CA1103679A - Traduction non-disponible - Google Patents

Traduction non-disponible

Info

Publication number: CA1103679A
Authority: CA; Canada
Prior art keywords: formula; hydrogen; indolin; reacting; compounds
Prior art date: 1975-08-13
Legal status (The legal status 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 status listed.): Expired

Application number

CA354,687A

Other languages

English (en)

Inventor

Henry W. Moran

William J. Welstead, Jr.

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

AH Robins Co Inc

Original Assignee

AH Robins Co Inc

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.)

1975-08-13

Filing date

1980-06-24

Publication date

1981-06-23

1975-08-13 Priority claimed from US05/604,371 external-priority patent/US4045576A/en

1980-06-24 Application filed by AH Robins Co Inc filed Critical AH Robins Co Inc

1980-06-24 Priority to CA354,687A priority Critical patent/CA1103679A/fr

1981-06-23 Application granted granted Critical

1981-06-23 Publication of CA1103679A publication Critical patent/CA1103679A/fr

Status Expired legal-status Critical Current

Links

PZLOEWPWHWLNOZ-UHFFFAOYSA-N 1-benzoyl-3h-indol-2-one Chemical class O=C1CC2=CC=CC=C2N1C(=O)C1=CC=CC=C1 PZLOEWPWHWLNOZ-UHFFFAOYSA-N 0.000 title abstract description 3
150000001875 compounds Chemical class 0.000 claims abstract description 33
-1 istatins Chemical class 0.000 claims abstract description 23
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 22
239000001257 hydrogen Substances 0.000 claims abstract description 22
125000003545 alkoxy group Chemical group 0.000 claims abstract description 19
125000000217 alkyl group Chemical group 0.000 claims abstract description 12
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 11
239000000460 chlorine Chemical group 0.000 claims abstract description 11
229910052801 chlorine Inorganic materials 0.000 claims abstract description 11
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 10
229910052794 bromium Inorganic materials 0.000 claims abstract description 10
229910052731 fluorine Inorganic materials 0.000 claims abstract description 10
239000011737 fluorine Chemical group 0.000 claims abstract description 10
101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims abstract description 9
150000002431 hydrogen Chemical group 0.000 claims abstract description 9
MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical class NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 claims abstract description 7
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
229910052783 alkali metal Inorganic materials 0.000 claims abstract description 5
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 4
229910052740 iodine Inorganic materials 0.000 claims abstract description 4
239000011630 iodine Chemical group 0.000 claims abstract description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims description 36
238000000034 method Methods 0.000 claims description 20
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 18
230000008569 process Effects 0.000 claims description 13
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 claims description 10
238000006243 chemical reaction Methods 0.000 claims description 10
238000002360 preparation method Methods 0.000 claims description 9
