WO2016007532A1 - Process for the preparation of 3-hydroxypicolinic acids - Google Patents
Process for the preparation of 3-hydroxypicolinic acids Download PDFInfo
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- WO2016007532A1 WO2016007532A1 PCT/US2015/039411 US2015039411W WO2016007532A1 WO 2016007532 A1 WO2016007532 A1 WO 2016007532A1 US 2015039411 W US2015039411 W US 2015039411W WO 2016007532 A1 WO2016007532 A1 WO 2016007532A1
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- Prior art keywords
- formula
- compound
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- acid
- alkyl
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- 238000000034 method Methods 0.000 title claims description 27
- 238000002360 preparation method Methods 0.000 title claims description 14
- 150000004811 3-hydroxy picolinic acids Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 53
- 239000000203 mixture Substances 0.000 claims description 36
- 239000002253 acid Substances 0.000 claims description 33
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 11
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 8
- 239000002841 Lewis acid Substances 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 150000007517 lewis acids Chemical class 0.000 claims description 8
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical group [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- 229910052751 metal Inorganic materials 0.000 claims 1
- 229910052725 zinc Inorganic materials 0.000 claims 1
- 239000011701 zinc Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 9
- IQWAGONEJKBWSG-UHFFFAOYSA-N OC(=O)C1=NC(Br)=CC(Br)=C1O Chemical class OC(=O)C1=NC(Br)=CC(Br)=C1O IQWAGONEJKBWSG-UHFFFAOYSA-N 0.000 abstract description 2
- 238000006462 rearrangement reaction Methods 0.000 abstract description 2
- WCQHGWNBRBJIPT-UHFFFAOYSA-N furan-2-yl 2-aminoacetate Chemical class NCC(=O)OC1=CC=CO1 WCQHGWNBRBJIPT-UHFFFAOYSA-N 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- -1 2-substituted furans Chemical class 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 19
- 239000002904 solvent Substances 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 10
- 238000000746 purification Methods 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
- 238000002955 isolation Methods 0.000 description 8
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 5
- GTHKCVOXARUIHX-UHFFFAOYSA-N methyl 2-amino-2-(furan-2-yl)acetate hydrobromide Chemical compound Br.COC(=O)C(N)c1ccco1 GTHKCVOXARUIHX-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 0 *c1nc(Br)cc(Br)c1O Chemical compound *c1nc(Br)cc(Br)c1O 0.000 description 4
- VQKFNUFAXTZWDK-UHFFFAOYSA-N 2-Methylfuran Chemical compound CC1=CC=CO1 VQKFNUFAXTZWDK-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- JSSXJYKVYAICJK-UHFFFAOYSA-N methyl 2-(furan-2-yl)-2-(phenylmethoxycarbonylamino)acetate Chemical compound C=1C=COC=1C(C(=O)OC)NC(=O)OCC1=CC=CC=C1 JSSXJYKVYAICJK-UHFFFAOYSA-N 0.000 description 4
- FEHASYZONKCPOM-UHFFFAOYSA-N methyl 2-amino-2-(furan-2-yl)acetate Chemical compound COC(=O)C(N)C1=CC=CO1 FEHASYZONKCPOM-UHFFFAOYSA-N 0.000 description 4
- 239000012047 saturated solution Substances 0.000 description 4
- ZNQCEVIJOQZWLO-SOFGYWHQSA-N (2e)-2-(furan-2-yl)-2-methoxyiminoacetic acid Chemical compound CO\N=C(\C(O)=O)C1=CC=CO1 ZNQCEVIJOQZWLO-SOFGYWHQSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- IXVPCJUAKDVYKX-UHFFFAOYSA-N 2-(furan-2-yl)-2-oxoacetic acid Chemical compound OC(=O)C(=O)C1=CC=CO1 IXVPCJUAKDVYKX-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- JWBOGZUIBMPVTM-UHFFFAOYSA-N methyl 2-(furan-2-yl)-2-methoxyiminoacetate Chemical compound CON=C(C(=O)OC)C1=CC=CO1 JWBOGZUIBMPVTM-UHFFFAOYSA-N 0.000 description 3
- WNFLHCVLPYFOGW-UHFFFAOYSA-N methyl 4,6-dibromo-3-hydroxypyridine-2-carboxylate Chemical compound COC(=O)C1=NC(Br)=CC(Br)=C1O WNFLHCVLPYFOGW-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 229940044613 1-propanol Drugs 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 239000005456 alcohol based solvent Substances 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 238000001311 chemical methods and process Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- ZNQCEVIJOQZWLO-UHFFFAOYSA-N 2-(furan-2-yl)-2-methoxyiminoacetic acid Chemical compound CON=C(C(O)=O)C1=CC=CO1 ZNQCEVIJOQZWLO-UHFFFAOYSA-N 0.000 description 1
