DK2997014T3 - Fremgangsmåde til fremstilling af 6-trifluormethylpyridin-3-carboxylsyrederivater fra trifluoracetyleddikesyre - Google Patents
Fremgangsmåde til fremstilling af 6-trifluormethylpyridin-3-carboxylsyrederivater fra trifluoracetyleddikesyre Download PDFInfo
- Publication number
- DK2997014T3 DK2997014T3 DK14739475.3T DK14739475T DK2997014T3 DK 2997014 T3 DK2997014 T3 DK 2997014T3 DK 14739475 T DK14739475 T DK 14739475T DK 2997014 T3 DK2997014 T3 DK 2997014T3
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- DK
- Denmark
- Prior art keywords
- alkyl
- group
- compound
- formula
- acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 25
- JNYLMODTPLSLIF-UHFFFAOYSA-N 6-(trifluoromethyl)pyridine-3-carboxylic acid Chemical class OC(=O)C1=CC=C(C(F)(F)F)N=C1 JNYLMODTPLSLIF-UHFFFAOYSA-N 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title description 11
- 150000001875 compounds Chemical class 0.000 claims description 73
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 238000006243 chemical reaction Methods 0.000 claims description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- -1 CH = CH 2 Chemical group 0.000 claims description 10
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 7
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 5
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims description 5
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 4
- 101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 4
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 4
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 238000005580 one pot reaction Methods 0.000 claims description 3
- 235000019260 propionic acid Nutrition 0.000 claims description 3
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 3
- 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 claims description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 claims description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 2
- 239000012346 acetyl chloride Substances 0.000 claims description 2
- 229960005215 dichloroacetic acid Drugs 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims 1
- 125000004957 naphthylene group Chemical group 0.000 claims 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims 1
- ATRQECRSCHYSNP-UHFFFAOYSA-N 2-(trifluoromethyl)pyridine Chemical class FC(F)(F)C1=CC=CC=N1 ATRQECRSCHYSNP-UHFFFAOYSA-N 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- LIQBKSIZAXKCPA-UHFFFAOYSA-N 4,4,4-trifluoro-3-oxobutanoic acid Chemical compound OC(=O)CC(=O)C(F)(F)F LIQBKSIZAXKCPA-UHFFFAOYSA-N 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical class C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 4
- 150000002081 enamines Chemical class 0.000 description 4
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 150000002905 orthoesters Chemical class 0.000 description 4
- 230000020477 pH reduction Effects 0.000 description 4
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- 229910004727 OSO3H Inorganic materials 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 150000002084 enol ethers Chemical class 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 150000002373 hemiacetals Chemical class 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 2
- YKYIFUROKBDHCY-ONEGZZNKSA-N (e)-4-ethoxy-1,1,1-trifluorobut-3-en-2-one Chemical compound CCO\C=C\C(=O)C(F)(F)F YKYIFUROKBDHCY-ONEGZZNKSA-N 0.000 description 2
- FHUDAMLDXFJHJE-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-one Chemical compound CC(=O)C(F)(F)F FHUDAMLDXFJHJE-UHFFFAOYSA-N 0.000 description 2