APGQYYFHBPQPTL-UHFFFAOYSA-N 7-benzoyl-1,3-dihydroindol-2-one Chemical class C=1C=CC=2CC(=O)NC=2C=1C(=O)C1=CC=CC=C1 APGQYYFHBPQPTL-UHFFFAOYSA-N 0.000 claims description 8
239000002253 acid Substances 0.000 claims description 8
IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 claims description 8
DZNAJEDQDMDIEL-UHFFFAOYSA-N 5-benzoyl-1,3-dihydroindol-2-one Chemical class C=1C=C2NC(=O)CC2=CC=1C(=O)C1=CC=CC=C1 DZNAJEDQDMDIEL-UHFFFAOYSA-N 0.000 claims description 7
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 claims description 6
OATSQCXMYKYFQO-UHFFFAOYSA-N S-methyl thioacetate Chemical compound CSC(C)=O OATSQCXMYKYFQO-UHFFFAOYSA-N 0.000 claims description 6
QCCDLTOVEPVEJK-UHFFFAOYSA-N phenylacetone Chemical compound CC(=O)CC1=CC=CC=C1 QCCDLTOVEPVEJK-UHFFFAOYSA-N 0.000 claims description 6
239000007868 Raney catalyst Substances 0.000 claims description 5
229910000564 Raney nickel Inorganic materials 0.000 claims description 5
239000000543 intermediate Substances 0.000 claims description 5
NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 claims description 5
239000000126 substance Substances 0.000 claims description 5
238000010531 catalytic reduction reaction Methods 0.000 claims description 4
230000009471 action Effects 0.000 claims description 3
125000001153 fluoro group Chemical group F* 0.000 claims description 3
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims 2
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
JTNQDMOMSQTYFZ-UHFFFAOYSA-N 3-methylsulfanyl-1,3-dihydroindol-2-one Chemical compound C1=CC=C2C(SC)C(=O)NC2=C1 JTNQDMOMSQTYFZ-UHFFFAOYSA-N 0.000 claims 1
125000005530 alkylenedioxy group Chemical group 0.000 claims 1
150000005623 oxindoles Chemical class 0.000 abstract description 3
PRPINYUDVPFIRX-UHFFFAOYSA-N 1-naphthaleneacetic acid Chemical class C1=CC=C2C(CC(=O)O)=CC=CC2=C1 PRPINYUDVPFIRX-UHFFFAOYSA-N 0.000 abstract description 2
229910052784 alkaline earth metal Inorganic materials 0.000 abstract description 2
150000002148 esters Chemical class 0.000 abstract description 2
238000004519 manufacturing process Methods 0.000 abstract description 2
230000000144 pharmacologic effect Effects 0.000 abstract description 2
239000002243 precursor Substances 0.000 abstract description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 44
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
239000000243 solution Substances 0.000 description 34
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
239000000203 mixture Substances 0.000 description 19
238000004458 analytical method Methods 0.000 description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
229960000583 acetic acid Drugs 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 14
235000011054 acetic acid Nutrition 0.000 description 14
239000007787 solid Substances 0.000 description 14
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
239000000706 filtrate Substances 0.000 description 11
239000000047 product Substances 0.000 description 11
239000000463 material Substances 0.000 description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
238000001953 recrystallisation Methods 0.000 description 7
238000003756 stirring Methods 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
AYUWVERWZCNJPS-UHFFFAOYSA-N 2-(2-acetamido-3-benzoylphenyl)acetic acid Chemical compound CC(=O)NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=CC=C1 AYUWVERWZCNJPS-UHFFFAOYSA-N 0.000 description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
