NO327912B1 - Fremgangsmate for fremstilling av fenyleddiksyrederivater - Google Patents

Fremgangsmate for fremstilling av fenyleddiksyrederivater Download PDF

Info

Publication number: NO327912B1
Authority: NO; Norway
Prior art keywords: methyl; phenylacetic acid; ethyl; chloro; compound
Prior art date: 1999-09-27

Application number

NO20021368A

Other languages

English (en)

Norwegian (no)

Other versions

NO20021368D0 (no

NO20021368L (no

Inventor

Gottfried Sedelmeier

Murat Acemoglu

Thomas Allmendinger

John Vincent Calienni

Jacques Cercus

Olivier Loiseleur

David Xu

Original Assignee

Novartis Ag

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-09-27

Filing date

2002-03-19

Publication date

2009-10-19

2002-03-19 Application filed by Novartis Ag filed Critical Novartis Ag

2002-03-19 Publication of NO20021368D0 publication Critical patent/NO20021368D0/no

2002-05-27 Publication of NO20021368L publication Critical patent/NO20021368L/no

2009-10-19 Publication of NO327912B1 publication Critical patent/NO327912B1/no

Links

238000000034 method Methods 0.000 title claims description 33
230000008569 process Effects 0.000 title claims description 8
238000002360 preparation method Methods 0.000 title claims description 7
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 title claims description 5
150000001875 compounds Chemical class 0.000 claims description 63
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
239000011737 fluorine Substances 0.000 claims description 30
229910052731 fluorine Inorganic materials 0.000 claims description 30
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 28
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
150000003839 salts Chemical class 0.000 claims description 23
239000000460 chlorine Substances 0.000 claims description 21
229910052801 chlorine Inorganic materials 0.000 claims description 21
239000001257 hydrogen Substances 0.000 claims description 19
229910052739 hydrogen Inorganic materials 0.000 claims description 19
-1 methoxy, ethoxy Chemical group 0.000 claims description 19
239000002253 acid Substances 0.000 claims description 16
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
150000003951 lactams Chemical class 0.000 claims description 11
ZDDWMWKQAQNCBL-UHFFFAOYSA-N 2-[2-(2,6-dichloroanilino)-5-methylphenyl]acetic acid Chemical class OC(=O)CC1=CC(C)=CC=C1NC1=C(Cl)C=CC=C1Cl ZDDWMWKQAQNCBL-UHFFFAOYSA-N 0.000 claims description 8
125000001309 chloro group Chemical group Cl* 0.000 claims description 8
125000001153 fluoro group Chemical group F* 0.000 claims description 7
MNODWERQWKSALS-UHFFFAOYSA-N 2-chloro-n-(4-ethylphenyl)acetamide Chemical compound CCC1=CC=C(NC(=O)CCl)C=C1 MNODWERQWKSALS-UHFFFAOYSA-N 0.000 claims description 6
CITIOELQTFSEGI-UHFFFAOYSA-N 2-chloro-n-(4-methylphenyl)acetamide Chemical compound CC1=CC=C(NC(=O)CCl)C=C1 CITIOELQTFSEGI-UHFFFAOYSA-N 0.000 claims description 6
150000002148 esters Chemical class 0.000 claims description 6
150000002431 hydrogen Chemical class 0.000 claims description 6
230000007062 hydrolysis Effects 0.000 claims description 6
238000006460 hydrolysis reaction Methods 0.000 claims description 6
230000008707 rearrangement Effects 0.000 claims description 6
WNTCSUFHVADDOL-UHFFFAOYSA-N 2-[2-(2,6-dichloro-4-methylanilino)-5-methylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(Cl)C=C(C)C=C1Cl WNTCSUFHVADDOL-UHFFFAOYSA-N 0.000 claims description 5
KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
OKGJGFZQNSWNSS-UHFFFAOYSA-N 2-[2-(2,4-dichloro-6-methylanilino)-5-ethylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(CC)=CC=C1NC1=C(C)C=C(Cl)C=C1Cl OKGJGFZQNSWNSS-UHFFFAOYSA-N 0.000 claims description 4
FOCAPAVONNWFIB-UHFFFAOYSA-N 2-[2-(2-chloro-6-fluoroanilino)-5-ethylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(CC)=CC=C1NC1=C(F)C=CC=C1Cl FOCAPAVONNWFIB-UHFFFAOYSA-N 0.000 claims description 4
LUWAPCYWGRXGEB-UHFFFAOYSA-N 2-[2-(2-chloro-6-methylanilino)-5-ethylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(CC)=CC=C1NC1=C(C)C=CC=C1Cl LUWAPCYWGRXGEB-UHFFFAOYSA-N 0.000 claims description 4
230000002452 interceptive effect Effects 0.000 claims description 4
