ZA200103533B - Process for preparing 1,5-diaryl-3-substituted pyrazoles. - Google Patents

Process for preparing 1,5-diaryl-3-substituted pyrazoles. Download PDF

Info

Publication number: ZA200103533B
Authority: ZA; South Africa
Prior art keywords: formula; compound; reacting; group; trifluoromethyl
Prior art date: 1999-08-03

Application number

ZA200103533A

Other languages

English (en)

Inventor

Ahmed F Abdel-Magid

Bruce D Harris

Cynthia A Maryanoff

Original Assignee

Ortho Mcneil Pharm 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.)

1999-08-03

Filing date

2001-05-02

Publication date

2002-05-02

2001-05-02 Application filed by Ortho Mcneil Pharm Inc filed Critical Ortho Mcneil Pharm Inc

2002-05-02 Publication of ZA200103533B publication Critical patent/ZA200103533B/en

Links

238000004519 manufacturing process Methods 0.000 title claims description 11
150000003217 pyrazoles Chemical class 0.000 title description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 69
150000001875 compounds Chemical class 0.000 claims description 68
238000006243 chemical reaction Methods 0.000 claims description 31
150000002148 esters Chemical class 0.000 claims description 26
238000000034 method Methods 0.000 claims description 23
-1 amino, acetamido, phenyl Chemical group 0.000 claims description 22
125000003545 alkoxy group Chemical group 0.000 claims description 20
125000000217 alkyl group Chemical group 0.000 claims description 18
125000001624 naphthyl group Chemical group 0.000 claims description 18
239000011541 reaction mixture Substances 0.000 claims description 18
RGZRSLKIOCHTSI-UHFFFAOYSA-N hydron;n-methylhydroxylamine;chloride Chemical compound Cl.CNO RGZRSLKIOCHTSI-UHFFFAOYSA-N 0.000 claims description 17
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
150000004703 alkoxides Chemical class 0.000 claims description 13
FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims description 11
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 11
229940014800 succinic anhydride Drugs 0.000 claims description 11
239000002253 acid Substances 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 9
125000005843 halogen group Chemical group 0.000 claims description 9
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
125000004414 alkyl thio group Chemical group 0.000 claims description 8
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 5
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
125000004356 hydroxy functional group Chemical group O* 0.000 claims 7
YKYIFUROKBDHCY-ONEGZZNKSA-N (e)-4-ethoxy-1,1,1-trifluorobut-3-en-2-one Chemical group CCO\C=C\C(=O)C(F)(F)F YKYIFUROKBDHCY-ONEGZZNKSA-N 0.000 claims 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
239000000203 mixture Substances 0.000 description 32
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 25
239000000243 solution Substances 0.000 description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
238000003756 stirring Methods 0.000 description 22
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
239000002585 base Substances 0.000 description 20
239000000047 product Substances 0.000 description 19
239000007787 solid Substances 0.000 description 18
XYKWNRUXCOIMFZ-UHFFFAOYSA-N tepoxalin Chemical compound C1=CC(OC)=CC=C1N1C(C=2C=CC(Cl)=CC=2)=CC(CCC(=O)N(C)O)=N1 XYKWNRUXCOIMFZ-UHFFFAOYSA-N 0.000 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
238000001914 filtration Methods 0.000 description 15
239000005457 ice water Substances 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
238000010992 reflux Methods 0.000 description 15
229950009638 tepoxalin Drugs 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
239000002904 solvent Substances 0.000 description 11
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 9
235000019439 ethyl acetate Nutrition 0.000 description 9
229910052786 argon Inorganic materials 0.000 description 7
238000001816 cooling Methods 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
238000010791 quenching Methods 0.000 description 7
238000000526 short-path distillation Methods 0.000 description 7
238000004809 thin layer chromatography Methods 0.000 description 7
230000001476 alcoholic effect Effects 0.000 description 6
239000012153 distilled water Substances 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
238000005292 vacuum distillation Methods 0.000 description 6
238000001035 drying Methods 0.000 description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
238000003760 magnetic stirring Methods 0.000 description 5
CPQCSJYYDADLCZ-UHFFFAOYSA-N n-methylhydroxylamine Chemical compound CNO CPQCSJYYDADLCZ-UHFFFAOYSA-N 0.000 description 5
BUZYGTVTZYSBCU-UHFFFAOYSA-N 1-(4-chlorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Cl)C=C1 BUZYGTVTZYSBCU-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
239000012362 glacial acetic acid Substances 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
