosphonium bromide, tetraphenylphosphonium chloride, etc. Can be mentioned.
- the amount of the phase transfer catalyst to be used is generally 0.01 to 1.0 mol times, preferably 0.02 to 0.3 mol times relative to compound (2).
- the reaction temperature is usually ⁇ 10 to 100 ° C., preferably 0 to 60 ° C.
- the reaction time varies depending on the reaction temperature, but is usually 1 to 50 hours.
- compound (3-S) can be isolated by ordinary post-treatment. For example, compound (3-S) can be isolated by adding water to the reaction mixture, extracting with an organic solvent, and concentrating the obtained organic layer. The obtained compound (3-S) can be further purified by column chromatography, recrystallization or the like.
- the compound (3-S) include S-methyl 6-chloro-3- (methylthio) pyridine-2-thiocarboxylate, S-ethyl 6-chloro-3- (methylthio) pyridine-2-thiocarboxylate, S-propyl 6-chloro-3- (methylthio) pyridine-2-thiocarboxylate, S-butyl 6-chloro-3- (methylthio) pyridine-2-thiocarboxylate, 6-bromo-3- (methylthio) pyridine-2 -S-methyl thiocarboxylate, S-ethyl 6-bromo-3- (methylthio) pyridine-2-thiocarboxylate, S-propyl 6-bromo-3- (methylthio) pyridine-2-thiocarboxylate, 6-bromo-3 -(Methylthio) pyridine-2-thiocarboxylic acid S-butyl, 6-chloro-3- (ethylthio) pyridine-2
- step CS compound (3-S) is reacted with hydrogen peroxide in the presence of a tungsten catalyst and an acid, and the compound represented by formula (6-S) (hereinafter referred to as compound (6-S)) is described. Is a process of manufacturing.
- Hydrogen peroxide is usually used in an aqueous solution, and its concentration is usually 10 to 70 wt%, preferably 30 to 60 wt%.
- the amount of hydrogen peroxide to be used is generally 3.0 to 10 mol times, preferably 4.0 to 8.0 mol times, more preferably 5.0 to 6.0 mol times with respect to compound (3-S). It is.
- tungsten catalyst examples include tungsten, tungstic acid, sodium tungstate, tungsten oxide, sodium phosphotungstate, silicotungstic acid, etc., preferably sodium tungstate.
- the amount of tungsten catalyst used is usually 0.5 to 10 mol, preferably 1.0 to 5.0 mol, per 100 mol of compound (3-S).
- Examples of the acid include water-soluble acids such as sulfuric acid, methanesulfonic acid, ethanesulfonic acid, nitric acid, and phosphoric acid, and sulfuric acid is preferable.
- the amount of acid used is usually 0.01 to 1 mol times, preferably 0.05 to 0.2 mol times relative to compound (3-S).
- Step CS is usually performed in a solvent, and water or a mixed solvent of water and an organic solvent is used as the solvent.
- the organic solvent include aromatic hydrocarbon solvents such as toluene, xylene and ethylbenzene: halogenated aromatic hydrocarbon solvents such as monochlorobenzene and o-dichlorobenzene: ether solvents such as tetrahydrofuran and methyl tert-butyl ether: acetonitrile, Nitrile solvents such as pionitrile: Ester solvents such as ethyl acetate and propyl acetate: Halogenated hydrocarbon solvents such as dichloromethane and 1,2-dichloroethane: N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone And amide solvents such as Step CS is usually performed by mixing compound (3-S), hydrogen peroxide, tungsten catalyst and acid, and in mixing, the mixture is
- Process CS may be performed in the presence of a sodium salt of ethylenediaminetetraacetic acid.
- the amount used is usually 0.8 to 1.5 mole times the tungsten catalyst.
- the reaction temperature is usually 10 to 100 ° C., preferably 40 to 90 ° C.
- the reaction time varies depending on the reaction temperature, but is usually 1 to 50 hours.
- the compound (6-S) can be obtained by removing excess hydrogen peroxide, performing extraction with an organic solvent, and concentrating the obtained organic layer. Further, an alkali metal salt of compound (6-S) can be obtained by adding an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide to compound (6-S). The alkali metal salt of compound (6-S) can also be isolated by appropriately concentrating and cooling the aqueous alkali metal salt solution of compound (6-S). Compound (6-S) and a salt thereof can be further purified by recrystallization.
- a compound (6-S) aqueous solution of alkali metal salt and an acid such as sulfuric acid or hydrochloric acid are mixed, and the precipitated solid is obtained by filtration, or the mixture is extracted with an organic solvent, and the organic layer is concentrated to give (6-S) can also be isolated.