238000002955 isolation Methods 0.000 claims description 4
229940002612 prodrug Drugs 0.000 claims description 4
239000000651 prodrug Substances 0.000 claims description 4
239000011734 sodium Chemical class 0.000 claims description 4
KWHODPWZIFFVQM-UHFFFAOYSA-N 2-[2-(2-chloro-4-fluoro-6-methylanilino)-5-methylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(C)C=C(F)C=C1Cl KWHODPWZIFFVQM-UHFFFAOYSA-N 0.000 claims description 3
WSKJPVJRMSBMPJ-UHFFFAOYSA-N 2-[2-(2-chloro-6-methylanilino)-5-methylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(C)C=CC=C1Cl WSKJPVJRMSBMPJ-UHFFFAOYSA-N 0.000 claims description 3
FUHNNQYPOKYIQI-UHFFFAOYSA-N 2-[5-ethyl-2-(2,3,6-trifluoroanilino)phenyl]acetic acid Chemical compound OC(=O)CC1=CC(CC)=CC=C1NC1=C(F)C=CC(F)=C1F FUHNNQYPOKYIQI-UHFFFAOYSA-N 0.000 claims description 3
IZQAIJAGBFXJGP-UHFFFAOYSA-N 2-[5-methyl-2-(2,3,4,6-tetrafluoroanilino)phenyl]acetic acid Chemical class OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=C(F)C(F)=C1F IZQAIJAGBFXJGP-UHFFFAOYSA-N 0.000 claims description 3
230000006181 N-acylation Effects 0.000 claims description 3
230000029936 alkylation Effects 0.000 claims description 3
238000005804 alkylation reaction Methods 0.000 claims description 3
238000003776 cleavage reaction Methods 0.000 claims description 3
230000007017 scission Effects 0.000 claims description 3
229910052708 sodium Inorganic materials 0.000 claims description 3
NZQRBJYQPQLKPB-UHFFFAOYSA-N 2-[2-(2,4-dichloro-6-fluoroanilino)-5-ethylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(CC)=CC=C1NC1=C(F)C=C(Cl)C=C1Cl NZQRBJYQPQLKPB-UHFFFAOYSA-N 0.000 claims description 2
SXFRVOKANDUVRZ-UHFFFAOYSA-N 2-[2-(2,4-dichloro-6-fluoroanilino)-5-methylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=C(Cl)C=C1Cl SXFRVOKANDUVRZ-UHFFFAOYSA-N 0.000 claims description 2
AOPXCXXMJQKVHW-UHFFFAOYSA-N 2-[2-(2,4-dichloro-6-methylanilino)-5-methylphenyl]acetic acid Chemical class OC(=O)CC1=CC(C)=CC=C1NC1=C(C)C=C(Cl)C=C1Cl AOPXCXXMJQKVHW-UHFFFAOYSA-N 0.000 claims description 2
HYMMXWQBWRXAMG-UHFFFAOYSA-N 2-[2-(2,4-difluoro-6-methylanilino)-5-ethylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(CC)=CC=C1NC1=C(C)C=C(F)C=C1F HYMMXWQBWRXAMG-UHFFFAOYSA-N 0.000 claims description 2
GGYRSGWOLQZQFT-UHFFFAOYSA-N 2-[2-(2-chloro-4,6-difluoroanilino)-5-ethylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(CC)=CC=C1NC1=C(F)C=C(F)C=C1Cl GGYRSGWOLQZQFT-UHFFFAOYSA-N 0.000 claims description 2
DIBRALKMONMLNT-UHFFFAOYSA-N 2-[2-(2-chloro-4,6-difluoroanilino)-5-methylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=C(F)C=C1Cl DIBRALKMONMLNT-UHFFFAOYSA-N 0.000 claims description 2
ZQWAHOFWNMJMKC-UHFFFAOYSA-N 2-[2-(2-chloro-4-fluoro-6-methylanilino)-5-ethylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(CC)=CC=C1NC1=C(C)C=C(F)C=C1Cl ZQWAHOFWNMJMKC-UHFFFAOYSA-N 0.000 claims description 2
HWWCFWSHRQUXFB-UHFFFAOYSA-N 2-[2-(4-chloro-2-fluoro-6-methylanilino)-5-ethylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(CC)=CC=C1NC1=C(C)C=C(Cl)C=C1F HWWCFWSHRQUXFB-UHFFFAOYSA-N 0.000 claims description 2
WDEMBAUGAMYMMT-UHFFFAOYSA-N 2-[2-(4-ethoxy-2,3,5,6-tetrafluoroanilino)-5-ethylphenyl]acetic acid Chemical compound FC1=C(F)C(OCC)=C(F)C(F)=C1NC1=CC=C(CC)C=C1CC(O)=O WDEMBAUGAMYMMT-UHFFFAOYSA-N 0.000 claims description 2
ZRIKWKVMCZQPLV-UHFFFAOYSA-N 2-[2-[2,4-dichloro-6-(trifluoromethyl)anilino]-5-methylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(Cl)C=C(Cl)C=C1C(F)(F)F ZRIKWKVMCZQPLV-UHFFFAOYSA-N 0.000 claims description 2
ZUGPVDPUDBNEBJ-UHFFFAOYSA-N 2-[2-[2-fluoro-6-(trifluoromethyl)anilino]-5-methylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1C(F)(F)F ZUGPVDPUDBNEBJ-UHFFFAOYSA-N 0.000 claims description 2
IFXLBMAYBHSJDL-UHFFFAOYSA-N 2-[5-methyl-2-(2,3,5,6-tetrafluoroanilino)phenyl]acetic acid Chemical class OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C(F)=CC(F)=C1F IFXLBMAYBHSJDL-UHFFFAOYSA-N 0.000 claims description 2
230000003301 hydrolyzing effect Effects 0.000 claims description 2
LUNFHOZKXHTOLG-UHFFFAOYSA-N hydroxylumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=C(O)C=C1Cl LUNFHOZKXHTOLG-UHFFFAOYSA-N 0.000 claims description 2