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical compound CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical class NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000005997 bromomethyl group Chemical group 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical compound CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- RQMWVVBHJMUJNZ-UHFFFAOYSA-N 4-chloropyridin-2-amine Chemical group NC1=CC(Cl)=CC=N1 RQMWVVBHJMUJNZ-UHFFFAOYSA-N 0.000 description 1
- BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 1
- RNPUKIBQXKMPSG-UHFFFAOYSA-N CC(=O)C(F)(F)F.CC(=O)C(F)(F)F Chemical compound CC(=O)C(F)(F)F.CC(=O)C(F)(F)F RNPUKIBQXKMPSG-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- MPZFNWUSPPJWCF-UHFFFAOYSA-N FC(C(=O)C(=O)C(C(F)(F)F)=O)(F)F Chemical class FC(C(=O)C(=O)C(C(F)(F)F)=O)(F)F MPZFNWUSPPJWCF-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- ZKGNPQKYVKXMGJ-UHFFFAOYSA-N N,N-dimethylacetamide Chemical compound CN(C)C(C)=O.CN(C)C(C)=O ZKGNPQKYVKXMGJ-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical group ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- JMRYOSQOYJBDOI-UHFFFAOYSA-N dilithium;di(propan-2-yl)azanide Chemical compound [Li+].CC(C)[N-]C(C)C.CC(C)N([Li])C(C)C JMRYOSQOYJBDOI-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- PJAZMPXLWMQNSS-UHFFFAOYSA-N ethyl 3-amino-4-(2-methoxyethoxy)but-2-enoate Chemical compound CCOC(=O)C=C(N)COCCOC PJAZMPXLWMQNSS-UHFFFAOYSA-N 0.000 description 1
- OCJKUQIPRNZDTK-UHFFFAOYSA-N ethyl 4,4,4-trifluoro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)C(F)(F)F OCJKUQIPRNZDTK-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- VWBWQOUWDOULQN-UHFFFAOYSA-N nmp n-methylpyrrolidone Chemical compound CN1CCCC1=O.CN1CCCC1=O VWBWQOUWDOULQN-UHFFFAOYSA-N 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 239000000085 vanilloid receptor antagonist Substances 0.000 description 1
- 229960000834 vinyl ether Drugs 0.000 description 1
- 239000008096 xylene Substances 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Claims (9)
- FREMGANGSMÅDE TIL FREMSTILLING AF 6-TRIFLUORMETHYLPYRIDIN-3-CARBOXYLSYREDERIVATER FRA TRIFLUORACETYLEDDIKESYRE1. Fremgangsmåde tii fremstilling afen forbindelse med formlen (I);Cl) hvilken fremgangsmåde omfatter et trin (trinSI); trinnet (trinSI) omfatter en reaktion (reakSI); reaktionen (reakSI) er en reaktion af en forbindelse med formlen (il) med en forbindelse med formlen (III) og en forbindelse med formlen (SV); forbindelsen med formlen (II) er vaigt fra gruppen bestående af forbindelsen med formlen (11-1), forbindelsen med formlen (SI-2), forbindelsen med formlen (lia) og blandinger deraf;R1 er valgt fra gruppen bestående af Ci-io-a!kyl, Ca-s-cycioalkyl, C(0)-0-C i-4-alkyl, CH=CH2, benzyl, phenyl og naphthyl; Ci-io-aikylen i R1 er usubstitueret eller substitueret med 1, 2, 3, 4 eller 5 identiske eller forskellige substituenter, der er valgt fra gruppen bestående af halogen, OH, 0-C(0)-Ci-5-alkyl, O-C1-1 o-al kyl, S-Ci-10-alkyi, S(0)-Ci-io-a!kyl, S(02)-Ci-io-alkyl, 0-Ci-6-alkyien-0-Ci-6-alkyl, Cs-s-cycloaikyl og 1,2,4-triazolyl; benzylen, phenylen og naphthylen i R1 uafhængigt af hinanden er usubstitueret eller substitueret med 1,2, 3, 4 eller 5 identiske eller forskellige substituenter, der er valgt fra gruppen bestående af halogen, C-M-alkoxy, NO2 og CN; Y er valgt fra gruppen bestående af C-i-6-alkoxy, O-Ci-e-alkylen-O-Ci-e-alkyl, NH2, NHR4 og N(R4)R5; R4 og R5 er identiske eller forskellige og uafhængigt af hinanden er Ci-e-alkyl eller tilsammen repræsenterer en tetramethylen- eller en pentamethyienkæde; R10 er valgt fra gruppen bestående af C-i-e-alkyl, Cs-io-cycioalkyi og phenyl, hvilken phenyl er usubstitueret eller substitueret med 1 eller 2 identiske eller forskellige substituenter, der uafhængigt af hinanden er valgt fra gruppen bestående af halogen, cyano, nitro, Ci~6~alkyl og phenyl; R20 er valgt fra gruppen bestående af Ci-e-alkyl, 0(C0)CH?,, 0(C0)CF3 og OSO3H,
- 2. Fremgangsmåde ifølge krav 1, hvor reaktionen (reakSI) udføres i "one pot".