- Compound (6-S) and salts thereof include 6-chloro-3- (methylsulfonyl) pyridine-2-carboxylic acid, 6-bromo-3- (methylsulfonyl) pyridine-2-carboxylic acid, 6-chloro- 3- (ethylsulfonyl) pyridine-2-carboxylic acid, 6-bromo-3- (ethylsulfonyl) pyridine-2-carboxylic acid, 6-chloro-3- (propylsulfonyl) pyridine-2-carboxylic acid, 6-bromo -3- (propylsulfonyl) pyridine-2-carboxylic acid, 6-chloro-3- (butylsulfonyl) pyridine-2-carboxylic acid, 6-bromo-3- (butylsulfonyl) pyridine-2-carboxylic acid, 6- Chloro-3- (methylsulfonyl) pyridine-2-
- step DS compound (6-S) or a salt thereof is reduced in the presence of a base and a heterogeneous transition metal catalyst, thereby reducing the compound represented by formula (7) (hereinafter referred to as compound (7)). Or a salt thereof.
- Heterogeneous transition metal catalysts include heterogeneous palladium catalysts such as palladium / carbon, palladium / silica, palladium / alumina, palladium / barium sulfate; heterogeneous platinum such as platinum / carbon, platinum / silica, platinum / alumina, etc.
- heterogeneous ruthenium catalyst such as ruthenium / carbon, ruthenium / silica, ruthenium / alumina
- heterogeneous rhodium catalyst such as rhodium / carbon, rhodium / silica, rhodium / alumina
- heterogeneous iridium catalyst such as iridium / carbon
- a heterogeneous osmium catalyst such as osmium / carbon
- a heterogeneous nickel catalyst such as a nickel diatomaceous earth catalyst or a Raney nickel
- a cobalt catalyst such as a Raney cobalt catalyst
- platinum group elements palladium, platinum, ruthenium, and rhodium , Iridium and osmium heterogeneous platinum group Medium is preferably heterogeneous palladium catalyst is more preferable in terms of industrial use, palladium / carbon is most preferred.
- the amount of the heterogeneous catalyst used is usually 0.01 to 5 mol, preferably 0.05 to 0.5 mol, per 100 mol of the compound (6-S).
- the base is not particularly limited as long as it can neutralize the generated hydrogen halide, and alkali metal carbonates such as lithium carbonate, potassium carbonate, and sodium carbonate: alkali metal hydrogen carbonates such as lithium hydrogen carbonate, sodium bicarbonate, and potassium bicarbonate Salt: lithium acetate, sodium acetate, potassium acetate, lithium oxalate, sodium oxalate, potassium oxalate, etc. and alkali metal carboxylate, lithium phosphate, sodium phosphate, potassium phosphate, etc.
- alkali metal phosphate lithium hydrogen phosphate And alkali metal hydrogen phosphates such as sodium hydrogen phosphate and potassium hydrogen phosphate; and alkali metal dihydrogen phosphates such as lithium dihydrogen phosphate, sodium dihydrogen phosphate and potassium dihydrogen phosphate.
- the amount of the base used is usually 0.5 to 5.0 moles, preferably 1.0 to 3.0 moles, relative to compound (6-S).
- the amount of the base used is generally 0.3 to 3 mol times, preferably 0.5 to 1.5 mol, relative to the salt of compound (6-S) Is double.
- a reducing agent such as hydrogen or ammonium formate is used.
- the hydrogen partial pressure is usually 0.01 to 5 MPa, preferably 0.05 to 1 MPa.
- the amount used is usually 0.8 to 5 moles, preferably 1.0 to 3.0 moles, relative to compound (6-S).
- the reduction reaction is usually carried out in a solvent.
- the solvent include water: alcohol solvents such as methanol, ethanol and 2-propanol: aromatic hydrocarbon solvents such as toluene, xylene and ethylbenzene: tetrahydrofuran, methyl tert-butyl ether and the like.
- Ether solvents Ester solvents such as ethyl acetate and propyl acetate: Ketone solvents such as acetone and methyl isobutyl ketone: Amide solvents such as N, N-dimethylformamide, N, N-dimethylacetamide and N-methylpyrrolidone and mixed solvents thereof Can be mentioned.
- the reduction reaction in Step DS is usually performed by mixing the compound (6-S), a base, a heterogeneous transition metal catalyst, and a reducing agent. For example, the compound (6-S), a base, and a heterogeneous mixture are mixed.
- Examples thereof include a method of adding a reducing agent to a mixture of transition gold catalysts and a method of adding compound (6-S) and a reducing agent to a mixture of a base and a heterogeneous transition gold catalyst.
- the reaction temperature is usually 10 to 100 ° C., preferably 20 to 60 ° C.
- the reaction time varies depending on the reaction temperature and hydrogen partial pressure, but is usually 1 to 50 hours.
- the solid content of the catalyst or the like is removed by filtration, and the filtrate is concentrated to obtain the salt of compound (7).