239000003279 phenylacetic acid Substances 0.000 claims description 2
229960003424 phenylacetic acid Drugs 0.000 claims description 2
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical class [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 claims 1
230000009466 transformation Effects 0.000 claims 1
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 141
239000000203 mixture Substances 0.000 description 44
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 30
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 30
238000005481 NMR spectroscopy Methods 0.000 description 29
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
239000011541 reaction mixture Substances 0.000 description 23
239000000243 solution Substances 0.000 description 23
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
239000012074 organic phase Substances 0.000 description 19
239000000047 product Substances 0.000 description 19
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
238000002844 melting Methods 0.000 description 18
230000008018 melting Effects 0.000 description 18
238000003756 stirring Methods 0.000 description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
229910052757 nitrogen Inorganic materials 0.000 description 15
239000000377 silicon dioxide Substances 0.000 description 15
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 13
ZMXDDKWLCZADIW-YYWVXINBSA-N N,N-dimethylformamide-d7 Chemical compound [2H]C(=O)N(C([2H])([2H])[2H])C([2H])([2H])[2H] ZMXDDKWLCZADIW-YYWVXINBSA-N 0.000 description 12
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
239000002904 solvent Substances 0.000 description 12
BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
239000003480 eluent Substances 0.000 description 11
239000012071 phase Substances 0.000 description 11
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
229960004592 isopropanol Drugs 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 9
238000010992 reflux Methods 0.000 description 9
BVNOCBXOCQCOBL-UHFFFAOYSA-N 1-methoxy-4-methylcyclohexa-1,4-diene Chemical compound COC1=CCC(C)=CC1 BVNOCBXOCQCOBL-UHFFFAOYSA-N 0.000 description 8
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 8
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 7
238000003818 flash chromatography Methods 0.000 description 7
229910052740 iodine Inorganic materials 0.000 description 7
239000011630 iodine Substances 0.000 description 7
239000007788 liquid Substances 0.000 description 7
239000003921 oil Substances 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
229910002027 silica gel Inorganic materials 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
URFPRAHGGBYNPW-UHFFFAOYSA-N 1-bromo-4-ethylbenzene Chemical compound CCC1=CC=C(Br)C=C1 URFPRAHGGBYNPW-UHFFFAOYSA-N 0.000 description 6
PDSVDIFOENFADO-UHFFFAOYSA-N 1-ethyl-4-methoxycyclohexa-1,4-diene Chemical compound CCC1=CCC(OC)=CC1 PDSVDIFOENFADO-UHFFFAOYSA-N 0.000 description 6
HRXZRAXKKNUKRF-UHFFFAOYSA-N 4-ethylaniline Chemical compound CCC1=CC=C(N)C=C1 HRXZRAXKKNUKRF-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
238000001914 filtration Methods 0.000 description 6
229910000029 sodium carbonate Inorganic materials 0.000 description 6
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
239000006227 byproduct Substances 0.000 description 5
238000001816 cooling Methods 0.000 description 5
125000004356 hydroxy functional group Chemical group O* 0.000 description 5
239000010410 layer Substances 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
ZBTMRBYMKUEVEU-UHFFFAOYSA-N 1-bromo-4-methylbenzene Chemical compound CC1=CC=C(Br)C=C1 ZBTMRBYMKUEVEU-UHFFFAOYSA-N 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 4
BOXIRPSKMKAVNY-UHFFFAOYSA-N 2-chloro-n-(4-ethylphenyl)-6-methylaniline Chemical compound C1=CC(CC)=CC=C1NC1=C(C)C=CC=C1Cl BOXIRPSKMKAVNY-UHFFFAOYSA-N 0.000 description 4
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
238000005859 coupling reaction Methods 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
238000004519 manufacturing process Methods 0.000 description 4
RZXMPPFPUUCRFN-UHFFFAOYSA-N p-toluidine Chemical group CC1=CC=C(N)C=C1 RZXMPPFPUUCRFN-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
