BG108524A - М...'од за пол"-аван... на ра-...ми-ни и ...нан'иом...рно -и''и производни на 1,5-диарил-3-'ри"л"ором...'ил-д...л'а2 пиразолини - Google Patents

М...'од за пол"-аван... на ра-...ми-ни и ...нан'иом...рно -и''и производни на 1,5-диарил-3-'ри"л"ором...'ил-д...л'а2 пиразолини Download PDF

Info

Publication number: BG108524A
Authority: BG; Bulgaria
Prior art keywords: group; substituents; methyl; trifluoromethyl; hydrogen
Prior art date: 2001-06-18

Application number

BG108524A

Other languages

Bulgarian (bg)

English (en)

Inventor

Monserrat Alcon-Marrugat

Miguel A. Pericas-Brondo

Maria R. Cuberes-Altisen

Jordi Frigola-Constansa

Original Assignee

Laboratorios Del Dr.esteve S.А.

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.)

2001-06-18

Filing date

2004-01-13

Publication date

2004-08-31

2004-01-13 Application filed by Laboratorios Del Dr.esteve S.А. filed Critical Laboratorios Del Dr.esteve S.А.

2004-08-31 Publication of BG108524A publication Critical patent/BG108524A/bg

Links

238000000034 method Methods 0.000 title claims abstract description 34
239000000203 mixture Substances 0.000 claims abstract description 52
125000001424 substituent group Chemical group 0.000 claims abstract description 32
150000001875 compounds Chemical class 0.000 claims abstract description 29
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 29
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 28
238000002360 preparation method Methods 0.000 claims abstract description 28
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 25
239000000460 chlorine Substances 0.000 claims abstract description 25
229910052801 chlorine Inorganic materials 0.000 claims abstract description 25
229910052731 fluorine Inorganic materials 0.000 claims abstract description 25
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
239000001257 hydrogen Substances 0.000 claims abstract description 25
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 25
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 17
-1 methoxy, trifluoromethoxy, methylsulphonyl Chemical group 0.000 claims abstract description 17
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract 9
239000011737 fluorine Substances 0.000 claims abstract 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 75
239000011734 sodium Substances 0.000 claims description 45
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 42
KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 claims description 42
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 36
239000002904 solvent Substances 0.000 claims description 35
150000003839 salts Chemical class 0.000 claims description 32
KWGRBVOPPLSCSI-PSASIEDQSA-N (1s,2r)-2-(methylamino)-1-phenylpropan-1-ol Chemical compound CN[C@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-PSASIEDQSA-N 0.000 claims description 31
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
229910052708 sodium Inorganic materials 0.000 claims description 28
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 27
238000000926 separation method Methods 0.000 claims description 26
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 25
KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 claims description 20
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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 claims description 20
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 18
238000006243 chemical reaction Methods 0.000 claims description 18
DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 claims description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 17
125000001153 fluoro group Chemical group F* 0.000 claims description 16
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 16
230000015572 biosynthetic process Effects 0.000 claims description 14
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 12
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 10
239000001099 ammonium carbonate Substances 0.000 claims description 10
235000012501 ammonium carbonate Nutrition 0.000 claims description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 9
238000010992 reflux Methods 0.000 claims description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
229910021529 ammonia Inorganic materials 0.000 claims description 8
JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 claims description 8
235000010265 sodium sulphite Nutrition 0.000 claims description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 7
239000002609 medium Substances 0.000 claims description 7
KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 6
230000002378 acidificating effect Effects 0.000 claims description 5
238000009835 boiling Methods 0.000 claims description 5
229960002179 ephedrine Drugs 0.000 claims description 5
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 claims description 5
229940067157 phenylhydrazine Drugs 0.000 claims description 5
159000000000 sodium salts Chemical class 0.000 claims description 5
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
239000012736 aqueous medium Substances 0.000 claims description 4
238000002425 crystallisation Methods 0.000 claims description 4
230000008025 crystallization Effects 0.000 claims description 4
150000003219 pyrazolines Chemical class 0.000 claims description 4
230000003287 optical effect Effects 0.000 claims description 3
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 6
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical group ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims 4
230000003993 interaction Effects 0.000 claims 3
125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 claims 2
125000000542 sulfonic acid group Chemical group 0.000 claims 2
230000001476 alcoholic effect Effects 0.000 claims 1
FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 claims 1
150000007522 mineralic acids Chemical class 0.000 claims 1
125000004429 atom Chemical group 0.000 abstract 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
235000019441 ethanol Nutrition 0.000 description 15
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 14
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
238000005755 formation reaction Methods 0.000 description 11
239000002244 precipitate Substances 0.000 description 10
238000001953 recrystallisation Methods 0.000 description 7
239000000243 solution Substances 0.000 description 7
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 6
239000011780 sodium chloride Substances 0.000 description 6
239000002253 acid Substances 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000007787 solid Substances 0.000 description 5
229940124530 sulfonamide Drugs 0.000 description 5
150000003456 sulfonamides Chemical class 0.000 description 5
125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 4
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
DOUHZFSGSXMPIE-UHFFFAOYSA-N hydroxidooxidosulfur(.) Chemical compound [O]SO DOUHZFSGSXMPIE-UHFFFAOYSA-N 0.000 description 4
239000012071 phase Substances 0.000 description 4
238000001556 precipitation Methods 0.000 description 4
239000000047 product Substances 0.000 description 4
239000012429 reaction media Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
ZHYAENSFCNMJQQ-UHFFFAOYSA-N (4-methylsulfonylphenyl)hydrazine Chemical compound CS(=O)(=O)C1=CC=C(NN)C=C1 ZHYAENSFCNMJQQ-UHFFFAOYSA-N 0.000 description 3
MCGBIXXDQFWVDW-UHFFFAOYSA-N 4,5-dihydro-1h-pyrazole Chemical class C1CC=NN1 MCGBIXXDQFWVDW-UHFFFAOYSA-N 0.000 description 3
NBJSNAGTUCWQRO-UHFFFAOYSA-N 4-hydrazinylbenzenesulfonamide Chemical compound NNC1=CC=C(S(N)(=O)=O)C=C1 NBJSNAGTUCWQRO-UHFFFAOYSA-N 0.000 description 3
UFQITJHITOYXHL-UHFFFAOYSA-N C1=CC(S(=O)(=O)O)=CC=C1C1N(C=2C(=CC(F)=CC=2)F)N=C(C(F)(F)F)C1 Chemical compound C1=CC(S(=O)(=O)O)=CC=C1C1N(C=2C(=CC(F)=CC=2)F)N=C(C(F)(F)F)C1 UFQITJHITOYXHL-UHFFFAOYSA-N 0.000 description 3
229910006074 SO2NH2 Inorganic materials 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
239000012043 crude product Substances 0.000 description 3
BALXUFOVQVENIU-GHXDPTCOSA-N hydron;(1s,2r)-2-(methylamino)-1-phenylpropan-1-ol;chloride Chemical compound Cl.CN[C@H](C)[C@@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-GHXDPTCOSA-N 0.000 description 3
238000003756 stirring Methods 0.000 description 3
238000006277 sulfonation reaction Methods 0.000 description 3
QOCDZDDDUCWJFM-DUXPYHPUSA-N (e)-4-(2,4-difluorophenyl)-1,1,1-trifluorobut-3-en-2-one Chemical compound FC1=CC=C(\C=C\C(=O)C(F)(F)F)C(F)=C1 QOCDZDDDUCWJFM-DUXPYHPUSA-N 0.000 description 2
UTWMSGSDWZDPOM-UHFFFAOYSA-N 2-methyl-3-phenylcyclobutan-1-one Chemical compound C1C(=O)C(C)C1C1=CC=CC=C1 UTWMSGSDWZDPOM-UHFFFAOYSA-N 0.000 description 2