- VIHUZJYFQOEUMI-UHFFFAOYSA-N 3-Hydroxypicolinamide Chemical class NC(=O)C1=NC=CC=C1O VIHUZJYFQOEUMI-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- NNBQAZBSJUATDO-UHFFFAOYSA-N methyl 2-methoxy-2-(phenylmethoxycarbonylamino)acetate Chemical compound COC(=O)C(OC)NC(=O)OCC1=CC=CC=C1 NNBQAZBSJUATDO-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- RIBFXMJCUYXJDZ-UHFFFAOYSA-N propanoyl bromide Chemical compound CCC(Br)=O RIBFXMJCUYXJDZ-UHFFFAOYSA-N 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000010963 scalable process Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Definitions
- the present disclosure concerns a process for the preparation of 4-alkoxy-3- hydroxypicolinic acids. More particularly, the present disclosure concerns a process for the preparation of 4-alkoxy-3-hydroxypicolinic acids from 2-substituted furans.
- the present disclosure concerns a process for the preparation of a compound of Formula A wherein R 2 is a C 1 -C4 alkyl.
- the compound of Formula A is useful in processes to prepare 4-alkoxy-3- hydroxypicolinic acids of Formula
- R 1 is a C 1 -C3 alkyl.
- the compound of Formula A is prepared in a process that comprises the following steps: a) creating a mixture by adding a brominating agent, a base and water to the compound of Formula B
- the compound of Formula B is prepared in a process that comprises the following steps: a) creating a first mixture by combining together an O-alkylhydroxylamine hydrohalide salt of the Formula I R 3 ⁇ NH 2 HX
- R 3 is a C1-C4 alkyl
- R 2 and R 3 are independently a C1-C4 alkyl; e) adding a reducing agent to the compound of Formula E to form a third mixture; f) isolating a compound of Formula F from the third mixture.
- R 2 is a C1-C4 alkyl
- the compound of Formula B may also be prepared in a process that comprises the following steps: a) creating a first mixture by combining together furan, a Lewis acid and the compound of Formula G
- R 2 is a C1-C4 alkyl and R 4 is an acid cleavable group
- the Lewis acid used in the process is boron trifluoride etherate.
- the acid cleavable group is a benzyl group.
- the strong acid used in the process is at least one acid selected from the group consisting of hydrochloric acid and hydrobromic acid.
- Another aspect of the present disclosure is a novel intermediate produced in the present process, viz. , the compound consisting of : wherein R 2 is a C1-C4 alkyl.
- isolated means to partially or completely remove the desired product from the other components of a finished chemical process mixture using standard methods such as, but not limited to, filtration, extraction, distillation, crystallization, centrifugation, trituration, liquid-liquid phase separation or other methods known to those of ordinary skill in the art.
- the isolated product may have a purity that ranges from ⁇ 50% to > 50%, and may be purified to a higher purity level using standard purification methods.
- the isolated product may also be used in a subsequent process step with or without purification.
- Cyano(furan-2-yl)methanaminium halide salts of Formula la have been prepared and used as intermediates in the preparation of 3-hydroxypicolinonitriles and 3-hydroxy- picolinoamides of Formula lb as described in ⁇ cto Chem. Scand. 19 (1965), pg. 1 147-1152,
- 4,6-dibromo-3-hydroxypicolinate esters of Formula A are prepared from alkyl 2-amino-2-(furan-2-yl)acetate hydrohalide salts of Formula B in one chemical step by use of a bromination-rearrangement reaction.
- the starting furan compound of Formula B as either the HC1 or HBr salt and where R 2 represents a C1-C4 alkyl, is treated with a suitable brominating agent such as bromine, l,3-dibromo-5,5-dimethylhydantoin or N- bromosuccinimide.
- the reaction is preferably conducted using about 4 molar equivalents of bromine. It may be convenient to use an excess of the brominating agent such as a 5%,
- a base is used in the reaction and may be selected from sodium acetate or potassium acetate and the like.