238000007363 ring formation reaction Methods 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 4
239000007787 solid Substances 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
WUYUSIOFCKTMRZ-UHFFFAOYSA-N 1-(2-chloro-6-methylphenyl)-5-ethyl-3h-indol-2-one Chemical compound O=C1CC2=CC(CC)=CC=C2N1C1=C(C)C=CC=C1Cl WUYUSIOFCKTMRZ-UHFFFAOYSA-N 0.000 description 3
GBKUWEPDMMMTIN-UHFFFAOYSA-N 1-(2-chloro-6-methylphenyl)-5-ethyl-5,6-dihydro-4h-indol-2-one Chemical compound O=C1C=C2CC(CC)CC=C2N1C1=C(C)C=CC=C1Cl GBKUWEPDMMMTIN-UHFFFAOYSA-N 0.000 description 3
CSCLMFNQXZSBGQ-UHFFFAOYSA-N 2,3,4,6-tetrafluoro-n-(4-methylphenyl)aniline Chemical compound C1=CC(C)=CC=C1NC1=C(F)C=C(F)C(F)=C1F CSCLMFNQXZSBGQ-UHFFFAOYSA-N 0.000 description 3
VFIWFZMMOBRKHW-UHFFFAOYSA-N 2,4-dichloro-n-(4-ethylphenyl)-6-methylaniline Chemical compound C1=CC(CC)=CC=C1NC1=C(C)C=C(Cl)C=C1Cl VFIWFZMMOBRKHW-UHFFFAOYSA-N 0.000 description 3
TWGIILSJWAIKNP-UHFFFAOYSA-N 2-chloro-4-fluoro-6-methyl-n-(4-methylphenyl)aniline Chemical compound C1=CC(C)=CC=C1NC1=C(C)C=C(F)C=C1Cl TWGIILSJWAIKNP-UHFFFAOYSA-N 0.000 description 3
QBIDTMHZYGYKLF-UHFFFAOYSA-N 2-chloro-6-methyl-n-(4-methylphenyl)aniline Chemical compound C1=CC(C)=CC=C1NC1=C(C)C=CC=C1Cl QBIDTMHZYGYKLF-UHFFFAOYSA-N 0.000 description 3
WFNLHDJJZSJARK-UHFFFAOYSA-N 2-chloro-6-methylaniline Chemical compound CC1=CC=CC(Cl)=C1N WFNLHDJJZSJARK-UHFFFAOYSA-N 0.000 description 3
CTIVURWNBYFUQK-UHFFFAOYSA-N 2-chloro-n-(2-chloro-6-methylphenyl)-n-(4-ethylphenyl)acetamide Chemical compound C1=CC(CC)=CC=C1N(C(=O)CCl)C1=C(C)C=CC=C1Cl CTIVURWNBYFUQK-UHFFFAOYSA-N 0.000 description 3
NBVBURRXINMCJB-UHFFFAOYSA-N 2-chloro-n-(4-methylphenyl)-n-(2,3,4,6-tetrafluorophenyl)acetamide Chemical compound C1=CC(C)=CC=C1N(C(=O)CCl)C1=C(F)C=C(F)C(F)=C1F NBVBURRXINMCJB-UHFFFAOYSA-N 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
230000009102 absorption Effects 0.000 description 3
238000010521 absorption reaction Methods 0.000 description 3
125000005907 alkyl ester group Chemical group 0.000 description 3
239000002585 base Substances 0.000 description 3
238000005660 chlorination reaction Methods 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
230000008878 coupling Effects 0.000 description 3
238000010168 coupling process Methods 0.000 description 3
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239000004289 sodium hydrogen sulphite Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
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239000007864 aqueous solution Substances 0.000 description 2
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238000004587 chromatography analysis Methods 0.000 description 2
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KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
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OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
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YXEOEPYIBGTLML-UHFFFAOYSA-N 2,6-dichloro-4-methylphenol Chemical compound CC1=CC(Cl)=C(O)C(Cl)=C1 YXEOEPYIBGTLML-UHFFFAOYSA-N 0.000 description 1
JDMFXJULNGEPOI-UHFFFAOYSA-N 2,6-dichloroaniline Chemical compound NC1=C(Cl)C=CC=C1Cl JDMFXJULNGEPOI-UHFFFAOYSA-N 0.000 description 1
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NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
CNAXDCSHYHIOGW-UHFFFAOYSA-N 2-bromo-1,3,4-trifluorobenzene Chemical compound FC1=CC=C(F)C(Br)=C1F CNAXDCSHYHIOGW-UHFFFAOYSA-N 0.000 description 1
PLTNCEGFKZZXEI-UHFFFAOYSA-N 2-chloro-4-fluoro-6-methylaniline Chemical compound CC1=CC(F)=CC(Cl)=C1N PLTNCEGFKZZXEI-UHFFFAOYSA-N 0.000 description 1
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AEBQXUBWNRRHKZ-UHFFFAOYSA-N 2-chloro-n-(2,6-dichlorophenyl)-n-(4-methylphenyl)acetamide Chemical compound C1=CC(C)=CC=C1N(C(=O)CCl)C1=C(Cl)C=CC=C1Cl AEBQXUBWNRRHKZ-UHFFFAOYSA-N 0.000 description 1
SVCPNJWCSAOMAH-UHFFFAOYSA-N 2-chloro-n-(2-chloro-6-fluorophenyl)-n-(4-methylphenyl)acetamide Chemical compound C1=CC(C)=CC=C1N(C(=O)CCl)C1=C(F)C=CC=C1Cl SVCPNJWCSAOMAH-UHFFFAOYSA-N 0.000 description 1