- the compound (7) and salts thereof include 3- (methylsulfonyl) pyridine-2-carboxylic acid, 3- (ethylsulfonyl) pyridine-2-carboxylic acid, 3- (propylsulfonyl) pyridine-2-carboxylic acid Acid, 3- (butylsulfonyl) pyridine-2-carboxylic acid, lithium 3- (methylsulfonyl) pyridine-2-carboxylate, lithium 3- (ethylsulfonyl) pyridine-2-carboxylate, 3- (propylsulfonyl) pyridine Lithium-2-carboxylate, lithium 3- (butylsulfonyl) pyridine-2-carboxylate, sodium 3- (methylsulfonyl) pyridine-2-carboxylate, sodium 3- (ethylsulfonyl) pyridine-2-carboxylate, 3 -(Propylsulfonyl)
- X is preferably a chlorine atom
- Y is preferably a chlorine atom
- Examples of the compound (4) include 3,6-difluoropyridine-2-carboxylic acid chloride, 3,6-difluoropyridine-2-carboxylic acid bromide, 3,6-difluoropyridine-2-carboxylic acid iodide, 3,6 -Dichloropyridine-2-carboxylic acid chloride, 3,6-dichloropyridine-2-carboxylic acid bromide, 3,6-dichloropyridine-2-carboxylic acid iodide, 3,6-dibromopyridine-2-carboxylic acid chloride, 3 , 6-Dibromopyridine-2-carboxylic acid bromide, 3,6-dibromopyridine-2-carboxylic acid iodide, 3,6-diiodopyridine-2-carboxylic acid chloride, 3,6-diiodopyridine-2-carboxylic acid And acid bromide and 3,6-diiodopyridine
- R 1 is preferably a C1-C8 linear alkyl group, more preferably a methyl group or an ethyl group, and M is preferably a hydrogen atom, sodium or potassium.
- Examples of the compound (5) include alkanethiols such as methanethiol, ethanethiol, propanethiol, butanethiol, and octanethiol: lithium methanethiolate, sodium methanethiolate, potassium methanethiolate, lithium ethanethiolate, sodium ethanethiolate, potassium ethanethiolate, Alkali metal alkane thiolates such as lithium propane thiolate, sodium propane thiolate, potassium propane thiolate, lithium butane thiolate, sodium butane thiolate, potassium butane thiolate, and the like, preferably methane thiol, ethane thiol, sodium methane thiolate, potassium methane thiolate Sodium ethanethiolate and potassium ethanethiolate.
- alkanethiols such as methanethiol, ethanethiol, propanethio
- the step BS may be performed in the presence of a base.
- the base include tertiary amines such as pyridine, triethylamine and diisopropylethylamine in addition to the base used in Step AS.
- Preferred bases used in Step BS are tertiary amines such as pyridine, triethylamine, diisopropylethylamine, etc .
- alkali metal hydrides such as sodium hydride and potassium hydride
- alkali metal hydroxides such as sodium hydroxide and potassium hydroxide
- Materials Alkali metal tertiary alcoholates such as lithium tert-butylate, sodium tert-butylate, potassium tert-butylate and the like.
- Step BS is usually performed in a solvent.
- the solvent examples include aromatic hydrocarbon solvents such as toluene, xylene, and ethylbenzene, halogenated aromatic hydrocarbon solvents such as monochlorobenzene and o-dichlorobenzene, tetrahydrofuran, and methyl tert-butyl ether.
- Ether solvents such as acetonitrile, nitrile solvents such as acetonitrile and propionitrile, ester solvents such as ethyl acetate and propyl acetate, halogenated hydrocarbon solvents such as dichloromethane and 1,2-dichloroethane, N, N-dimethylformamide, N, N
- amide solvents such as dimethylacetamide and N-methylpyrrolidone, water, and mixed solvents thereof.
- Step BS is usually performed by mixing compound (4) and compound (5). Upon mixing, compound (4) may be added to compound (5), or compound (4) may be added to compound (5). May be added.
- the compound (4) When using a base, the compound (4) may be added to the mixture of the compound (5) and the base, or the mixture of the compound (5) and the base may be added to the compound (4).
- the mixture of the compound (5) in which M is a hydrogen atom and the alkali metal alcoholate may be concentrated to remove the by-produced alcohol, and then reacted with the compound (4).
- the compound (5) may be added to a mixture of the compound (4) and the base.
- phase transfer catalyst When the reaction mixture is separated into an organic layer and an aqueous layer, a phase transfer catalyst may be used.
- the phase transfer catalyst tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydroxide, benzyltrimethylammonium Quaternary ammonium salts such as bromide, benzyltrimethylammonium chloride, benzyltrimethylammonium hydroxide: phosphonium salts such as tetrabutylphosphonium chloride, tetrabutylphosphonium bromide, tetrabutylphosphonium hydroxide, tetraphenylphosphonium bromide, tetraphenylphosphonium chloride, etc. Can be mentioned.
- the amount of the phase transfer catalyst used is usually 0.01 to 1.0 mol times, preferably 0.02 to 0.3 mol times with respect to the compound (5).
- the reaction temperature is usually ⁇ 10 to 100 ° C., preferably 0 to 60 ° C.
- the reaction time varies depending on the reaction temperature, but is usually 1 to 50 hours.
- the amount of compound (5) to be used is generally 0.8 to 3.0 mol times, preferably 1.0 to 1.5 mol times with respect to compound (4).
- the amount of the base to be used is generally 0.8 to 3.0 mol times, preferably 0.9 to 1.2 mol times relative to compound (5).
- compound (1-S) can be isolated by ordinary post-treatment.
- the compound (1-S) can be isolated by concentrating the reaction mixture or adding water to the reaction mixture, extracting with an organic solvent, and concentrating the obtained organic layer.