- the reaction is preferably carried out in a protic solvent or reaction medium such as water, or mixtures of water and an alcohol such as, methanol or ethanol.
- the temperature at which the reaction is conducted is between about 0 °C and about 10 °C, preferably between about 0 °C and about 5 °C.
- the reaction mixture is allowed to warm to room temperature and stir there for 15-48 hours. After the reaction is complete, the desired product is recovered by employing standard isolation and purification techniques.
- the alkyl 2-amino-2-(furan-2-yl)acetate hydrohalide salt of Formula B may be prepared by the two chemical processes shown in Scheme 1.
- Path A 2-(furan-2-yl)-2- oxoacetic acid (Formula C) is first converted into the O-alkyl oxime ester of Formula E (chemical steps a and b), as described in Chemical Research in Toxicology, 24(5) 706-717 (2011) and in PCT Int. Application 20051 11001 (2005), and then E is converted into the halide salt of Formula B (chemical steps c and d).
- Path B the alkyl 2-methoxy-2-( - carboxyalkylamino)acetate of
- the O-alkyl oxime ester of Formula E is prepared (chemical steps a and b) by first combining together an O-alkyl-hydroxylamine hydrohalide salt, 2-(furan-2-yl)-2-oxoacetic acid (Formula C), a base and a solvent, and heating the resulting mixture to produce the oxime acid of Formula D.
- O-alkyl- hydroxylamine hydrohalide salt R 3 is a C 1 -C 4 alkyl
- Suitable bases include trialkylamines, alkali metal carbonates such as sodium carbonate or potassium carbonate, and the like.
- Suitable solvents include alcohols such as methanol, ethanol or 2-propanol.
- the present reaction is typically conducted with agitation sufficient to maintain an essentially uniform mixture of the reactants and generally requires from about 1 to about 10 hours, preferably
- the O-alkyl oxime acid of Formula D is then converted into the ester of Formula E by esterification in an alcohol solvent in the presence of an acid or an acid- forming compound.
- Suitable alcohol solvents include C1-C4 alcohols such as, for example, methanol, ethanol, 1- propanol and 1-butanol.
- Suitable acids include strong acids such as anhydrous hydrochloric acid, sulfuric acid or p-toluenesulfonic acid, and suitable acid- forming compounds include carboxylic acid halides such as acetyl chloride, acetyl bromide, propionyl chloride or propionyl bromide, and the like.
- From 0.01 to about 2.0 molar equivalents of the acid or acid forming compound may be used.
- the reaction is usually conducted at between about 25 °C and about 85 °C, preferably between about 45 °C and about 65 °C for a period of about 8 to about 48 hours, preferably for about 12 to about 24 hours.
- the oxime ester of Formula E is recovered by employing standard isolation and purification techniques.
- the O-alkyl oxime ester of Formula E is then converted to the aminoester of Formula F by reduction with zinc dust (chemical step c).
- This reaction is normally conducted in an alcohol solvent containing 50% aqueous formic acid. Suitable volume ratios of the alcohol solvent to the 50% aqueous formic acid are from about 4: 1 to about 1 : 1, preferably from about 2: 1 to about 1 : 1.
- Suitable alcohol solvents include C 1 -C 4 alcohols such as, for example, methanol, ethanol, 1-propanol and 1-butanol, preferably, methanol may be used.
- Aminoester F is then converted to the halide salt of Formula B by treatment with a strong acid such as hydrochloric acid, hydrobromic acid or sulfuric acid.
- a strong acid such as hydrochloric acid, hydrobromic acid or sulfuric acid.
- From about 2 to about 6 molar equivalents of the strong acid may be used and may be added to a solution of aminoester F in a water immiscible solvent such as diethyl ether, methyl t-butyl ether, 2- methyl furan, dioxane, and the like.
- the strong acid is normally used in an anhydrous form such as a solution in a non-aqueous solvent such as, for example, acetic acid or dioxane.
- the strong acid may also be added to the process in the form of a gas or a neat liquid.
- the strong acid is normally added to aminoester F at from about 0 °C to about room temperature, and the resulting mixture then conducted for about 0.5 to about 2.0
- the 2-methoxyaminoacid derivative of Formula G is coupled with furan in the presence of a Lewis acid to provide the 2-substituted furan of Formula H.