XXNJYZYKTNBAPC-UHFFFAOYSA-N 2-chloro-n-(4-ethylphenyl)-n-(2,3,5,6-tetrafluorophenyl)acetamide Chemical compound C1=CC(CC)=CC=C1N(C(=O)CCl)C1=C(F)C(F)=CC(F)=C1F XXNJYZYKTNBAPC-UHFFFAOYSA-N 0.000 description 1
OKSDJGWHKXFVME-UHFFFAOYSA-N 4-ethylcyclohexan-1-one Chemical compound CCC1CCC(=O)CC1 OKSDJGWHKXFVME-UHFFFAOYSA-N 0.000 description 1
229940077398 4-methyl anisole Drugs 0.000 description 1
OHDCGQURSOVSIP-UHFFFAOYSA-N 5-methyl-1-(2,3,4,6-tetrafluorophenyl)-3h-indol-2-one Chemical compound O=C1CC2=CC(C)=CC=C2N1C1=C(F)C=C(F)C(F)=C1F OHDCGQURSOVSIP-UHFFFAOYSA-N 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
238000006027 Birch reduction reaction Methods 0.000 description 1
101150041968 CDC13 gene Proteins 0.000 description 1
238000003547 Friedel-Crafts alkylation reaction Methods 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methyl-N-phenylamine Natural products CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
241001062472 Stokellia anisodon Species 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
239000000538 analytical sample Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
229940111134 coxibs Drugs 0.000 description 1
239000010779 crude oil Substances 0.000 description 1
239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
238000006356 dehydrogenation reaction Methods 0.000 description 1
229940117389 dichlorobenzene Drugs 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical class CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
238000007865 diluting Methods 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
ZANNOFHADGWOLI-UHFFFAOYSA-N ethyl 2-hydroxyacetate Chemical compound CCOC(=O)CO ZANNOFHADGWOLI-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
UAIZDWNSWGTKFZ-UHFFFAOYSA-L ethylaluminum(2+);dichloride Chemical compound CC[Al](Cl)Cl UAIZDWNSWGTKFZ-UHFFFAOYSA-L 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
150000005171 halobenzenes Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
150000002411 histidines Chemical class 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 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-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
RJKWSTDTEPBWBJ-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1C RJKWSTDTEPBWBJ-UHFFFAOYSA-N 0.000 description 1
125000001893 nitrooxy group Chemical group [O-][N+](=O)O* 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
238000005191 phase separation Methods 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000006462 rearrangement reaction Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
239000000523 sample Substances 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
238000007711 solidification Methods 0.000 description 1
230000008023 solidification Effects 0.000 description 1
238000003797 solvolysis reaction Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/43—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C211/44—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring
- C07C211/52—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/43—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C211/54—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to two or three six-membered aromatic rings
- C07C211/56—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to two or three six-membered aromatic rings the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/22—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from lactams, cyclic ketones or cyclic oximes, e.g. by reactions involving Beckmann rearrangement
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/40—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/42—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/12—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
- C07C233/15—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/16—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/18—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides
- C07C235/24—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Rheumatology (AREA)
Pharmacology & Pharmacy (AREA)
Pain & Pain Management (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Indole Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