- the obtained compound (1-S) can be further purified by column chromatography and recrystallization.
- compound (3-S) can be obtained in one pot without isolating compound (1-S) obtained in step BS.
- a base is usually used to produce compound (3-S) in one pot, and examples of the base include those used in step AS. .
- the base used for one-pot production is preferably an alkali metal hydride such as sodium hydride or potassium hydride: an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide: lithium tert-butylate, sodium tert -Alkali metal tertiary alcoholates such as butyrate, potassium tert-butyrate and the like.
- the amount of compound (5) used is the total of compound (2) and compound (5), and is usually 1.6 to 6 mol times, preferably 2.0 to 3.0 mol times with respect to compound (4). More preferably, it is 2.0 to 2.5 mole times.
- the amount of the base used is usually 0.8 to 3.0 mol times, preferably 0.9 to 1.2 mol times based on the compound (5).
- phase transfer catalyst When the reaction mixture is separated into an organic layer and an aqueous layer, a phase transfer catalyst may be used.
- the phase transfer catalyst tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydroxide, benzyltrimethylammonium Quaternary ammonium salts such as bromide, benzyltrimethylammonium chloride, benzyltrimethylammonium hydroxide: phosphonium salts such as tetrabutylphosphonium chloride, tetrabutylphosphonium bromide, tetrabutylphosphonium hydroxide, tetraphenylphosphonium bromide, tetraphenylphosphonium chloride, etc. Can be mentioned.
- the amount of the phase transfer catalyst to be used is generally 0.01 to 1.0 mol times, preferably 0.02 to 0.3 mol times relative to compound (5).
- the reaction temperature is usually ⁇ 10 to 100 ° C., preferably 0 to 60 ° C.
- the reaction time varies depending on the reaction temperature, but is usually 1 to 50 hours.
- compound (3-S) can be isolated by ordinary post-treatment. For example, compound (3-S) can be isolated by adding water to the reaction mixture, extracting with an organic solvent, and concentrating the obtained organic layer. The obtained compound (3-S) can be further purified by column chromatography and recrystallization.
- the method of the present invention makes it possible to produce compounds such as 3- (alkylsulfonyl) pyridine-2-carboxylic acid that are useful as intermediates for the production of medical and agricultural chemicals.
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Abstract
Description
一方、3-(アルキルチオ)ピリジン-2-カルボン酸を製造する方法としては、3-ハロゲノピリジン-2-カルボン酸とチオール化合物とを反応させて製造する方法が知られている(WO2013/018928)。
本発明によれば、後述の式(7)で表される化合物又はその塩は、式(1-S)
で表される化合物と式(2)
R2SM2 (2)
〔式中、R2はC1~C8の直鎖アルキル基を表し、M2は水素原子又はアルカリ金属を表す。〕
で表される化合物とを反応させ、式(3-S)
