FI106459B - Förfarande för framställning av 3-substituerade 2-oxoindolderivat - Google Patents

Förfarande för framställning av 3-substituerade 2-oxoindolderivat Download PDF

Info

Publication number: FI106459B
Authority: FI; Finland
Prior art keywords: mmol; alkyl; eller; oxoindole; phenyl
Prior art date: 1989-04-18

Application number

FI954169A

Other languages

English (en)

Finnish (fi)

Other versions

FI954169A7 (sv

FI954169A0 (sv

Inventor

Carl Joseph Goddard

Gary Richard Schulte

Frederick Jacob Ehrgott

Original Assignee

Pfizer

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.)

1989-04-18

Filing date

1995-09-06

Publication date

2001-02-15

1990-04-17 Priority claimed from FI901915A external-priority patent/FI106378B/sv

1995-09-06 Application filed by Pfizer filed Critical Pfizer

1995-09-06 Priority to FI954169A priority Critical patent/FI106459B/sv

1995-09-06 Publication of FI954169A7 publication Critical patent/FI954169A7/sv

1995-09-06 Publication of FI954169A0 publication Critical patent/FI954169A0/sv

2001-02-15 Application granted granted Critical

2001-02-15 Publication of FI106459B publication Critical patent/FI106459B/sv

Links

238000000034 method Methods 0.000 title claims description 62
-1 3-substituted 2-oxoindole Chemical class 0.000 title claims description 38
238000002360 preparation method Methods 0.000 title claims description 10
230000008569 process Effects 0.000 title claims description 10
238000006243 chemical reaction Methods 0.000 claims description 43
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 40
229910052801 chlorine Inorganic materials 0.000 claims description 34
229910052731 fluorine Inorganic materials 0.000 claims description 31
229910052739 hydrogen Inorganic materials 0.000 claims description 30
229910052794 bromium Inorganic materials 0.000 claims description 27
229910004013 NO 2 Inorganic materials 0.000 claims description 20
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 19
125000000217 alkyl group Chemical group 0.000 claims description 18
229910052760 oxygen Inorganic materials 0.000 claims description 17
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 16
229910052717 sulfur Inorganic materials 0.000 claims description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
239000012298 atmosphere Substances 0.000 claims description 10
239000012442 inert solvent Substances 0.000 claims description 9
229910052740 iodine Inorganic materials 0.000 claims description 9
229910052799 carbon Inorganic materials 0.000 claims description 5
239000000126 substance Substances 0.000 claims description 5
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
101100134925 Gallus gallus COR6 gene Proteins 0.000 claims description 4
QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical class C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 claims description 4
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 description 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
239000003795 chemical substances by application Substances 0.000 claims description 3
125000004043 oxo group Chemical group O=* 0.000 claims description 3
125000001424 substituent group Chemical group 0.000 claims description 3
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims 2
101100295741 Gallus gallus COR4 gene Proteins 0.000 claims 1
239000003153 chemical reaction reagent Substances 0.000 claims 1
239000003086 colorant Substances 0.000 claims 1
229940002612 prodrug Drugs 0.000 claims 1
239000000651 prodrug Substances 0.000 claims 1
150000001875 compounds Chemical class 0.000 description 93
239000007787 solid Substances 0.000 description 83
IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 82
239000000243 solution Substances 0.000 description 71
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 61
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
239000002585 base Substances 0.000 description 53
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 49
238000004458 analytical method Methods 0.000 description 41
239000000460 chlorine Substances 0.000 description 38
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 37
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
238000002451 electron ionisation mass spectrometry Methods 0.000 description 36
239000000203 mixture Substances 0.000 description 36
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
229960000583 acetic acid Drugs 0.000 description 21
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 19
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
229910052943 magnesium sulfate Inorganic materials 0.000 description 18
235000019341 magnesium sulphate Nutrition 0.000 description 18
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 17
102000000589 Interleukin-1 Human genes 0.000 description 17
108010002352 Interleukin-1 Proteins 0.000 description 17
238000001914 filtration Methods 0.000 description 17
210000004027 cell Anatomy 0.000 description 16
239000000543 intermediate Substances 0.000 description 16
238000005481 NMR spectroscopy Methods 0.000 description 15
238000001953 recrystallisation Methods 0.000 description 15
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 13
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