NO20021368A 1999-09-27 2002-03-19 Fremgangsmate for fremstilling av fenyleddiksyrederivater NO327912B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9922830.6A GB9922830D0 (en)	1999-09-27	1999-09-27	Processes
PCT/EP2000/009346 WO2001023346A2 (en)	1999-09-27	2000-09-25	Process for phenylacetic acid derivatives

Publications (3)

Publication Number	Publication Date
NO20021368D0 NO20021368D0 (no)	2002-03-19
NO20021368L NO20021368L (no)	2002-05-27
NO327912B1 true NO327912B1 (no)	2009-10-19

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Application Number	Title	Priority Date	Filing Date
NO20021368A NO327912B1 (no)	1999-09-27	2002-03-19	Fremgangsmate for fremstilling av fenyleddiksyrederivater

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US (2)	US20080249318A1 (es)
EP (2)	EP2275403A1 (es)
JP (1)	JP2003510303A (es)
KR (1)	KR100745341B1 (es)
CN (1)	CN100412053C (es)
AR (2)	AR031529A1 (es)
AT (1)	ATE447547T1 (es)
AU (1)	AU775416B2 (es)
BR (1)	BR0014314A (es)
CA (1)	CA2379553C (es)
CO (1)	CO5210865A1 (es)
CY (1)	CY1110539T1 (es)
CZ (1)	CZ20021027A3 (es)
DE (1)	DE60043261D1 (es)
DK (1)	DK1216226T3 (es)
EC (2)	ECSP003680A (es)
ES (1)	ES2338209T3 (es)
GB (1)	GB9922830D0 (es)
HK (1)	HK1047739A1 (es)
HU (1)	HUP0202728A3 (es)
IL (2)	IL148330A0 (es)
MY (1)	MY125201A (es)
NO (1)	NO327912B1 (es)
NZ (1)	NZ517461A (es)
PE (1)	PE20010644A1 (es)
PL (1)	PL207777B1 (es)
PT (1)	PT1216226E (es)
RU (1)	RU2273628C2 (es)
SI (1)	SI1216226T1 (es)
SK (1)	SK287241B6 (es)
TR (1)	TR200200745T2 (es)
TW (1)	TWI270540B (es)
WO (1)	WO2001023346A2 (es)
ZA (1)	ZA200202367B (es)