で表される化合物又はその塩を得る工程DSを含む製造方法により、製造することができる。
で表される化合物と式(5)
R1SM1 (5)
〔式中、R1はC1~C8の直鎖アルキル基を表し、M1は水素原子又はアルカリ金属を表す。〕
で表される化合物とを反応させ、式(1-S)で表される化合物を得る工程BS、並びに上記の工程AS、工程CS及び工程DSを含む製造方法により、製造することもできる。
C1~C8の直鎖アルキル基とはメチル基、エチル基、プロピル基、ブチル基、オクチル基等である。
ハロゲン原子とはフッ素原子、塩素原子、臭素原子及びヨウ素原子である。
アルカリ金属とは、リチウム、ナトリウム、カリウム、セシウム等を意味する。
式(1-S)で表される化合物(以後、化合物(1-S)と記載する)において、R1は好ましくはC1~C4の直鎖アルキル基、より好ましくはメチル基及びエチル基である。2つのXは同一の原子を表し、好ましくは塩素原子である。化合物(1-S)としては、3,6-ジクロロピリジン-2-チオカルボン酸S-メチル、3,6-ジクロロピリジン-2-チオカルボン酸S-エチル、3,6-ジクロロピリジン-2-チオカルボン酸S-プロピル、3,6-ジクロロピリジン-2-チオカルボン酸S-ブチル、3,6-ジブロモピリジン-2-チオカルボン酸S-メチル、3,6-ジブロモピリジン-2-チオカルボン酸S-エチル、3,6-ジブロモピリジン-2-チオカルボン酸S-プロピル及び3,6-ジブロモピリジン-2-チオカルボン酸S-ブチル等が挙げられる。
式(2)で表される化合物(以後、化合物(2)と記載する)において、R2は好ましくはC1~C4の直鎖アルキル基、より好ましくはメチル基及びエチル基であり、M2は好ましくは水素原子、ナトリウム及びカリウムである。化合物(2)としては、メタンチオール、エタンチオール、プロパンチオール、ブタンチオール、オクタンチオール等のアルカンチオール:リチウムメタンチオラート、ナトリウムメタンチオラート、カリウムメタンチオラート、リチウムエタンチオラート、ナトリウムエタンチオラート、カリウムエタンチオラート、リチウムプロパンチオラート、ナトリウムプロパンチオラート、カリウムプロパンチオラート、リチウムブタンチオラート、ナトリウムブタンチオラート、カリウムブタンチオラート等のアルカリ金属アルカンチオラート等が挙げられ、好ましくはメタンチオール、エタンチオール、ナトリウムメタンチオラート、カリウムメタンチオラート、ナトリウムエタンチオラート及びカリウムエタンチオラートである。
工程ASは、化合物(1-S)と化合物(2)とを反応させ、式(3-S)で表される化合物(以後、化合物(3-S)と記載する)を得る工程である。
工程ASにおいて、メタンチオール、エタンチオール等のアルカンチオールである化合物(2)、即ちM2が水素原子である化合物(2)を用いる場合、通常塩基の存在下に行われ、塩基としては、水素化リチウム、水素化ナトリウム、水素化カリウム等のアルカリ金属水素化物:水酸化リチウム、水酸化ナトリウム、水酸化カリウム等のアルカリ金属水酸化物:水酸化カルシウム、水酸化バリウム等のアルカリ土類金属水酸化物:リチウムメチラート、ナトリウムメチラート、カリウムメチラート、リチウムエチラート、ナトリウムエチラート、カリウムエチラート、リチウムtert-ブチラート、ナトリウムtert-ブチラート、カリウムtert-ブチラート等のアルカリ金属アルコラート等が挙げられる。好ましくは水素化ナトリウム、水素化カリウム、水酸化ナトリウム、水酸化カリウム、ナトリウムメチラート、カリウムメチラート、ナトリウムエチラート、カリウムエチラート、ナトリウムtert-ブチラート及びカリウムtert-ブチラートである。
工程ASは通常溶媒中で行われ、溶媒としては例えばトルエン、キシレン、エチルベンゼン等の芳香族炭化水素溶媒、モノクロロベンゼン、o-ジクロロベンゼン等のハロゲン化芳香族炭化水素溶媒、テトラヒドロフラン、メチルtert-ブチルエーテル等のエーテル溶媒、アセトニトリル、プロピオニトリル等のニトリル溶媒、酢酸エチル、酢酸プロピル等のエステル溶媒、ジクロロメタン、1,2-ジクロロエタン等のハロゲン化炭化水素溶媒、N,N-ジメチルホルムアミド、N,N-ジメチルアセトアミド、N-メチルピロリドン等のアミド溶媒、水及びこれらの混合溶媒が挙げられる。
化合物(2)の使用量は、化合物(1-S)に対して通常0.8~3.0モル倍、好ましくは1.0~1.5モル倍である。
塩基の使用量は、化合物(2)に対して通常0.8~3.0モル倍、好ましくは0.9~1.2モル倍である。
反応温度は通常-10~100℃、好ましくは0~60℃である。反応時間は反応温度により異なるが、通常1~50時間である。
反応終了後は通常の後処理により、化合物(3-S)を単離することができる。例えば、反応混合物に水を加え、有機溶媒で抽出し、得られた有機層を濃縮することにより、化合物(3-S)を単離することができる。得られた化合物(3-S)は、カラムクロマトグラフィー、再結晶等により更に精製することもできる。
工程CSは、化合物(3-S)と過酸化水素とを、タングステン触媒及び酸の存在下で反応させ、式(6-S)で表される化合物(以後、化合物(6-S)と記載する)を製造する工程である。
工程CSは、通常化合物(3-S)、過酸化水素、タングステン触媒及び酸を混合することにより行われ、混合に際しては、化合物(3-S)、タングステン触媒、酸及び水の混合物に過酸化水素を加える方法が一般的である。
工程DSは、化合物(6-S)又はその塩を、塩基及び不均一系遷移金属触媒の存在下で還元することによる、式(7)で表される化合物(以後、化合物(7)と記載する)又はその塩を得る工程である。
ギ酸アンモニウムを使用する場合、その使用量は、化合物(6-S)に対して通常0.8~5モル倍、好ましくは1.0~3.0モル倍である。
還元反応は、通常溶媒中で行われ、溶媒としては例えば水:メタノール、エタノール、2-プロパノール等のアルコール溶媒:トルエン、キシレン、エチルベンゼン等の芳香族炭化水素溶媒:テトラヒドロフラン、メチルtert-ブチルエーテル等のエーテル溶媒:酢酸エチル、酢酸プロピル等のエステル溶媒:アセトン、メチルイソブチルケトン等のケトン溶媒:N,N-ジメチルホルムアミド、N,N-ジメチルアセトアミド、N-メチルピロリドン等のアミド溶媒及びその混合溶媒が挙げられる。