238000010899 nucleation Methods 0.000 description 4
239000002002 slurry Substances 0.000 description 4
239000012265 solid product Substances 0.000 description 4
239000000725 suspension Substances 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
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
125000003118 aryl group Chemical group 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
238000004821 distillation Methods 0.000 description 3
229940093499 ethyl acetate Drugs 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 3
LFQULJPVXNYWAG-UHFFFAOYSA-N sodium;phenylmethanolate Chemical compound [Na]OCC1=CC=CC=C1 LFQULJPVXNYWAG-UHFFFAOYSA-N 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
JWWITSKUTWOSQS-UHFFFAOYSA-N 3-[5-(4-chlorophenyl)-1-(4-methoxyphenyl)pyrazol-3-yl]propanoic acid Chemical compound C1=CC(OC)=CC=C1N1C(C=2C=CC(Cl)=CC=2)=CC(CCC(O)=O)=N1 JWWITSKUTWOSQS-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
239000011521 glass Substances 0.000 description 2
150000003840 hydrochlorides Chemical class 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
XDBOBNVQEBSKFO-UHFFFAOYSA-N magnesium;di(propan-2-yl)azanide Chemical compound CC(C)N(C(C)C)[Mg]N(C(C)C)C(C)C XDBOBNVQEBSKFO-UHFFFAOYSA-N 0.000 description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
239000000843 powder Substances 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
WBQTXTBONIWRGK-UHFFFAOYSA-N sodium;propan-2-olate Chemical compound [Na+].CC(C)[O-] WBQTXTBONIWRGK-UHFFFAOYSA-N 0.000 description 2
239000007858 starting material Substances 0.000 description 2
FQHCPFMTXFJZJS-UHFFFAOYSA-N (4-methoxyphenyl)hydrazine;hydrochloride Chemical compound Cl.COC1=CC=C(NN)C=C1 FQHCPFMTXFJZJS-UHFFFAOYSA-N 0.000 description 1
125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
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
125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000006149 2-ethylbutyl sulfonyl group Chemical group 0.000 description 1
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
SRLOOKOZKNSJDW-UHFFFAOYSA-N 3-[5-(4-chlorophenyl)-1-(4-methoxyphenyl)pyrazol-3-yl]propan-1-ol Chemical compound C1=CC(OC)=CC=C1N1C(C=2C=CC(Cl)=CC=2)=CC(CCCO)=N1 SRLOOKOZKNSJDW-UHFFFAOYSA-N 0.000 description 1
125000005917 3-methylpentyl group Chemical group 0.000 description 1
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
CYAYCOCJAVHQSD-UHFFFAOYSA-N 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxylic acid Chemical compound CC=1C(C(O)=O)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 CYAYCOCJAVHQSD-UHFFFAOYSA-N 0.000 description 1
KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Natural products CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 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
239000003810 Jones reagent Substances 0.000 description 1
102000003820 Lipoxygenases Human genes 0.000 description 1
108090000128 Lipoxygenases Proteins 0.000 description 1
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
150000008062 acetophenones Chemical class 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
238000007605 air drying Methods 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
229940114079 arachidonic acid Drugs 0.000 description 1
235000021342 arachidonic acid Nutrition 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
229940045348 brown mixture Drugs 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
CTVFCMYPYJBKEY-UHFFFAOYSA-N ethyl 3-[5-(4-chlorophenyl)-1-(4-methoxyphenyl)pyrazol-3-yl]propanoate Chemical compound C=1C=C(OC)C=CC=1N1N=C(CCC(=O)OCC)C=C1C1=CC=C(Cl)C=C1 CTVFCMYPYJBKEY-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
125000006125 ethylsulfonyl group Chemical group 0.000 description 1
239000012467 final product Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000000463 material Substances 0.000 description 1
NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
230000037361 pathway Effects 0.000 description 1
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
JOVOSQBPPZZESK-UHFFFAOYSA-N phenylhydrazine hydrochloride Chemical compound Cl.NNC1=CC=CC=C1 JOVOSQBPPZZESK-UHFFFAOYSA-N 0.000 description 1
229940038531 phenylhydrazine hydrochloride Drugs 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
OGHBATFHNDZKSO-UHFFFAOYSA-N propan-2-olate Chemical compound CC(C)[O-] OGHBATFHNDZKSO-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
125000003226 pyrazolyl group Chemical group 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
238000011084 recovery Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- 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]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/083—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid anhydrides
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
- C07C59/88—Unsaturated compounds containing keto groups containing halogen