239000000523 sample Substances 0.000 description 13
WGRHBRAKCHCGER-UHFFFAOYSA-N 5-chloro-2-oxo-3h-indole-1-carboxamide Chemical compound ClC1=CC=C2N(C(=O)N)C(=O)CC2=C1 WGRHBRAKCHCGER-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
230000015572 biosynthetic process Effects 0.000 description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
239000002253 acid Substances 0.000 description 11
239000007864 aqueous solution Substances 0.000 description 11
239000000047 product Substances 0.000 description 11
150000003839 salts Chemical class 0.000 description 11
230000001133 acceleration Effects 0.000 description 10
230000002378 acidificating effect Effects 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
239000000725 suspension Substances 0.000 description 10
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
125000000623 heterocyclic group Chemical group 0.000 description 9
239000000463 material Substances 0.000 description 9
229910052757 nitrogen Inorganic materials 0.000 description 9
YIBNHAJFJUQSRA-YNNPMVKQSA-N prostaglandin H2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](O)CCCCC)[C@H]2C\C=C/CCCC(O)=O YIBNHAJFJUQSRA-YNNPMVKQSA-N 0.000 description 9
238000000746 purification Methods 0.000 description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
238000001665 trituration Methods 0.000 description 9
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
239000000538 analytical sample Substances 0.000 description 8
239000002904 solvent Substances 0.000 description 8
238000003756 stirring Methods 0.000 description 8
239000006228 supernatant Substances 0.000 description 8
JWQMRBBWZUKWFJ-UHFFFAOYSA-N 4-chlorothiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=CS1 JWQMRBBWZUKWFJ-UHFFFAOYSA-N 0.000 description 7
208000002193 Pain Diseases 0.000 description 7
230000003187 abdominal effect Effects 0.000 description 7
239000012267 brine Substances 0.000 description 7
239000000284 extract Substances 0.000 description 7
239000003112 inhibitor Substances 0.000 description 7
230000036407 pain Effects 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
241000699670 Mus sp. Species 0.000 description 6
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 6
241000124008 Mammalia Species 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
125000002252 acyl group Chemical group 0.000 description 5
230000000202 analgesic effect Effects 0.000 description 5
125000001246 bromo group Chemical group Br* 0.000 description 5
244000309464 bull Species 0.000 description 5
235000011089 carbon dioxide Nutrition 0.000 description 5
150000003857 carboxamides Chemical class 0.000 description 5
ZMRUPTIKESYGQW-UHFFFAOYSA-N propranolol hydrochloride Chemical compound [H+].[Cl-].C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 ZMRUPTIKESYGQW-UHFFFAOYSA-N 0.000 description 5
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
UYINJAQCJCYCGO-UHFFFAOYSA-N 2-oxo-3h-indole-1-carboxamide Chemical class C1=CC=C2N(C(=O)N)C(=O)CC2=C1 UYINJAQCJCYCGO-UHFFFAOYSA-N 0.000 description 4
RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 4
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
239000005909 Kieselgur Substances 0.000 description 4
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
238000005917 acylation reaction Methods 0.000 description 4
229910052786 argon Inorganic materials 0.000 description 4
239000001569 carbon dioxide Substances 0.000 description 4
229910002092 carbon dioxide Inorganic materials 0.000 description 4
238000001035 drying Methods 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
229910052700 potassium Inorganic materials 0.000 description 4
239000011591 potassium Substances 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 4
SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
238000010998 test method Methods 0.000 description 4
238000012360 testing method Methods 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 3
NEODFWFSTQAKDS-UHFFFAOYSA-N 4-methylsulfanylthiophene-2-carboxylic acid Chemical compound CSC1=CSC(C(O)=O)=C1 NEODFWFSTQAKDS-UHFFFAOYSA-N 0.000 description 3
AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methyl-N-phenylamine Natural products CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
239000012980 RPMI-1640 medium Substances 0.000 description 3
241000700159 Rattus Species 0.000 description 3
230000010933 acylation Effects 0.000 description 3
229910052783 alkali metal Inorganic materials 0.000 description 3
238000003556 assay Methods 0.000 description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
150000001735 carboxylic acids Chemical class 0.000 description 3
239000000679 carrageenan Substances 0.000 description 3
229920001525 carrageenan Polymers 0.000 description 3
235000010418 carrageenan Nutrition 0.000 description 3
229940113118 carrageenan Drugs 0.000 description 3
125000001309 chloro group Chemical group Cl* 0.000 description 3
230000008602 contraction Effects 0.000 description 3
239000012043 crude product Substances 0.000 description 3
239000013078 crystal Substances 0.000 description 3
229940043279 diisopropylamine Drugs 0.000 description 3
201000010099 disease Diseases 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000012530 fluid Substances 0.000 description 3