工程DSの還元反応は、通常化合物(6-S)、塩基、不均一遷移金属触媒及び還元剤を混合することにより行われ、混合に際しては、例えば、化合物(6-S)、塩基及び不均一遷移金触媒の混合物に還元剤を加える方法、塩基と不均一遷移金触媒との混合物に化合物(6-S)と還元剤をそれぞれ加える方法が挙げられる。
反応温度は通常10~100℃、好ましくは20~60℃である。反応時間は反応温度、水素分圧により異なるが、通常1~50時間である。
反応終了後、触媒等の固形分を濾過により除去し、濾液を濃縮することにより、化合物(7)の塩を得ることができる。
該塩に塩酸、硫酸等の酸水溶液を加え析出した固体を、濾別することにより、又は該塩に塩酸、硫酸等の酸水溶液を加え、有機溶媒で抽出し、得られた有機層を濃縮することにより、化合物(7)を単離することができる。化合物(7)及びその塩は、再結晶により更に精製することもできる。
化合物(7)及びその塩の具体例としては、3-(メチルスルホニル)ピリジン-2-カルボン酸、3-(エチルスルホニル)ピリジン-2-カルボン酸、3-(プロピルスルホニル)ピリジン-2-カルボン酸、3-(ブチルスルホニル)ピリジン-2-カルボン酸、3-(メチルスルホニル)ピリジン-2-カルボン酸リチウム、3-(エチルスルホニル)ピリジン-2-カルボン酸リチウム、3-(プロピルスルホニル)ピリジン-2-カルボン酸リチウム、3-(ブチルスルホニル)ピリジン-2-カルボン酸リチウム、3-(メチルスルホニル)ピリジン-2-カルボン酸ナトリウム、3-(エチルスルホニル)ピリジン-2-カルボン酸ナトリウム、3-(プロピルスルホニル)ピリジン-2-カルボン酸ナトリウム、3-(ブチルスルホニル)ピリジン-2-カルボン酸ナトリウム、3-(メチルスルホニル)ピリジン-2-カルボン酸カリウム、3-(エチルスルホニル)ピリジン-2-カルボン酸カリウム、3-(プロピルスルホニル)ピリジン-2-カルボン酸カリウム及び3-(ブチルスルホニル)ピリジン-2-カルボン酸カリウムが挙げられる。
化合物(1-S)は、式(4)で表される化合物(以後、化合物(4)と記載する)と式(5)で表される化合物(以後、化合物(5)と記載する)とを反応させる工程BSにより製造することができる。
化合物(4)は、例えば対応するカルボン酸を酸ハロゲン化物等でハロゲン化することにより製造することができる。
工程BSは通常溶媒中で行われ、溶媒としては例えばトルエン、キシレン、エチルベンゼン等の芳香族炭化水素溶媒、モノクロロベンゼン、o-ジクロロベンゼン等のハロゲン化芳香族炭化水素溶媒、テトラヒドロフラン、メチルtert-ブチルエーテル等のエーテル溶媒、アセトニトリル、プロピオニトリル等のニトリル溶媒、酢酸エチル、酢酸プロピル等のエステル溶媒、ジクロロメタン、1,2-ジクロロエタン等のハロゲン化炭化水素溶媒、N,N-ジメチルホルムアミド、N,N-ジメチルアセトアミド、N-メチルピロリドン等のアミド溶媒、水及びこれらの混合溶媒が挙げられる。
反応終了後、通常の後処理により化合物(1-S)を単離することができる。例えば、反応混合物を濃縮することにより、又は反応混合物に水を加え、有機溶媒で抽出し、得られた有機層を濃縮することにより、化合物(1-S)を単離することができる。得られた化合物(1-S)を更に、カラムクロマトグラフィー、再結晶により精製することもできる。
化合物(5)と化合物(2)とが同一である場合、工程BSにより得られた化合物(1-S)を単離することなく、ワンポットで化合物(3-S)を得ることができる。
反応温度は通常-10~100℃、好ましくは0~60℃である。反応時間は反応温度により異なるが、通常1~50時間である。
反応終了後、通常の後処理により化合物(3-S)を単離することができる。例えば、反応混合物に水を加え、有機溶媒で抽出し、得られた有機層を濃縮することにより、化合物(3-S)を単離することができる。得られた化合物(3-S)は、カラムクロマトグラフィー、再結晶により更に精製することもできる。
参考例2
実施例1
1H-NMR(DMSO-d6)δ:1.25-1.29(3H,t)、2.95-3.00(2H,q)、7.84-7.88(1H,d)、8.20-8.22(1H,d)
実施例2
実施例3
1H-NMR(CDCl3)δ:8.47(1H,d),7.73(1H,d),3.70(2H,q),1.35(3H,t)
実施例4
実施例5
1H-NMR(DMSO-d6)δ:1.05-1.09(3H,t)、3.69-3.75(2H,q)、7.51-7.53(1H,d)、8.09-8.11(1H,d)
実施例6
実施例7
1H-NMR(DMSO-d6)δ:1.03-1.07(3H,t)、3.70-3.75(2H,q)、7.38-7.41(1H,m)、8.06-8.09(1H,m)、8.61-8.64(1H,m)
実施例8
1H-NMR(DMSO-d6)δ:1.15-1.19(3H,t)、3.49-3.55(2H,q)、7.79-7.83(1H,m)、8.35-8.38(1H,m)、8.90-8.92(1H,m)
実施例9
1H-NMR(DMSO-d6)δ:1.22-1.29(6H,m)、2.89-2.94(2H,q)、2.99-3.05(2H,q)、7.72-7.74(1H,m)、7.98-8.00(1H,m)
実施例10
比較例1
Claims (8)
- 式(1-S)
〔式中、R1はC1~C8の直鎖アルキル基を表し、Xはハロゲン原子を表す。〕
で表される化合物と式(2)
R2SM2 (2)
〔式中、R2はC1~C8の直鎖アルキル基を表し、M2は水素原子又はアルカリ金属を表す。〕
で表される化合物とを反応させ、式(3-S)
〔式中、R1、R2及びXは前記と同じ意味を表す。〕
で表される化合物を得る工程、
式(3-S)で表される化合物と過酸化水素とを、タングステン触媒及び酸の存在下で反応させ、式(6-S)
〔式中、X及びR2は前記と同じ意味を表す。〕
で表される化合物又はその塩を得る工程、及び
式(6-S)で表される化合物又はその塩を、塩基及び不均一系遷移金属触媒の存在下で還元する、式(7)
〔式中、R2は前記と同じ意味を表す。〕