PCPUKVSTMLHXQF-UHFFFAOYSA-N 4-formylbenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(C=O)C=C1 PCPUKVSTMLHXQF-UHFFFAOYSA-N 0.000 description 2
PSVPUHBSBYJSMQ-UHFFFAOYSA-N 4-methylsulfonylbenzaldehyde Chemical compound CS(=O)(=O)C1=CC=C(C=O)C=C1 PSVPUHBSBYJSMQ-UHFFFAOYSA-N 0.000 description 2
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 2
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
102000010907 Cyclooxygenase 2 Human genes 0.000 description 2
108010037462 Cyclooxygenase 2 Proteins 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
238000005904 alkaline hydrolysis reaction Methods 0.000 description 2
239000002260 anti-inflammatory agent Substances 0.000 description 2
229940121363 anti-inflammatory agent Drugs 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
229940077388 benzenesulfonate Drugs 0.000 description 2
238000001816 cooling Methods 0.000 description 2
UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
238000001914 filtration Methods 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
238000002156 mixing Methods 0.000 description 2
238000000746 purification Methods 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
150000003460 sulfonic acids Chemical class 0.000 description 2
HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
DKLYUPYGWKBDGD-QPJJXVBHSA-N (e)-1,1,1-trifluoro-4-(4-methylsulfonylphenyl)but-3-en-2-one Chemical compound CS(=O)(=O)C1=CC=C(\C=C\C(=O)C(F)(F)F)C=C1 DKLYUPYGWKBDGD-QPJJXVBHSA-N 0.000 description 1
ORZMSMCZBZARKY-UHFFFAOYSA-N 1,3,2$l^{6}-benzodioxathiole 2,2-dioxide Chemical compound C1=CC=C2OS(=O)(=O)OC2=C1 ORZMSMCZBZARKY-UHFFFAOYSA-N 0.000 description 1
NUUXNKLZACNVSR-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-3-(4-methylsulfonylphenyl)-5-(trifluoromethyl)-3,4-dihydropyrazole Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1N(C=2C(=CC(F)=CC=2)F)N=C(C(F)(F)F)C1 NUUXNKLZACNVSR-UHFFFAOYSA-N 0.000 description 1
PQKMMIXPTSZZAU-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-3-phenyl-5-(trifluoromethyl)-3,4-dihydropyrazole Chemical compound FC1=CC(F)=CC=C1N1C(C=2C=CC=CC=2)CC(C(F)(F)F)=N1 PQKMMIXPTSZZAU-UHFFFAOYSA-N 0.000 description 1
VZFSOJKXOOEGCQ-UHFFFAOYSA-N 3-(2,4-difluorophenyl)-2-phenyl-5-(trifluoromethyl)-3,4-dihydropyrazole Chemical compound FC1=CC(F)=CC=C1C1N(C=2C=CC=CC=2)N=C(C(F)(F)F)C1 VZFSOJKXOOEGCQ-UHFFFAOYSA-N 0.000 description 1
YNWVUSWKOYRCGV-ZZXKWVIFSA-N 4-[(e)-4,4,4-trifluoro-3-oxobut-1-enyl]benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(\C=C\C(=O)C(F)(F)F)C=C1 YNWVUSWKOYRCGV-ZZXKWVIFSA-N 0.000 description 1
ZZMJXWXXMAAPLI-UHFFFAOYSA-N 4-[3-(2,4-difluorophenyl)-5-(trifluoromethyl)-3,4-dihydropyrazol-2-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(C=2C(=CC(F)=CC=2)F)CC(C(F)(F)F)=N1 ZZMJXWXXMAAPLI-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
BALXUFOVQVENIU-GNAZCLTHSA-N Ephedrine hydrochloride Chemical compound Cl.CN[C@@H](C)[C@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-GNAZCLTHSA-N 0.000 description 1
101000592466 Homo sapiens Proteasome subunit beta type-4 Proteins 0.000 description 1
102100033190 Proteasome subunit beta type-4 Human genes 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
150000003935 benzaldehydes Chemical class 0.000 description 1
RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 1
RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000003814 drug Substances 0.000 description 1
DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 1
238000000605 extraction Methods 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
231100000414 gastrointestinal toxicity Toxicity 0.000 description 1
238000011141 high resolution liquid chromatography Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
231100000417 nephrotoxicity Toxicity 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
239000002245 particle Substances 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
150000004031 phenylhydrazines Chemical class 0.000 description 1
125000002755 pyrazolinyl group Chemical group 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
RLUJQBLWUQZMDG-UHFFFAOYSA-N toluene;hydrochloride Chemical compound Cl.CC1=CC=CC=C1 RLUJQBLWUQZMDG-UHFFFAOYSA-N 0.000 description 1
238000005406 washing Methods 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
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