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ZA200103533A 1999-08-03 2001-05-02 Process for preparing 1,5-diaryl-3-substituted pyrazoles. ZA200103533B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US14699799P	1999-08-03	1999-08-03

Publications (1)

Publication Number	Publication Date
ZA200103533B true ZA200103533B (en)	2002-05-02

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Application Number	Title	Priority Date	Filing Date
ZA200103533A ZA200103533B (en)	1999-08-03	2001-05-02	Process for preparing 1,5-diaryl-3-substituted pyrazoles.

Country Status (26)

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US (4)	US6384233B1 (de)
EP (2)	EP1413575B1 (de)
JP (2)	JP4886951B2 (de)
KR (1)	KR100646883B1 (de)
CN (1)	CN1219771C (de)
AR (1)	AR032589A1 (de)
AT (2)	ATE342254T1 (de)
AU (2)	AU779353B2 (de)
BR (1)	BR0006978B1 (de)
CA (2)	CA2636755C (de)
CZ (2)	CZ299710B6 (de)
DE (2)	DE60015496T2 (de)
DK (1)	DK1413575T3 (de)
ES (2)	ES2274171T3 (de)
HK (1)	HK1040081B (de)
HU (1)	HU228678B1 (de)
IL (2)	IL142341A0 (de)
MY (1)	MY122496A (de)
NO (1)	NO318467B1 (de)
NZ (1)	NZ510890A (de)
PL (1)	PL201799B1 (de)
PT (2)	PT1413575E (de)
RU (1)	RU2243967C2 (de)
TW (1)	TWI234562B (de)
WO (1)	WO2001009102A2 (de)
ZA (1)	ZA200103533B (de)

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EP1413575B1 (de) *	1999-08-03	2006-10-11	Ortho-McNeil Pharmaceutical, Inc.	Verfahren zur Herstellung von Derivaten von ¬(1,5-Diaryl)pyrazol-3-yl\|propansäure
WO2004089303A2 (en) *	2003-04-03	2004-10-21	Merck & Co., Inc.	Di-aryl substituted pyrazole modulators of metabotropic glutamate receptor-5
WO2005019523A2 (en) *	2003-08-19	2005-03-03	Day-Glo Color Corp.	Polymeric colorants and method of coloring thermoplastic resins
EP2805957A1 (de)	2013-05-23	2014-11-26	hameln rds gmbh	Kristalline Formen von Trinatrium-Zink-Diethylen-triaminpentaessigsäure
CN111018785B (zh) *	2019-12-26	2022-02-11	武汉科技大学	一种1-（4-氯苯基）-3-吡唑醇的合成方法及应用

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US4826868A (en) *	1986-05-29	1989-05-02	Ortho Pharmaceutical Corporation	1,5-Diaryl-3-substituted pyrazoles pharmaceutical compositions and use
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US5078780A (en)	1986-10-22	1992-01-07	Ciba-Geigy Corporation	1,5-diphenylpyrazole-3-carboxylic acid derivatives for the protection of cultivated plants
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JPH0699382B2 (ja) *	1987-06-17	1994-12-07	富士写真フイルム株式会社	Ｎ−メチル−α−ジアルキルアミノアセトヒドロキサム酸誘導体
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US5387602A (en)	1993-08-30	1995-02-07	Ortho Pharmaceutical Corporation	1.5-diphenyl-3-(N-hydroxycarbamoyloxyalkyl)pyrazoles
US5412151A (en) *	1993-10-22	1995-05-02	Eastman Chemical Company	Thermosetting coating compositions
JPH0944014A (ja) *	1995-08-03	1997-02-14	Canon Inc	加熱用フィルム、加熱加圧部材、加熱装置及び画像形成装置
US5843958A (en) *	1996-11-27	1998-12-01	Ortho Pharmaceutical Corporation	Arylpyrazoles as leukotriene inhibitors
EP1413575B1 (de) *	1999-08-03	2006-10-11	Ortho-McNeil Pharmaceutical, Inc.	Verfahren zur Herstellung von Derivaten von ¬(1,5-Diaryl)pyrazol-3-yl\|propansäure