125000001153 fluoro group Chemical group F* 0.000 description 3
238000007912 intraperitoneal administration Methods 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
239000010410 layer Substances 0.000 description 3
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 3
229910052753 mercury Inorganic materials 0.000 description 3
APNKWEPRZUSZCJ-UHFFFAOYSA-N methyl 5-formylthiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(C=O)S1 APNKWEPRZUSZCJ-UHFFFAOYSA-N 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
229910000029 sodium carbonate Inorganic materials 0.000 description 3
239000012258 stirred mixture Substances 0.000 description 3
208000024891 symptom Diseases 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
125000006701 (C1-C7) alkyl group Chemical group 0.000 description 2
IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 2
PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
238000005160 1H NMR spectroscopy Methods 0.000 description 2
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
IINHDHXDGMTPDH-UHFFFAOYSA-N 3-chloro-2-oxo-3h-indole-1-carboxamide Chemical compound C1=CC=C2N(C(=O)N)C(=O)C(Cl)C2=C1 IINHDHXDGMTPDH-UHFFFAOYSA-N 0.000 description 2
HBXGBMLUGCTBGI-UHFFFAOYSA-N 4-(2-methyl-1,3-thiazol-4-yl)thiophene-2-carboxylic acid Chemical compound S1C(C)=NC(C=2C=C(SC=2)C(O)=O)=C1 HBXGBMLUGCTBGI-UHFFFAOYSA-N 0.000 description 2
IFHFUUUUVWDABB-UHFFFAOYSA-N 4-(dimethylcarbamoyl)thiophene-2-carboxylic acid Chemical compound CN(C)C(=O)C1=CSC(C(O)=O)=C1 IFHFUUUUVWDABB-UHFFFAOYSA-N 0.000 description 2
XYGMOSFVNZUTEK-UHFFFAOYSA-N 4-acetylthiophene-2-carboxylic acid Chemical compound CC(=O)C1=CSC(C(O)=O)=C1 XYGMOSFVNZUTEK-UHFFFAOYSA-N 0.000 description 2
UNUAGYLNEWRKAU-UHFFFAOYSA-N 4-methoxycarbonylthiophene-2-carboxylic acid Chemical compound COC(=O)C1=CSC(C(O)=O)=C1 UNUAGYLNEWRKAU-UHFFFAOYSA-N 0.000 description 2
JGIKSUJIUCEEHP-UHFFFAOYSA-N 4-methylsulfinylthiophene-2-carboxylic acid Chemical compound CS(=O)C1=CSC(C(O)=O)=C1 JGIKSUJIUCEEHP-UHFFFAOYSA-N 0.000 description 2
XYBPFWUNJQTZCM-UHFFFAOYSA-N 5-bromofuran-3-carboxylic acid Chemical compound OC(=O)C1=COC(Br)=C1 XYBPFWUNJQTZCM-UHFFFAOYSA-N 0.000 description 2
VFEAMMGYJFFXKV-UHFFFAOYSA-N 5-formylthiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(C=O)S1 VFEAMMGYJFFXKV-UHFFFAOYSA-N 0.000 description 2
DZWLJMCEXWXWRY-UHFFFAOYSA-N 5-formylthiophene-3-carboxylic acid Chemical compound OC(=O)C1=CSC(C=O)=C1 DZWLJMCEXWXWRY-UHFFFAOYSA-N 0.000 description 2
HYHZGBOWRWIEGW-UHFFFAOYSA-N 5-methoxycarbonylthiophene-2-carboxylic acid Chemical compound COC(=O)C1=CC=C(C(O)=O)S1 HYHZGBOWRWIEGW-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
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WQIRCRDOHVDOGH-UHFFFAOYSA-N methyl 5-(5-methyl-1,2,4-oxadiazol-3-yl)thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1C1=NOC(C)=N1 WQIRCRDOHVDOGH-UHFFFAOYSA-N 0.000 description 1
PPZHIVXKYZAXHI-UHFFFAOYSA-N methyl 5-(5-methyl-1,3,4-oxadiazol-2-yl)thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1C1=NN=C(C)O1 PPZHIVXKYZAXHI-UHFFFAOYSA-N 0.000 description 1
KLGYHLXZILYUOL-UHFFFAOYSA-N methyl 5-cyanothiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(C#N)S1 KLGYHLXZILYUOL-UHFFFAOYSA-N 0.000 description 1
LLPYHVJFILOBIZ-UHFFFAOYSA-N methyl 5-formyl-n-hydroxythiophene-2-carboximidate Chemical compound COC(=NO)C1=CC=C(C=O)S1 LLPYHVJFILOBIZ-UHFFFAOYSA-N 0.000 description 1
GNXNZRYWBFMVHK-UHFFFAOYSA-N methyl 5-formylthiophene-3-carboxylate Chemical compound COC(=O)C1=CSC(C=O)=C1 GNXNZRYWBFMVHK-UHFFFAOYSA-N 0.000 description 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
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NUJYNKAXDKAZGE-UHFFFAOYSA-N n,n-dimethylthiophene-2-sulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=CS1 NUJYNKAXDKAZGE-UHFFFAOYSA-N 0.000 description 1
CTIGHRXLNNYNGU-UHFFFAOYSA-N n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=CS1 CTIGHRXLNNYNGU-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
201000008482 osteoarthritis Diseases 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
150000005623 oxindoles Chemical class 0.000 description 1
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238000007911 parenteral administration Methods 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
125000003884 phenylalkyl group Chemical group 0.000 description 1
239000004033 plastic Substances 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000001226 reprecipitation Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
238000009738 saturating Methods 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000002356 single layer Substances 0.000 description 1
208000013363 skeletal muscle disease Diseases 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
238000010186 staining Methods 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
210000001562 sternum Anatomy 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 1
DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
YCGAZNXXGKTASZ-UHFFFAOYSA-N thiophene-2,5-dicarboxylic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)S1 YCGAZNXXGKTASZ-UHFFFAOYSA-N 0.000 description 1
208000008732 thymoma Diseases 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1