- the compound of Formula G wherein R 2 is a C 1 -C4 alkyl and R 4 is an acid cleavable group selected from allyl, benzyl or a substituted allyl or benzyl group, is placed in a solvent and then treated at room temperature with the Lewis acid, followed immediately by the addition of furan.
- Suitable solvents for use in this reaction include diethyl ether, methyl t- butyl ether, 2-methyl furan, dioxane, and the like.
- Suitable Lewis acids include boron trifluoride etherate, aluminum trichloride, tin tetrachloride, and the like. Relative to compound G, from about 1.0-2.0, preferably from about 1.2- 1.7, molar equivalents of the Lewis acid and from about 2.0-6.0, preferably from about 3.0-5.0, molar equivalents of furan are typically used in this coupling reaction. The reaction is typically conducted for about 10 hours to about 48 hours, preferably for about 18 to about 32 hours at room temperature. After the reaction is complete, the 2-substituted furan of Formula H is recovered by employing standard isolation and purification techniques.
- the compound of Formula H is converted to the compound of Formula B by treatment with a strong acid, such as, hydrochloric acid, hydrobromic acid or sulfuric acid, at room temperature in a polar, carboxylic acid solvent such as acetic acid, propionic acid, and the like. From about 2.0 to about 7.0, preferably from about 4.0 to about 6.0, molar equivalents of the strong acid may be used.
- the reaction is conducted for about 0.25 to about 5.0 hours, preferably for about 0.5 to about 2 hours at room temperature.
- the 2-substituted furan of Formula B is recovered by employing standard isolation and purification techniques.
- Example 2a The crude 2-(furan-2-yl)-2-(methoxyimino)acetic acid (Example 2a) was dissolved in 100 mL of MeOH and was added to a solution of acetyl chloride (3.82 ml, 53.5 mmol) in 50 mL of MeOH. After refluxing for 16 hr, solvent was removed on the rotary evaporator and the crude product was added to 100 mL EtOAc and 20 mL of water.
- Example 2c The crude methyl 2-amino-2-(furan-2-yl)acetate (Example 2c) was dissolved in 350 mL of anhydrous ether and with rapid magnetic stirring, 10 mL of 33 %wt HBr in acetic acid was added slowly by syringe. After stirring for 30 min. filtration followed by air drying gave methyl 2-amino-2-(furan-2-yl)acetate hydrobromide (12.35 g, 51.8 mmol, 54.2 % yield) as an off-white solid: Mp 141-142 ° ' ⁇ C. IT NMR (400 MHz, DMSO-d6) ⁇ 8.84 (s, 2 ⁇ ), 7.81 (dd, J
Abstract
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ES15819477T ES2726927T3 (en) | 2014-07-08 | 2015-07-07 | Process for the preparation of 3-hydroxypicolinic acids |
KR1020177000111A KR102418462B1 (en) | 2014-07-08 | 2015-07-07 | Process for the preparation of 3-hydroxypicolinic acids |
JP2017500033A JP6560335B2 (en) | 2014-07-08 | 2015-07-07 | Method for producing 3-hydroxypicolinic acid |
EP15819477.9A EP3166928B1 (en) | 2014-07-08 | 2015-07-07 | Process for the preparation of 3-hydroxypicolinic acids |
CA2954268A CA2954268C (en) | 2014-07-08 | 2015-07-07 | Process for the preparation of 3-hydroxypicolinic acids |
BR112016030604A BR112016030604B8 (en) | 2014-07-08 | 2015-07-07 | PROCESS FOR PREPARATION OF 3- HYDROXYPICOLINIC ACIDS |
MX2016017124A MX2016017124A (en) | 2014-07-08 | 2015-07-07 | Process for the preparation of 3-hydroxypicolinic acids. |
CN201580036348.9A CN106660959B (en) | 2014-07-08 | 2015-07-07 | The preparation method of 3- hydroxy-picolinic acid |