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GB0224198D0 (en) *	2002-10-17	2002-11-27	Novartis Ag	Organic compounds
PE20040844A1 (es)	2002-11-26	2004-12-30	Novartis Ag	Acidos fenilaceticos y derivados como inhibidores de la cox-2
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AR061623A1 (es)	2006-06-26	2008-09-10	Novartis Ag	Derivados de acido fenilacetico
WO2010056741A2 (en)	2008-11-12	2010-05-20	Auspex Pharmaceuticals, Inc.	Phenylacetic acid inhibitors of cyclooxygenase
CN102311355B (zh) *	2011-09-26	2014-02-05	扬州天和药业有限公司	罗本考昔的一种制备方法
CN107721901A (zh) *	2017-11-12	2018-02-23	刘磊	一种2‑[2‑(2,3,5,6‑四氟苯胺基)苯基]乙酸的制备方法
EA202190330A1 (ru)	2018-07-27	2021-06-04	КРКА, д.д., НОВО МЕСТО	Способ получения полиморфной формы робенакоксиба
WO2020027258A1 (ja) *	2018-08-03	2020-02-06	日産化学株式会社	フッ化芳香族第二級アミン化合物の製造方法

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1999
- 1999-09-27 GB GBGB9922830.6A patent/GB9922830D0/en not_active Ceased
2000
- 2000-09-25 AT AT00969292T patent/ATE447547T1/de active
- 2000-09-25 WO PCT/EP2000/009346 patent/WO2001023346A2/en active IP Right Grant
- 2000-09-25 CN CNB008133972A patent/CN100412053C/zh not_active Expired - Fee Related
- 2000-09-25 ES ES00969292T patent/ES2338209T3/es not_active Expired - Lifetime
- 2000-09-25 SK SK414-2002A patent/SK287241B6/sk not_active IP Right Cessation
- 2000-09-25 CA CA2379553A patent/CA2379553C/en not_active Expired - Fee Related
- 2000-09-25 EP EP09171648A patent/EP2275403A1/en not_active Withdrawn
- 2000-09-25 TR TR2002/00745T patent/TR200200745T2/xx unknown
- 2000-09-25 SI SI200031050T patent/SI1216226T1/sl unknown
- 2000-09-25 AR ARP000105014A patent/AR031529A1/es active IP Right Grant
- 2000-09-25 EP EP00969292A patent/EP1216226B1/en not_active Expired - Lifetime
- 2000-09-25 CZ CZ20021027A patent/CZ20021027A3/cs unknown
- 2000-09-25 HU HU0202728A patent/HUP0202728A3/hu unknown
- 2000-09-25 KR KR1020027003901A patent/KR100745341B1/ko not_active IP Right Cessation
- 2000-09-25 DK DK00969292.2T patent/DK1216226T3/da active
- 2000-09-25 NZ NZ517461A patent/NZ517461A/en not_active IP Right Cessation
- 2000-09-25 JP JP2001526501A patent/JP2003510303A/ja active Pending
- 2000-09-25 AU AU79067/00A patent/AU775416B2/en not_active Ceased
- 2000-09-25 PE PE2000001007A patent/PE20010644A1/es not_active Application Discontinuation
- 2000-09-25 BR BR0014314-6A patent/BR0014314A/pt not_active IP Right Cessation
- 2000-09-25 RU RU2002109239/04A patent/RU2273628C2/ru not_active IP Right Cessation
- 2000-09-25 EC EC2000003680A patent/ECSP003680A/es unknown
- 2000-09-25 IL IL14833000A patent/IL148330A0/xx active IP Right Grant
- 2000-09-25 DE DE60043261T patent/DE60043261D1/de not_active Expired - Lifetime
- 2000-09-25 PL PL365994A patent/PL207777B1/pl unknown
- 2000-09-25 PT PT00969292T patent/PT1216226E/pt unknown
- 2000-09-26 MY MYPI20004481 patent/MY125201A/en unknown
- 2000-09-27 TW TWPROCESSFA patent/TWI270540B/zh not_active IP Right Cessation
- 2000-09-27 CO CO00073348A patent/CO5210865A1/es not_active Application Discontinuation
2002
- 2002-02-21 IL IL148330A patent/IL148330A/en not_active IP Right Cessation
- 2002-03-19 NO NO20021368A patent/NO327912B1/no not_active IP Right Cessation
- 2002-03-25 ZA ZA200202367A patent/ZA200202367B/en unknown
- 2002-12-23 HK HK02109296.0A patent/HK1047739A1/xx not_active IP Right Cessation
2003
- 2003-01-10 AR ARP030100070A patent/AR042404A2/es unknown
2007
- 2007-08-16 US US11/893,481 patent/US20080249318A1/en not_active Abandoned
2009
- 2009-01-13 EC EC2009003680A patent/ECSP093680A/es unknown
- 2009-05-07 US US12/436,991 patent/US7906677B2/en not_active Expired - Fee Related
2010
- 2010-02-03 CY CY20101100105T patent/CY1110539T1/el unknown