- 3. Fremgangsmåde ifølge krav 1 eller 2, hvor R1 er valgt fra gruppen bestående af Ci-s-aikyl, C3-6-cycloalkyj, C(0)-0-Ci^-aikyl, CH^CFfa, benzyl og phenyl; Ci-5-aikylen i R1 er usubstitueret eller substitueret med 1,2, 3, 4 eller 5 identiske af forskellige substituenter, der er valgt fra gruppen bestående af halogen, OH, O-C(O)-CH3, O-Ci-5-alkyl, S~Ci 5-alkyi, S(0)-Ci-5-alkyl, S(02)-Ci-5-alkyi, O-C1.4-alkylen-O-C1.4-alkyl , C3-6-cycloalkyl og 1,2,4-triazolyl; benzylen og phenylen i R1 uafhængigt af hinanden er usubstitueret eller substitueret med 1,2,3,4 eller 5 identiske af forskellige substituenter, der er valgt fra gruppen bestående af halogen, C1-2 alkoxy, NO2 og CN.
- 4. Fremgangsmåde ifølge ét eller flere af kravene 1 til 3, hvor Y er valgt fra gruppen bestående af Ci-e-aikoxy, NHR4 og N(R4)R5; R4 og R5 er identiske eller forskellige og uafhængigt af hinanden Ci-e-alky! eller tilsammen repræsenterer en tetramethylen- eller en pentamethyienkæde.
- 5. Fremgangsmåde ifølge ét eller flere af kravene 1 til 4, hvor R10 er valgt fra gruppen bestående af Ci-e-alkyl, Cs-io-cycloalkyl og phenyl, idet phenylen er usubstitueret eller substitueret med 1 eller 2 identiske eller forskellige substituenter, der uafhængigt af hinanden er valgt fra gruppen bestående af halogen, cyano, nitro og Ci-e-alkyl.
- 6. Fremgangsmåde ifølge ét eller flere af kravene 1 til 5, hvor R20 er valgt fra gruppen bestående af Ci-4-aikyi, 0(C0)CH3, 0(C0)CF3 og OSO3H.
- 7. Fremgangsmåde ifølge ét eller flere af kravene 1 til 6, hvor forbindelsen med formlen (II) er valgt fra gruppen bestående af forbindelsen med formlen (11-1), forbindelsen med formlen (Ii-2) og blandinger deraf.
- 8. Fremgangsmåde ifølge ét eller flere af kravene 1 til 7, hvor reaktionen (reakSI) udføres i et opløsningsmiddel; opløsningsmidlet er et opløsningsmiddel (SolvSI), og opløsningsmidlet (SolvSI) er valgt fra gruppen bestående af ethylacetat, butylacetat, dichlormethan, chloroform, acetonitril, propionitril, DMF, DMA, DMSO, sulfolan, THF, 2-methyl-THF, 3-m ethyl-THF, dloxan, 1,2-dimethoxyethan, toluen, benzen, chlorbenzen, nitrobenzen og blandinger deraf.