2000
- 2000-08-01 EP EP03078588A patent/EP1413575B1/de not_active Expired - Lifetime
- 2000-08-01 HU HU0103778A patent/HU228678B1/hu unknown
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- 2000-08-01 CZ CZ20011202A patent/CZ299710B6/cs not_active IP Right Cessation
- 2000-08-01 PT PT03078588T patent/PT1413575E/pt unknown
- 2000-08-01 ES ES03078588T patent/ES2274171T3/es not_active Expired - Lifetime
- 2000-08-01 EP EP00955303A patent/EP1144382B1/de not_active Expired - Lifetime
- 2000-08-01 WO PCT/US2000/020917 patent/WO2001009102A2/en active Application Filing
- 2000-08-01 CA CA2636755A patent/CA2636755C/en not_active Expired - Lifetime
- 2000-08-01 AT AT03078588T patent/ATE342254T1/de active
- 2000-08-01 PT PT00955303T patent/PT1144382E/pt unknown
- 2000-08-01 DE DE60015496T patent/DE60015496T2/de not_active Expired - Lifetime
- 2000-08-01 CA CA002346142A patent/CA2346142C/en not_active Expired - Lifetime
- 2000-08-01 CN CNB008021058A patent/CN1219771C/zh not_active Expired - Lifetime
- 2000-08-01 KR KR1020017004245A patent/KR100646883B1/ko active IP Right Grant
- 2000-08-01 ES ES00955303T patent/ES2232482T3/es not_active Expired - Lifetime
- 2000-08-01 AT AT00955303T patent/ATE281437T1/de active
- 2000-08-01 AU AU67526/00A patent/AU779353B2/en not_active Expired
- 2000-08-01 BR BRPI0006978-7A patent/BR0006978B1/pt not_active IP Right Cessation
- 2000-08-01 DE DE60031315T patent/DE60031315T2/de not_active Expired - Lifetime
- 2000-08-01 PL PL347025A patent/PL201799B1/pl unknown
- 2000-08-01 CZ CZ20060485A patent/CZ299711B6/cs not_active IP Right Cessation
- 2000-08-01 NZ NZ510890A patent/NZ510890A/en not_active IP Right Cessation
- 2000-08-01 DK DK03078588T patent/DK1413575T3/da active
- 2000-08-01 RU RU2001109261/04A patent/RU2243967C2/ru active
- 2000-08-02 MY MYPI20003528A patent/MY122496A/en unknown
- 2000-08-02 AR ARP000103984A patent/AR032589A1/es active IP Right Grant
- 2000-09-25 TW TW089115548A patent/TWI234562B/zh not_active IP Right Cessation
2001
- 2001-04-02 NO NO20011652A patent/NO318467B1/no not_active IP Right Cessation
- 2001-05-02 ZA ZA200103533A patent/ZA200103533B/en unknown
- 2001-09-28 US US09/966,116 patent/US6384233B1/en not_active Expired - Lifetime
2002
- 2002-03-01 US US10/086,583 patent/US6613914B2/en not_active Expired - Lifetime
- 2002-03-05 HK HK02101683.8A patent/HK1040081B/zh not_active IP Right Cessation
2003
- 2003-06-12 US US10/460,601 patent/US6953860B2/en not_active Expired - Lifetime
2005
- 2005-04-20 AU AU2005201660A patent/AU2005201660A1/en not_active Withdrawn
- 2005-08-30 US US11/215,329 patent/US7247745B2/en not_active Expired - Lifetime
- 2005-11-01 IL IL171712A patent/IL171712A/en active IP Right Grant
2011
- 2011-10-24 JP JP2011233200A patent/JP2012051929A/ja active Pending