229910052736 halogen Inorganic materials 0.000 description 5
150000002367 halogens Chemical class 0.000 description 5
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 5
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
SGQRIUSTBMAYKH-UHFFFAOYSA-N ethyl 2-(2-acetamido-3-benzoylphenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1NC(C)=O SGQRIUSTBMAYKH-UHFFFAOYSA-N 0.000 description 4
TWGHEAQMIPDUKJ-UHFFFAOYSA-N ethyl 2-(2-methyl-3-phenyl-1h-indol-7-yl)acetate Chemical compound CC=1NC=2C(CC(=O)OCC)=CC=CC=2C=1C1=CC=CC=C1 TWGHEAQMIPDUKJ-UHFFFAOYSA-N 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical class O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
229940086542 triethylamine Drugs 0.000 description 4
CKEIDMPVSYWGBQ-UHFFFAOYSA-N 5-benzoyl-3-methyl-1,3-dihydroindol-2-one Chemical compound C1=C2C(C)C(=O)NC2=CC=C1C(=O)C1=CC=CC=C1 CKEIDMPVSYWGBQ-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
239000003637 basic solution Substances 0.000 description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
238000001816 cooling Methods 0.000 description 3
239000006071 cream Substances 0.000 description 3
238000001035 drying Methods 0.000 description 3
238000001914 filtration Methods 0.000 description 3
239000005457 ice water Substances 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
SPIFDSWFDKNERT-UHFFFAOYSA-N nickel;hydrate Chemical compound O.[Ni] SPIFDSWFDKNERT-UHFFFAOYSA-N 0.000 description 3
238000006385 ozonation reaction Methods 0.000 description 3
229960003010 sodium sulfate Drugs 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
239000007858 starting material Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
MHNAXLAGKSOPBH-UHFFFAOYSA-N 1-amino-3h-indol-2-one Chemical compound C1=CC=C2N(N)C(=O)CC2=C1 MHNAXLAGKSOPBH-UHFFFAOYSA-N 0.000 description 2
WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 2
YJMMLTGLBKYWJV-UHFFFAOYSA-N 4-benzoyl-3-methylsulfanyl-1,3-dihydroindol-2-one Chemical compound C=12C(SC)C(=O)NC2=CC=CC=1C(=O)C1=CC=CC=C1 YJMMLTGLBKYWJV-UHFFFAOYSA-N 0.000 description 2
125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 2
VRNAKHQMJZFSTI-UHFFFAOYSA-N 5-(2-fluorobenzoyl)-1,3-dihydroindol-2-one Chemical compound FC1=CC=CC=C1C(=O)C1=CC=C(NC(=O)C2)C2=C1 VRNAKHQMJZFSTI-UHFFFAOYSA-N 0.000 description 2
YHPTWBYCHUXZKU-UHFFFAOYSA-N 5-(4-methoxybenzoyl)-1,3-dihydroindol-2-one Chemical compound C1=CC(OC)=CC=C1C(=O)C1=CC=C(NC(=O)C2)C2=C1 YHPTWBYCHUXZKU-UHFFFAOYSA-N 0.000 description 2
FPCFPKDFYSBNGD-UHFFFAOYSA-N 5-[3-(trifluoromethyl)benzoyl]-1,3-dihydroindol-2-one Chemical compound FC(F)(F)C1=CC=CC(C(=O)C=2C=C3CC(=O)NC3=CC=2)=C1 FPCFPKDFYSBNGD-UHFFFAOYSA-N 0.000 description 2
WWJLCYHYLZZXBE-UHFFFAOYSA-N 5-chloro-1,3-dihydroindol-2-one Chemical compound ClC1=CC=C2NC(=O)CC2=C1 WWJLCYHYLZZXBE-UHFFFAOYSA-N 0.000 description 2
RFCZOOGIQZASOR-UHFFFAOYSA-N 7-(2-fluorobenzoyl)-1,3-dihydroindol-2-one Chemical compound FC1=CC=CC=C1C(=O)C1=CC=CC2=C1NC(=O)C2 RFCZOOGIQZASOR-UHFFFAOYSA-N 0.000 description 2
UVSBYFSXFHZBHB-UHFFFAOYSA-N 7-(4-chlorobenzoyl)-1,3-dihydroindol-2-one Chemical compound C1=CC(Cl)=CC=C1C(=O)C1=CC=CC2=C1NC(=O)C2 UVSBYFSXFHZBHB-UHFFFAOYSA-N 0.000 description 2