Also Published As

Publication number	Publication date
TR200200745T2 (tr)	2002-06-21
EP1216226A2 (en)	2002-06-26
IL148330A (en)	2007-02-11
AU775416B2 (en)	2004-07-29
TWI270540B (en)	2007-01-11
PL207777B1 (pl)	2011-01-31
RU2273628C2 (ru)	2006-04-10
ES2338209T3 (es)	2010-05-05
AR031529A1 (es)	2003-09-24
ATE447547T1 (de)	2009-11-15
NO20021368D0 (no)	2002-03-19
PL365994A1 (en)	2005-01-24
SK4142002A3 (en)	2002-08-06
CO5210865A1 (es)	2002-10-30
DK1216226T3 (da)	2010-02-01
CN1377337A (zh)	2002-10-30
KR100745341B1 (ko)	2007-08-02
ECSP003680A (es)	2002-04-23
DE60043261D1 (de)	2009-12-17
GB9922830D0 (en)	1999-11-24
SK287241B6 (sk)	2010-04-07
IL148330A0 (en)	2002-09-12
AR042404A2 (es)	2005-06-22
JP2003510303A (ja)	2003-03-18
HK1047739A1 (en)	2003-03-07
NZ517461A (en)	2003-10-31
PE20010644A1 (es)	2001-06-15
PT1216226E (pt)	2009-12-17
BR0014314A (pt)	2002-11-12
ZA200202367B (en)	2003-02-26
US20080249318A1 (en)	2008-10-09
US20090275758A1 (en)	2009-11-05
EP1216226B1 (en)	2009-11-04
CY1110539T1 (el)	2015-04-29
CZ20021027A3 (cs)	2002-07-17
CA2379553A1 (en)	2001-04-05
WO2001023346A2 (en)	2001-04-05
NO20021368L (no)	2002-05-27
WO2001023346A3 (en)	2002-01-10
KR20020030289A (ko)	2002-04-24
US7906677B2 (en)	2011-03-15
HUP0202728A3 (en)	2003-11-28
CA2379553C (en)	2010-09-21
HUP0202728A2 (hu)	2002-12-28
SI1216226T1 (sl)	2010-03-31
MY125201A (en)	2006-07-31
EP2275403A1 (en)	2011-01-19
AU7906700A (en)	2001-04-30
CN100412053C (zh)	2008-08-20
ECSP093680A (es)	2009-02-27

Legal Events

Date	Code	Title	Description
2013-04-22	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
US7906677B2 (en)	2011-03-15	Process for phenylacetic acid derivatives
US7459580B2 (en)	2008-12-02	Process for trans-4-amino-1-cyclohexanecarboxilic acid derivatives
US7781598B2 (en)	2010-08-24	Process for the preparation of substituted indoles
US7342040B2 (en)	2008-03-11	5-fluorooxindole-3-carboxylic acid ester
US20040039223A1 (en)	2004-02-26	4-Alkoxy cyclohexane-1 amino carboxylic acid esters and method for the production thereof
NO330223B1 (no)	2011-03-07	Fremgangsmate for fremstillingen av perindopril med hoy renhet og intermediater nyttige i syntesen
HU202826B (en)	1991-04-29	Process for producing (2,6-dichloro-phenyl)-amino-phenyl-acetic acid derivatives
RU2362766C2 (ru)	2009-07-27	Способ получения производного бензиламина и производное ацилбензиламина
JP2012532186A (ja)	2012-12-13	４−（アセチルアミノ））−３−［（４−クロロ−フェニル）チオ］−２−メチル−１ｈ−インドール−１−酢酸の製造のための中間体および方法
US4550165A (en)	1985-10-29	Process for producing 1,2,5,6-tetrahydro-4H-pyrrolo-[3,2,1-ij]-quinolin-4-one
IE62321B1 (en)	1995-01-25	New process for the synthesis of the alpha-(1-methylethyl)-3,4-dimethoxybenzeneacetonitrile
US4595755A (en)	1986-06-17	5-halo-1,2,3-(1,2-dihydropyrrolo)-4-quinolones
JP4032593B2 (ja)	2008-01-16	４−アミノテトラヒドロピラン誘導体の製法
EP1568689A1 (en)	2005-08-31	Process for the preparation of the 2-oxoindole derivative, Ropinirole
JP2003055349A (ja)	2003-02-26	キノリン−３−カルボン酸化合物の製造方法