Also Published As

Publication number	Publication date
NO20011652L (no)	2001-05-23
JP2003506359A (ja)	2003-02-18
HUP0103778A3 (en)	2002-07-29
CZ20011202A3 (cs)	2001-09-12
AR032589A1 (es)	2003-11-19
CN1219771C (zh)	2005-09-21
DK1413575T3 (da)	2006-12-27
CA2636755C (en)	2010-10-19
CZ299711B6 (cs)	2008-10-29
ES2232482T3 (es)	2005-06-01
BR0006978B1 (pt)	2010-11-30
EP1144382A2 (de)	2001-10-17
EP1413575A2 (de)	2004-04-28
NZ510890A (en)	2003-09-26
WO2001009102A2 (en)	2001-02-08
US20020128487A1 (en)	2002-09-12
US6384233B1 (en)	2002-05-07
EP1413575A3 (de)	2004-10-06
DE60031315D1 (de)	2006-11-23
EP1413575B1 (de)	2006-10-11
PT1144382E (pt)	2005-02-28
EP1144382A3 (de)	2002-09-11
AU779353B2 (en)	2005-01-20
IL171712A (en)	2010-04-29
RU2243967C2 (ru)	2005-01-10
US20040230060A1 (en)	2004-11-18
HUP0103778A2 (hu)	2002-05-29
AU2005201660A1 (en)	2005-05-12
MY122496A (en)	2006-04-29
KR20010075571A (ko)	2001-08-09
PT1413575E (pt)	2006-12-29
US20020032336A1 (en)	2002-03-14
HK1040081B (zh)	2005-05-13
CA2346142A1 (en)	2001-02-08
DE60015496T2 (de)	2005-10-27
JP4886951B2 (ja)	2012-02-29
AU6752600A (en)	2001-02-19
HK1040081A1 (en)	2002-05-24
JP2012051929A (ja)	2012-03-15
DE60015496D1 (de)	2004-12-09
US20060004208A1 (en)	2006-01-05
CN1337951A (zh)	2002-02-27
EP1413575A9 (de)	2005-06-29
KR100646883B1 (ko)	2006-11-17
TWI234562B (en)	2005-06-21
CA2636755A1 (en)	2001-02-08
CA2346142C (en)	2008-10-14
IL142341A0 (en)	2002-03-10
BR0006978A (pt)	2001-06-19
CZ299710B6 (cs)	2008-10-29
ES2274171T3 (es)	2007-05-16
ATE342254T1 (de)	2006-11-15
US6613914B2 (en)	2003-09-02
US6953860B2 (en)	2005-10-11
PL347025A1 (en)	2002-03-11
US7247745B2 (en)	2007-07-24
ATE281437T1 (de)	2004-11-15
DE60031315T2 (de)	2007-04-26
PL201799B1 (pl)	2009-05-29
NO20011652D0 (no)	2001-04-02
NO318467B1 (no)	2005-03-21
EP1144382B1 (de)	2004-11-03
HU228678B1 (en)	2013-05-28
WO2001009102A3 (en)	2001-08-16

Publication	Publication Date	Title
ZA200103533B (en)	2002-05-02	Process for preparing 1,5-diaryl-3-substituted pyrazoles.
KR100720220B1 (ko)	2007-05-21	치환 아닐린 화합물의 제조방법
JP2000212166A (ja)	2000-08-02	１，３―ジアルキルピラゾ―ル―４―カルボン酸エステルの製造法
MXPA01003441A (en)	2002-06-05	Process for preparing 1,5-diaryl-3-substituted pyrazoles
JPH09100278A (ja)	1997-04-15	インドール誘導体の製造法
JP3864763B2 (ja)	2007-01-10	３−ハロ−２−ヒドラゾノ−１−ヒドロキシイミノプロパン誘導体及びその製造法
FI101962B (fi)	1998-09-30	Välituotteet kinoliini-3-karboksyylihappojohdannaisten valmistamiseksi
JPH0525159A (ja)	1993-02-02	２−オキソ−５−ヒドロキシクロマンの製造方法
KR20030034406A (ko)	2003-05-09	1-메틸인다졸-3-카르복실산의 제조방법
JPH0759561B2 (ja)	1995-06-28	１．３−ジアルキルピラゾール−４−カルボン酸誘導体の製造方法
HU201311B (en)	1990-10-28	Process for producing 4-substituted-3-methyl-1-aryl-5-aminopyrazole derivatives