GLKCEZPDFADHPT-UHFFFAOYSA-N 7-(4-fluorobenzoyl)-1,3-dihydroindol-2-one Chemical compound C1=CC(F)=CC=C1C(=O)C1=CC=CC2=C1NC(=O)C2 GLKCEZPDFADHPT-UHFFFAOYSA-N 0.000 description 2
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
ACYNEQFBCVVBOJ-PFTUIIQGSA-N ac1l7wrn Chemical compound C12=CC=CC=C2[C@@H]2[C@H]3C4=CC=CC=C4NS(=O)[C@H]3[C@H]1O2 ACYNEQFBCVVBOJ-PFTUIIQGSA-N 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
229960003424 phenylacetic acid Drugs 0.000 description 2
239000003279 phenylacetic acid Substances 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
APHLSUBLNQBFTM-UHFFFAOYSA-N (2-aminophenyl)-(4-chlorophenyl)methanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=C(Cl)C=C1 APHLSUBLNQBFTM-UHFFFAOYSA-N 0.000 description 1
FUADXEJBHCKVBN-UHFFFAOYSA-N (3-aminophenyl)-phenylmethanone Chemical compound NC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 FUADXEJBHCKVBN-UHFFFAOYSA-N 0.000 description 1
FVSGBGVLSLEIMO-UHFFFAOYSA-N (3-benzoylphenyl) acetate Chemical compound CC(=O)OC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 FVSGBGVLSLEIMO-UHFFFAOYSA-N 0.000 description 1
XEUUQQCQFHDEBD-UHFFFAOYSA-N 2-(2-amino-5-benzoylphenyl)acetic acid Chemical compound C1=C(CC(O)=O)C(N)=CC=C1C(=O)C1=CC=CC=C1 XEUUQQCQFHDEBD-UHFFFAOYSA-N 0.000 description 1
IVVGAXUISDFFMZ-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-1-methylquinolin-4-one Chemical compound C=1C(=O)C2=CC=CC=C2N(C)C=1C1=CC=C(O)C=C1 IVVGAXUISDFFMZ-UHFFFAOYSA-N 0.000 description 1
JBUJXUUHQOKXIC-UHFFFAOYSA-N 2-[2-acetamido-3-(2-fluorobenzoyl)phenyl]acetic acid Chemical compound CC(=O)NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=CC=C1F JBUJXUUHQOKXIC-UHFFFAOYSA-N 0.000 description 1
XVGBUTCNTLKREH-UHFFFAOYSA-N 2-[2-amino-3-(2-fluorobenzoyl)phenyl]acetic acid Chemical compound NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=CC=C1F XVGBUTCNTLKREH-UHFFFAOYSA-N 0.000 description 1
GTMSVJVBRIPWOZ-UHFFFAOYSA-N 2-[2-amino-3-(4-chlorobenzoyl)phenyl]acetic acid Chemical compound NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=C(Cl)C=C1 GTMSVJVBRIPWOZ-UHFFFAOYSA-N 0.000 description 1
SPNJTJVYCAYOSI-UHFFFAOYSA-N 2-[2-amino-5-(2-fluorobenzoyl)phenyl]acetic acid Chemical compound C1=C(CC(O)=O)C(N)=CC=C1C(=O)C1=CC=CC=C1F SPNJTJVYCAYOSI-UHFFFAOYSA-N 0.000 description 1
OQSRJXHMJABPIK-UHFFFAOYSA-N 2-[2-amino-5-(4-chlorobenzoyl)phenyl]acetic acid Chemical compound C1=C(CC(O)=O)C(N)=CC=C1C(=O)C1=CC=C(Cl)C=C1 OQSRJXHMJABPIK-UHFFFAOYSA-N 0.000 description 1
RKPPIROBKWRCMB-UHFFFAOYSA-N 2-[2-amino-5-[3-(trifluoromethyl)benzoyl]phenyl]acetic acid Chemical compound C1=C(CC(O)=O)C(N)=CC=C1C(=O)C1=CC=CC(C(F)(F)F)=C1 RKPPIROBKWRCMB-UHFFFAOYSA-N 0.000 description 1
BBZCPUCZKLTAJQ-UHFFFAOYSA-N 3-methyloxindole Chemical compound C1=CC=C2C(C)C(=O)NC2=C1 BBZCPUCZKLTAJQ-UHFFFAOYSA-N 0.000 description 1
NCKMRUDWQDBPAO-UHFFFAOYSA-N 4-benzoyl-1,3-dihydroindol-2-one Chemical compound C=1C=CC=2NC(=O)CC=2C=1C(=O)C1=CC=CC=C1 NCKMRUDWQDBPAO-UHFFFAOYSA-N 0.000 description 1
MUGBOHMVJXRCCN-UHFFFAOYSA-N 5-(4-chlorobenzoyl)-1,3-dihydroindol-2-one Chemical compound C1=CC(Cl)=CC=C1C(=O)C1=CC=C(NC(=O)C2)C2=C1 MUGBOHMVJXRCCN-UHFFFAOYSA-N 0.000 description 1
YMCIVAPEOZDEGH-UHFFFAOYSA-N 5-chloro-2,3-dihydro-1h-indole Chemical compound ClC1=CC=C2NCCC2=C1 YMCIVAPEOZDEGH-UHFFFAOYSA-N 0.000 description 1
SEWGKHCHJHMBKL-UHFFFAOYSA-N 5-methoxy-2,3-dioxo-1h-indole-7-carboxylic acid Chemical compound OC(=O)C1=CC(OC)=CC2=C1NC(=O)C2=O SEWGKHCHJHMBKL-UHFFFAOYSA-N 0.000 description 1