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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

FI954169A 1989-04-18 1995-09-06 Förfarande för framställning av 3-substituerade 2-oxoindolderivat FI106459B (sv)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
FI954169A FI106459B (sv)	1989-04-18	1995-09-06	Förfarande för framställning av 3-substituerade 2-oxoindolderivat

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
US34011389A	1989-04-18	1989-04-18
US34011389		1989-04-18
FI901915		1990-04-17
FI901915A FI106378B (sv)	1989-04-18	1990-04-17	Förfarande för framställning av terapeutiskt användbara 3-substituerade 2-oxoindolderivat
FI954169A FI106459B (sv)	1989-04-18	1995-09-06	Förfarande för framställning av 3-substituerade 2-oxoindolderivat
FI954169		1995-09-06

Publications (3)

Publication Number	Publication Date
FI954169A7 FI954169A7 (sv)	1995-09-06
FI954169A0 FI954169A0 (sv)	1995-09-06
FI106459B true FI106459B (sv)	2001-02-15

Family

ID=27241404

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI954169A FI106459B (sv)	1989-04-18	1995-09-06	Förfarande för framställning av 3-substituerade 2-oxoindolderivat

Country Status (1)

Country	Link
FI (1)	FI106459B (sv)

1995
- 1995-09-06 FI FI954169A patent/FI106459B/sv not_active IP Right Cessation

Also Published As

Publication number	Publication date
FI954169A7 (sv)	1995-09-06
FI954169A0 (sv)	1995-09-06

Publication	Publication Date	Title
FI106378B (sv)	2001-01-31	Förfarande för framställning av terapeutiskt användbara 3-substituerade 2-oxoindolderivat
AU635593B2 (en)	1993-03-25	Azaoxindole derivatives
FI106459B (sv)	2001-02-15	Förfarande för framställning av 3-substituerade 2-oxoindolderivat
US5064851A (en)	1991-11-12	3-(1-substituted-pyrazoyl)-2-oxindole derivatives, compositions and use
US5300655A (en)	1994-04-05	2-carboxy-thiophene derivatives
NO177305B (no)	1995-05-15	Fremgangsmåte for fremstilling av 3-substituerte-2-oksindol-derivater
FI94247B (sv)	1995-04-28	Förfarande för framställning av terapeutiskt användbara 1-heteroaryloxoindol-3-karboxamider

Legal Events

Date	Code	Title	Description
2004-10-31	MA	Patent expired