IL249794A IL249794B (en) | 2014-07-08 | 2016-12-27 | Process for the preparation of 3-hydroxypicolinic acids |
ZA2017/00034A ZA201700034B (en) | 2014-07-08 | 2017-01-03 | Process for the preparation of 3-hydroxypicolinic acids |
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US10403145B2 (en) * | 2017-01-19 | 2019-09-03 | Ford Global Technologies, Llc | Collison mitigation and avoidance |
JP2020161992A (en) | 2019-03-27 | 2020-10-01 | ソニーセミコンダクタソリューションズ株式会社 | Imaging system and object recognition system |
WO2024018354A1 (en) | 2022-07-18 | 2024-01-25 | Pi Industries Ltd. | A process for the synthesis of 4-alkoxy-3-hydroxypicolinic acids and intermediates thereof |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6521622B1 (en) * | 1999-07-20 | 2003-02-18 | Dow Agrosciences Llc | Fungicidal heterocyclic aromatic amides and their compositions, methods of use and preparation |
Family Cites Families (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3170401D1 (en) | 1980-07-28 | 1985-06-13 | Ciba Geigy Ag | Triazoline derivatives and processes for their preparation |
ATE24504T1 (en) | 1981-03-19 | 1987-01-15 | Ici Plc | AMIDE DERIVATIVES, PROCESS FOR THEIR MANUFACTURE, THEIR USE AS THE FUNGICIDES AND THE PESTICIDES THEY CONTAIN. |
GB9524104D0 (en) * | 1995-11-24 | 1996-01-24 | Smithkline Beecham Spa | Novel compounds |
US7250389B1 (en) | 1998-02-06 | 2007-07-31 | Meiji Seika Kaisha, Ltd. | Antifungal compound and process for producing the same |
US6133447A (en) * | 1998-02-27 | 2000-10-17 | Novartis Crop Protection, Inc. | Process for the preparation of substituted pyridines |
CA2353627C (en) | 1998-11-04 | 2010-10-26 | Keiichi Imamura | Picolinamide derivative and harmful organism control agent comprising said picolinamide derivative as active component |
US6355660B1 (en) | 1999-07-20 | 2002-03-12 | Dow Agrosciences Llc | Fungicidal heterocyclic aromatic amides and their compositions, methods of use and preparation |
US20020177578A1 (en) | 1999-07-20 | 2002-11-28 | Ricks Michael J. | Fungicidal heterocyclic aromatic amides and their compositions, methods of use and preparation |
EP1516875A1 (en) | 1999-07-20 | 2005-03-23 | Dow AgroSciences LLC | Fungicidal heterocyclic aromatic amides and their compositions, methods of use and preparation |
EP1204643B1 (en) * | 1999-08-20 | 2008-06-04 | Dow AgroSciences LLC | Fungicidal heterocyclic aromatic amides and their compositions, methods of use and preparation |
US20050239873A1 (en) | 1999-08-20 | 2005-10-27 | Fred Hutchinson Cancer Research Center | 2 Methoxy antimycin a derivatives and methods of use |
US6642237B1 (en) * | 1999-11-24 | 2003-11-04 | Merck & Co., Inc. | Gamma-hydroxy-2-(fluoroalkylaminocarbonyl)-1-piperazinepentanamides and uses thereof |
KR20040018538A (en) | 2001-07-31 | 2004-03-03 | 다우 아그로사이언시즈 엘엘씨 | Reductive cleavage of the exocyclic ester of UK-2A or its derivatives and products formed therefrom |
AU2002341989A1 (en) | 2001-10-05 | 2003-04-22 | Dow Agrosciences Llc | Process to produce derivatives from uk-2a derivatives |
AR037328A1 (en) | 2001-10-23 | 2004-11-03 | Dow Agrosciences Llc | COMPOSITE OF [7-BENCIL-2,6-DIOXO-1,5-DIOXONAN-3-IL] -4-METOXIPIRIDIN-2-CARBOXAMIDE, COMPOSITION THAT UNDERSTANDS AND METHOD THAT USES IT |
WO2004105490A1 (en) | 2003-05-28 | 2004-12-09 | Basf Aktiengesellschaft | Fungicidal mixtures for controlling rice pathogens |
DE10347090A1 (en) | 2003-10-10 | 2005-05-04 | Bayer Cropscience Ag | Synergistic fungicidal drug combinations |
US20050176767A1 (en) | 2003-10-30 | 2005-08-11 | Laval Chan Chun Kong | Pyridine carboxamide and methods for inhibiting HIV integrase |