IDZWHMXWYMJEKR-UHFFFAOYSA-N 5-methoxy-2-oxo-1,3-dihydroindole-7-carboxylic acid Chemical compound OC(=O)C1=CC(OC)=CC2=C1NC(=O)C2 IDZWHMXWYMJEKR-UHFFFAOYSA-N 0.000 description 1
VEJGTXTYYIPXPQ-UHFFFAOYSA-N 7-(4-fluorobenzoyl)-3-methylsulfanyl-1,3-dihydroindol-2-one Chemical compound CSC1C(=O)NC2=C1C=CC=C2C(=O)C1=CC=C(F)C=C1 VEJGTXTYYIPXPQ-UHFFFAOYSA-N 0.000 description 1
YYNQPHFJGZQBNT-UHFFFAOYSA-N 7-[3-(trifluoromethyl)benzoyl]-1,3-dihydroindol-2-one Chemical compound FC(F)(F)C1=CC=CC(C(=O)C=2C=3NC(=O)CC=3C=CC=2)=C1 YYNQPHFJGZQBNT-UHFFFAOYSA-N 0.000 description 1
FTKIXYMRJIBPFA-UHFFFAOYSA-N 7-benzoyl-3-methyl-1,3-dihydroindol-2-one Chemical compound CC1C(=O)NC2=C1C=CC=C2C(=O)C1=CC=CC=C1 FTKIXYMRJIBPFA-UHFFFAOYSA-N 0.000 description 1
IVJWUKJUOPAVFI-UHFFFAOYSA-N 7-benzoyl-3-methyl-3-methylsulfanyl-1h-indol-2-one Chemical compound CSC1(C)C(=O)NC2=C1C=CC=C2C(=O)C1=CC=CC=C1 IVJWUKJUOPAVFI-UHFFFAOYSA-N 0.000 description 1
OWFDJANJVJCVAH-UHFFFAOYSA-N 7-benzoyl-3-methylsulfanyl-1,3-dihydroindol-2-one Chemical compound CSC1C(=O)NC2=C1C=CC=C2C(=O)C1=CC=CC=C1 OWFDJANJVJCVAH-UHFFFAOYSA-N 0.000 description 1
GBMZUSIJUCRCSI-UHFFFAOYSA-N 7-benzoyl-5-methoxy-1,3-dihydroindol-2-one Chemical compound C=1C(OC)=CC=2CC(=O)NC=2C=1C(=O)C1=CC=CC=C1 GBMZUSIJUCRCSI-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
241000700159 Rattus Species 0.000 description 1
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
239000003929 acidic solution Substances 0.000 description 1
YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 1
SOYCMDCMZDHQFP-UHFFFAOYSA-N amfenac Chemical compound NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=CC=C1 SOYCMDCMZDHQFP-UHFFFAOYSA-N 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
210000001772 blood platelet Anatomy 0.000 description 1
238000009835 boiling Methods 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
235000011089 carbon dioxide Nutrition 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
239000002026 chloroform extract Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
239000002178 crystalline material Substances 0.000 description 1
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
UUGIKELZUUNRKN-UHFFFAOYSA-N ethyl 2-[2-acetamido-3-(2-fluorobenzoyl)phenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC(C(=O)C=2C(=CC=CC=2)F)=C1NC(C)=O UUGIKELZUUNRKN-UHFFFAOYSA-N 0.000 description 1
KBGFFQIKZUJVSX-UHFFFAOYSA-N ethyl 2-[2-acetamido-3-[3-(trifluoromethyl)benzoyl]phenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC(C(=O)C=2C=C(C=CC=2)C(F)(F)F)=C1NC(C)=O KBGFFQIKZUJVSX-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
125000006332 fluoro benzoyl group Chemical group 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
125000006331 halo benzoyl group Chemical group 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
230000003516 hyperlipidaemic effect Effects 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
238000010899 nucleation Methods 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
229940049953 phenylacetate Drugs 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
239000002002 slurry Substances 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
238000001665 trituration Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1