- 9. Fremgangsmåde ifølge ét eller flere af kravene 1 til 8, hvor reaktionen (reakSI) udføres i nærværelse af en syre, syren er en forbindelse (AddS1); forbindelsen (AddS1) er valgt fra gruppen bestående af eddikesyre, propionsyre, trifluoreddikesyre, trichloreddikesyre, dichloreddikesyre, svovlsyre, saltsyre, eddikesyreanhydrid, acetylchlorid, toluensulfonsyre, camphorsulfonsyre, methansulfonsyre og blandinger deraf.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361856262P | 2013-07-19 | 2013-07-19 | |
| EP13177234 | 2013-07-19 | ||
| EP13195611 | 2013-12-04 | ||
| EP13198150 | 2013-12-18 | ||
| PCT/EP2014/065366 WO2015007837A1 (en) | 2013-07-19 | 2014-07-17 | Method for preparation of 6-trifluoromethylpyridine-3-carboxylic acid derivatives from trifluoroacetylacetic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2997014T3 true DK2997014T3 (da) | 2017-01-09 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK14739475.3T DK2997014T3 (da) | 2013-07-19 | 2014-07-17 | Fremgangsmåde til fremstilling af 6-trifluormethylpyridin-3-carboxylsyrederivater fra trifluoracetyleddikesyre |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US9522885B1 (da) |
| EP (1) | EP2997014B1 (da) |
| JP (1) | JP5965084B1 (da) |
| CN (1) | CN105492427B (da) |
| DK (1) | DK2997014T3 (da) |
| ES (1) | ES2598105T3 (da) |
| HU (1) | HUE032478T2 (da) |
| PL (1) | PL2997014T3 (da) |
| WO (1) | WO2015007837A1 (da) |
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| RU2737893C2 (ru) * | 2015-08-11 | 2020-12-04 | Айсью Медсинз Б.В. | Пэгилированная липидная наночастица с биоактивным липофильным соединением |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6673938B1 (en) | 1998-12-23 | 2004-01-06 | Syngenta Participations Ag | Substituted pyridine herbicides |
| AR023071A1 (es) | 1998-12-23 | 2002-09-04 | Syngenta Participations Ag | Compuestos de piridincetona, compuestos intermediarios, composicion herbicida e inhibidora del crecimiento de plantas, metodo para controlar la vegetacion indeseada, metodo para inhibir el crecimiento de las plantas, y uso de la composicion para controlar el crecimiento indeseado de plantas. |
| WO2004078272A2 (en) * | 2003-02-28 | 2004-09-16 | Nautilus, Inc. | Dual deck exercise device |
| ES2318275T3 (es) * | 2003-03-07 | 2009-05-01 | Syngenta Participations Ag | Procedimiento para la produccion de esteres del acido niocotinico sustituidos. |
| EP1824828A2 (en) * | 2004-12-03 | 2007-08-29 | Peakdale Molecular Limited | Pyridine based compounds useful as intermediates for pharmaceutical or agricultural end-products |
| CA2658925C (en) | 2006-07-27 | 2015-07-14 | Amorepacific Corporation | Novel sulfonylamino acrylamide derivatives, isomer thereof,or pharmaceutically acceptable salts thereof as vanilloid receptor antagonist; and pharmaceutical compositions containing the same |
| US20140113898A1 (en) | 2010-11-08 | 2014-04-24 | Zalicus Pharmaceuticals Ltd. | Bisarylsulfone and dialkylarylsulfone compounds as calcium channel blockers |
-
2014
- 2014-07-17 DK DK14739475.3T patent/DK2997014T3/da active
- 2014-07-17 HU HUE14739475A patent/HUE032478T2/en unknown
- 2014-07-17 EP EP14739475.3A patent/EP2997014B1/en not_active Not-in-force
- 2014-07-17 CN CN201480039992.7A patent/CN105492427B/zh not_active Expired - Fee Related
- 2014-07-17 WO PCT/EP2014/065366 patent/WO2015007837A1/en not_active Ceased
- 2014-07-17 ES ES14739475.3T patent/ES2598105T3/es active Active
- 2014-07-17 US US14/898,791 patent/US9522885B1/en not_active Expired - Fee Related
- 2014-07-17 PL PL14739475T patent/PL2997014T3/pl unknown
- 2014-07-17 JP JP2015563103A patent/JP5965084B1/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20160368876A1 (en) | 2016-12-22 |
| HK1218295A1 (zh) | 2017-02-10 |
| ES2598105T3 (es) | 2017-01-25 |
| EP2997014A1 (en) | 2016-03-23 |
| JP5965084B1 (ja) | 2016-08-03 |
| US9522885B1 (en) | 2016-12-20 |
| PL2997014T3 (pl) | 2017-04-28 |
| HUE032478T2 (en) | 2017-09-28 |
| EP2997014B1 (en) | 2016-09-21 |
| CN105492427B (zh) | 2016-12-14 |
| JP2016525067A (ja) | 2016-08-22 |
| CN105492427A (zh) | 2016-04-13 |
| WO2015007837A1 (en) | 2015-01-22 |
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