EP1751119A1 (en) * | 2004-05-19 | 2007-02-14 | AstraZeneca AB | Novel fused heterocycles and uses thereof |
AU2007238878A1 (en) * | 2006-04-11 | 2007-10-25 | Merck Sharp & Dohme Corp. | Diaryl substituted alkanes |
AU2008303528B2 (en) | 2007-09-26 | 2013-05-23 | Basf Se | Ternary fungicidal compositions comprising boscalid and chlorothalonil |
EP2296467B1 (en) | 2008-05-30 | 2015-11-04 | Dow AgroSciences LLC | Methods to control qoi-resistant fungal pathogens |
CA2747161C (en) * | 2008-12-19 | 2017-07-18 | Abbott Laboratories | (hetero)aryl substituted (benzo[d]thiazol-2-ylcarbamoyl) 1,2,3,4-tetrahydroquinolins and related compounds and uses thereof for treating cancer and excess platelets |
US8470840B2 (en) | 2009-09-01 | 2013-06-25 | Dow Agrosciences, Llc. | Synergistic fungicidal compositions containing a 5-fluoropyrimidine derivative for fungal control in cereals |
PT3178321T (en) | 2009-10-07 | 2019-08-01 | Dow Agrosciences Llc | Synergistic fungicidal mixtures of epoxiconazole for fungal control in cereals |
JP5655080B2 (en) | 2009-10-07 | 2015-01-14 | ダウ アグロサイエンシィズ エルエルシー | Synergistic fungicidal composition containing 5-fluorocytosine for controlling fungi in cereals |
EA022245B1 (en) | 2009-12-08 | 2015-11-30 | Басф Се | Pesticidal mixtures |
JP2014503504A (en) | 2010-11-24 | 2014-02-13 | ステマージ バイオテクノロジー エスエー | Inhibitors of the activity of complex III of the mitochondrial electron transport system and use thereof for treating diseases |
JP6013032B2 (en) | 2011-07-08 | 2016-10-25 | 石原産業株式会社 | Disinfectant composition and method for controlling plant diseases |
RU2014149194A (en) | 2012-05-07 | 2016-06-27 | ДАУ АГРОСАЙЕНСИЗ ЭлЭлСи | MACROCYCLIC PICOLINAMIDES AS FUNGICIDES |
JP6129300B2 (en) | 2012-05-07 | 2017-05-17 | ダウ アグロサイエンシィズ エルエルシー | Macrocyclic picolinamides as fungicides |
WO2013169662A2 (en) | 2012-05-07 | 2013-11-14 | Dow Agrosciences Llc | Macrocyclic picolinamides as fungicides |
ES2666144T3 (en) | 2012-12-28 | 2018-05-03 | Dow Agrosciences Llc | Synergistic fungicidal mixtures for fungal control in cereals |
WO2014105817A1 (en) | 2012-12-31 | 2014-07-03 | Dow Agrosciences Llc | Macrocyclic picolinamides as fungicides |
-
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6521622B1 (en) * | 1999-07-20 | 2003-02-18 | Dow Agrosciences Llc | Fungicidal heterocyclic aromatic amides and their compositions, methods of use and preparation |
Non-Patent Citations (5)
Title |
---|
BARAUH ET AL.: "Synthesis, anticonvulsant activity, and neuropathic pain-attenuating activity of N -benzyl 2-amino-2-(hetero)aromatic acetamides", BIORGANIC AND MEDICINAL CHEMISTRY, vol. 20, 2012, pages 3551 - 3564, XP028423311, DOI: doi:10.1016/j.bmc.2012.04.002 * |
DEMIR ET AL.: "An asymmetric synthesis of both enantiomers of 2,2-trifluoro-1-furan-2-yl- ethylamine and 3,3,3-trifluoroalanine from 2,2,2-trifluoro-1-furan-2-yl-ethanone", TETRAHEDRON : ASYMMETRY, vol. 22, 2001, pages 2309 - 2313, XP004320137, DOI: doi:10.1016/S0957-4166(01)00410-4 * |
KAAS ET AL.: "Preparation of Derivatives of 3-hydroxypicolinic acid from Furfural", ACTA CHIMICA SCANDINAVICA, vol. 19, 1965, pages 1147 - 1152, XP055381380 * |
See also references of EP3166928A4 * |
SHI ET AL.: "Unsaturated beta,beta,-difluroro-alpha-keto esters: Novel and Utility as Precursors of beta,beta-difluoro amino acids", JOURNAL OF ORGANIC CHEMISTRY, vol. 60, 1995, pages 6289 - 6295, XP055383433 * |
Cited By (1)
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