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Indole Compounds (AREA)

CA354,687A 1975-08-13 1980-06-24 Traduction non-disponible Expired CA1103679A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA354,687A CA1103679A (fr)	1975-08-13	1980-06-24	Traduction non-disponible

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US604,371		1975-08-13
US05/604,371 US4045576A (en)	1975-08-13	1975-08-13	Anti-inflammatory methods using 2-amino-3-(5- and 6-)benzoylphenylacetic acids, esters and metal salts thereof and the compounds
CA248,319A CA1087205A (fr)	1975-08-13	1976-03-19	Acides 2-amino-3-(5-et 6-)benzoylphenylacetiques, leurs esters et sels metalliques
CA354,687A CA1103679A (fr)	1975-08-13	1980-06-24	Traduction non-disponible

Publications (1)

Publication Number	Publication Date
CA1103679A true CA1103679A (fr)	1981-06-23

Family

ID=27164380

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA354,687A Expired CA1103679A (fr)	1975-08-13	1980-06-24	Traduction non-disponible

Country Status (1)

Country	Link
CA (1)	CA1103679A (fr)

1980
- 1980-06-24 CA CA354,687A patent/CA1103679A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1998-06-23	MKEX	Expiry

Publication	Publication Date	Title
US4045576A (en)	1977-08-30	Anti-inflammatory methods using 2-amino-3-(5- and 6-)benzoylphenylacetic acids, esters and metal salts thereof and the compounds
US3963750A (en)	1976-06-15	Thiophene derivatives
CH633515A5 (de)	1982-12-15	Substituierte phenylessigsaeurederivate und verfahren zu ihrer herstellung.
US3975531A (en)	1976-08-17	4-(5- And 7-)benzoylindolin-2-ones and pharmaceutical uses thereof
CA1276938C (fr)	1990-11-27	Derives de l'acide acrylacetique
EP0000128A1 (fr)	1979-01-10	Sulfamoylarylcétones et procédé pour leur préparation ainsi que leur application comme médicament
Ramage et al.	1984	Dioxolanones as synthetic intermediates. Part 2. Synthesis of tetronic acids and pulvinones
US3969402A (en)	1976-07-13	Phenylalkanoic acids
US4003927A (en)	1977-01-18	(1-Oxo-7,8-disubstituted-1,2,3,4-tetrahydro-6-naphthyloxy)- and (3,4-disubstituted-5-oxo-6,7,8,9-tetrahydro-5H-benzocycloheptene-2-yloxy) acetic acids and derivatives
US3308121A (en)	1967-03-07	3-morpholinones, thiones and 5, 6 oxazines
CA1103679A (fr)	1981-06-23	Traduction non-disponible
US4486597A (en)	1984-12-04	Method for the production of nuclear substituted cinnamoylanthranilic acid derivatives
US4007203A (en)	1977-02-08	4-(1-Pyrolidenyl)-2H-1-benzothiopyran-3-carboxanilide
SU576910A3 (ru)	1977-10-15	Способ получени производных замещенной уксусной кислоты или их солей
US3565904A (en)	1971-02-23	1,2,3,4-tetrahydro-1-naphthoic acids
US4153719A (en)	1979-05-08	Aromatic diketones
DE2056173A1 (de)	1971-05-19	3,5 Diphenyl 4 pyrazolessigsaure. ihre m 1 Stellung substituierten Derivate und Verfahren zur Herstellung dieser Verbin düngen
US4080505A (en)	1978-03-21	α-Chlorocarboxylic acids
ROBINSON et al.	1936	The synthesis of substituted 5, 6-benzocinchoninic acids by the Doebner and by the Pfitzinger reactions
US3488363A (en)	1970-01-06	Preparation of alpha-methylphenyl alanines
CH498857A (de)	1970-11-15	Verfahren zur Herstellung von neuen Furazanderivaten
US3981911A (en)	1976-09-21	Process for preparing (1-oxo-2-cyclopentyl-2-methyl-6,7-dichloro-5-indanyloxy)acetic acid
WILKINSON et al.	1961	Total synthesis of tetracyclines. 1 III. 2 synthesis of a tricyclic model system
US4060550A (en)	1977-11-29	Novel n'-acylated phenyl-hydrazine and -hydrazone derivatives
US3576800A (en)	1971-04-27	1-acyl-3-indolyl aliphatic acid derivatives and their method of preparation