で表される化合物又はその塩を得る工程を含む、式(7)で表される化合物又はその塩の製造方法。 - 式(4)
〔式中、Xはハロゲン原子を表し、Yはハロゲン原子を表す。〕
で表される化合物と式(5)
R1SM1 (5)
〔式中、R1はC1~C8の直鎖アルキル基を表し、M1は水素原子又はアルカリ金属を表す。〕
で表される化合物とを反応させ、式(1-S)
〔式中、R1及びXは前記と同じ意味を表す。〕
で表される化合物を得る工程、
式(1-S)で表される化合物と式(2)
R2SM2 (2)
〔式中、R2はC1~C8の直鎖アルキル基を表し、M2は水素原子又はアルカリ金属を表す。〕
で表される化合物とを反応させ、式(3-S)
〔式中、R1、R2及びXは前記と同じ意味を表す。〕
で表される化合物を得る工程、
式(3-S)で表される化合物と過酸化水素とを、タングステン触媒及び酸の存在下で反応させ、式(6-S)
〔式中、X及びR2は前記と同じ意味を表す。〕
で表される化合物を得る工程、及び
式(6-S)で表される化合物又はその塩を、塩基及び不均一系遷移金属触媒の存在下で還元する、式(7)
〔式中、R2は前記と同じ意味を表す。〕
で表される化合物又はその塩を得る工程を含む、式(7)で表される化合物又はその塩の製造方法。 - 式(1-S)
〔式中、R1はC1~C8の直鎖アルキル基を表し、Xはハロゲン原子を表す。〕
で表される化合物と式(2)
R2SM2 (2)
〔式中、R2はC1~C8の直鎖アルキル基を表し、M2は水素原子又はアルカリ金属を表す。〕
で表される化合物とを反応させ、式(3-S)
〔式中、R1、R2及びXは前記と同じ意味を表す。〕
で表される化合物を得る工程、及び
式(3-S)で表される化合物と過酸化水素とを、タングステン触媒及び酸の存在下で反応させ、式(6-S)
〔式中、X及びR2は前記と同じ意味を表す。〕
で表される化合物又はその塩を得る工程を含む、式(6-S)で表される化合物又はその塩の製造方法。 - 式(4)
〔式中、Xはハロゲン原子を表し、Yはハロゲン原子を表す。〕
で表される化合物と式(5)
R1SM1 (5)
〔式中、R1はC1~C8の直鎖アルキル基を表し、M1は水素原子又はアルカリ金属を表す。〕
で表される化合物とを反応させ、式(1-S)
〔式中、R1及びXは前記と同じ意味を表す。〕
で表される化合物を得る工程、
式(1-S)で表される化合物と式(2)
R2SM2 (2)
〔式中、R2はC1~C8の直鎖アルキル基を表し、M2は水素原子又はアルカリ金属を表す。〕
で表される化合物とを反応させ、式(3-S)
〔式中、R1、R2及びXは前記と同じ意味を表す。〕
で表される化合物を得る工程、及び
式(3-S)で表される化合物と過酸化水素とを、タングステン触媒及び酸の存在下で反応させ、式(6-S)
〔式中、X及びR2は前記と同じ意味を表す。〕
で表される化合物を得る工程を含む、式(6-S)で表される化合物又はその塩の製造方法。 - 式(4)
〔式中、Xはハロゲン原子を表し、Yはハロゲン原子を表す。〕
で表される化合物と式(5)
R1SM1 (5)
〔式中、R1はC1~C8の直鎖アルキル基を表し、M1は水素原子又はアルカリ金属を表す。〕
で表される化合物とを反応させ、式(1-S)
〔式中、R1及びXは前記と同じ意味を表す。〕
で表される化合物を得る工程、及び
式(1-S)で表される化合物と式(2)
R2SM2 (2)
〔式中、R2はC1~C8の直鎖アルキル基を表し、M2は水素原子又はアルカリ金属を表す。〕
で表される化合物とを反応させ、式(3-S)
〔式中、R1、R2及びXは前記と同じ意味を表す。〕
で表される化合物を得る工程を含む、式(3-S)で表される化合物の製造方法。
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EP15811654.1A EP3162795B1 (en) | 2014-06-26 | 2015-06-22 | Method for manufacturing 3-(alkyl sulfonyl)pyridine-2-carboxylic acid |
CN201580033287.0A CN106660958B (zh) | 2014-06-26 | 2015-06-22 | 3-(烷基磺酰基)吡啶-2-羧酸的制造方法 |
US15/318,551 US9815786B2 (en) | 2014-06-26 | 2015-06-22 | Method for manufacturing 3-(alkylsulfonyl)pyridine-2-carboxylic acid |
RU2017101814A RU2017101814A (ru) | 2014-06-26 | 2015-06-22 | Способ получения 3-(алкилсульфонил)пиридин-2-карбоновой кислоты |
JP2016529561A JP6528772B2 (ja) | 2014-06-26 | 2015-06-22 | 3−(アルキルスルホニル)ピリジン−2−カルボン酸の製造方法 |
AU2015281846A AU2015281846B2 (en) | 2014-06-26 | 2015-06-22 | Method for manufacturing 3-(alkyl sulfonyl)pyridine-2-carboxylic acid |
BR112016029074A BR112016029074A2 (pt) | 2014-06-26 | 2015-06-22 | método para a fabricação de ácido 3-(alquil sulfonil)piridina-2-carboxílico |
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EP (1) | EP3162795B1 (ja) |
JP (2) | JP6528772B2 (ja) |
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CN (2) | CN106458907B (ja) |
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CH657124A5 (en) * | 1983-08-10 | 1986-08-15 | Lonza Ag | 3-Chloroisocinchomeronoyl chloride and a process for its preparation |
JP2009529577A (ja) * | 2006-03-10 | 2009-08-20 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 可溶性エポキシドヒドロラーゼインヒビター及びその使用方法 |
JP2014005263A (ja) * | 2011-08-04 | 2014-01-16 | Sumitomo Chemical Co Ltd | 縮合複素環化合物及びその有害生物防除用途 |
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US4558134A (en) * | 1983-01-03 | 1985-12-10 | The Dow Chemical Company | Certain phenoxy-pyridine-carbonitriles having antiviral activity |
IL91083A (en) * | 1988-07-25 | 1993-04-04 | Ciba Geigy | Cyclohexanedione derivatives, their preparation and their use as herbicides |
AU2006275699A1 (en) * | 2005-08-02 | 2007-02-08 | Merck Sharp & Dohme Corp. | N-(pyridin-4-yl)-2-phenylbutanamides as androgen receptor modulators |
MX370943B (es) | 2012-12-27 | 2020-01-10 | Sumitomo Chemical Co | Compuestos de oxazol fusionados y uso de los mismos para el control de plagas. |
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CH657124A5 (en) * | 1983-08-10 | 1986-08-15 | Lonza Ag | 3-Chloroisocinchomeronoyl chloride and a process for its preparation |
JP2009529577A (ja) * | 2006-03-10 | 2009-08-20 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 可溶性エポキシドヒドロラーゼインヒビター及びその使用方法 |
JP2014005263A (ja) * | 2011-08-04 | 2014-01-16 | Sumitomo Chemical Co Ltd | 縮合複素環化合物及びその有害生物防除用途 |
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BLANK B. ET AL.: "Mercaptopyridinecarboxylic Acids, Synthesis and Hypoglycemic Activity", JOURNAL OF MEDICINAL CHEMISTRY, vol. 17, no. 10, 1974, pages 1065 - 1071, XP002158204, ISSN: 0022-2623 * |
See also references of EP3162795A4 * |
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JPWO2015199006A1 (ja) | 2017-04-20 |
KR20170023963A (ko) | 2017-03-06 |
US9815786B2 (en) | 2017-11-14 |
US9850209B2 (en) | 2017-12-26 |
TWI659020B (zh) | 2019-05-11 |
DE112015003036T5 (de) | 2017-03-16 |
RU2017101814A (ru) | 2018-08-02 |
TW201605803A (zh) | 2016-02-16 |
CN106458907A (zh) | 2017-02-22 |
US20170129859A1 (en) | 2017-05-11 |
EP3162795A4 (en) | 2018-02-28 |
EP3162795A1 (en) | 2017-05-03 |
BR112016029074A2 (pt) | 2017-08-22 |
JPWO2015199007A1 (ja) | 2017-04-20 |
AU2015281846B2 (en) | 2019-08-01 |
CN106660958A (zh) | 2017-05-10 |
IL249296B (en) | 2019-11-28 |
IL249296A0 (en) | 2017-02-28 |
JP6500898B2 (ja) | 2019-04-17 |
KR102332262B1 (ko) | 2021-11-26 |
CN106660958B (zh) | 2019-04-12 |
WO2015199007A1 (ja) | 2015-12-30 |
RU2017101814A3 (ja) | 2019-01-15 |
US20170166529A1 (en) | 2017-06-15 |
AU2015281846A1 (en) | 2017-02-02 |
EP3162795B1 (en) | 2019-07-31 |
JP6528772B2 (ja) | 2019-06-12 |
CN106458907B (zh) | 2018-12-11 |
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