BG108524A 2001-06-18 2004-01-13 М...'од за пол"-аван... на ра-...ми-ни и ...нан'иом...рно -и''и производни на 1,5-диарил-3-'ри"л"ором...'ил-д...л'а2 пиразолини BG108524A (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
ES200101412A ES2183720B1 (es)	2001-06-18	2001-06-18	Procedimiento para la preparacion de derivados de 1,5-diaril-3-trifluorometil-delta2-pirazolinas racemicas y enantiomericamente puras.
PCT/ES2002/000274 WO2002102781A1 (fr)	2001-06-18	2002-06-06	Procede de preparation de derives de 1,5-diaryl-3-trifluoromethyl-delta2-pyrazolines racemiques et pures du point de vue enantiomerique

Publications (1)

Publication Number	Publication Date
BG108524A true BG108524A (bg)	2004-08-31

Family

ID=8498105

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG108524A BG108524A (bg)	2001-06-18	2004-01-13	М...'од за пол"-аван... на ра-...ми-ни и ...нан'иом...рно -и''и производни на 1,5-диарил-3-'ри"л"ором...'ил-д...л'а2 пиразолини

Country Status (26)

Country	Link
US (3)	US6846935B2 (fr)
EP (1)	EP1408035B1 (fr)
JP (1)	JP2005502604A (fr)
KR (1)	KR20040018275A (fr)
CN (1)	CN1275946C (fr)
AR (1)	AR036050A1 (fr)
AT (1)	ATE315030T1 (fr)
BG (1)	BG108524A (fr)
BR (1)	BR0211009A (fr)
CA (1)	CA2451132C (fr)
CZ (1)	CZ200481A3 (fr)
DE (1)	DE60208551T2 (fr)
DK (1)	DK1408035T3 (fr)
EE (1)	EE200400016A (fr)
ES (2)	ES2183720B1 (fr)
HU (1)	HUP0401715A3 (fr)
IL (1)	IL159367A0 (fr)
MX (1)	MXPA03011783A (fr)
NO (1)	NO20035642L (fr)
PL (1)	PL367773A1 (fr)
PT (1)	PT1408035E (fr)
RU (1)	RU2288915C2 (fr)
SI (1)	SI1408035T1 (fr)
SK (1)	SK422004A3 (fr)
WO (1)	WO2002102781A1 (fr)
ZA (1)	ZA200400343B (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2183720B1 (es) *	2001-06-18	2004-01-16	Esteve Labor Dr	Procedimiento para la preparacion de derivados de 1,5-diaril-3-trifluorometil-delta2-pirazolinas racemicas y enantiomericamente puras.
WO2005120584A2 (fr) *	2004-06-03	2005-12-22	The Trustees Of Columbia University In The City Of New York	Composes a base d'arylsulfonyle radiomarques et leurs applications
DE102004057303A1 (de)	2004-11-26	2006-06-01	Merck Patent Gmbh	Stabile Kristallmodifikationen von DOTAP Chlorid
EP1757587A1 (fr) *	2005-07-15	2007-02-28	Laboratorios Del Dr. Esteve, S.A.	Composés de pyrazoline substituée, leur préparation et leur usage comme médicaments
US9376420B2 (en) *	2012-10-25	2016-06-28	Yuhan Corporation	4,5-dihydro-1H-pyrazole derivative or salts thereof, and pharmaceutical composition comprising same

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BE788658R (fr) *	1971-09-09	1973-03-12	Hoechst Ag	Derives de 3-(3', 4'-dichloro-6'-alkylphenyl) -delta2-pyrazolines, leurpreparation et leur utilisation comme agents d'azurage
ES2137138B1 (es) *	1998-05-29	2000-09-16	Esteve Labor Dr	Derivados de pirazolinas, su preparacion y su aplicacion como medicamentos.
AU771668C (en) *	1999-06-16	2005-08-11	Temple University - Of The Commonwealth System Of Higher Education	1-(4-sulfamylaryl)-3-substituted-5-aryl-2-pyrazolines as inhibitors of cyclooxygenase-2
ES2183720B1 (es) *	2001-06-18	2004-01-16	Esteve Labor Dr	Procedimiento para la preparacion de derivados de 1,5-diaril-3-trifluorometil-delta2-pirazolinas racemicas y enantiomericamente puras.

2001
- 2001-06-18 ES ES200101412A patent/ES2183720B1/es not_active Expired - Fee Related
2002
- 2002-06-06 DK DK02735442T patent/DK1408035T3/da active
- 2002-06-06 EP EP02735442A patent/EP1408035B1/fr not_active Expired - Lifetime
- 2002-06-06 SK SK42-2004A patent/SK422004A3/sk unknown
- 2002-06-06 US US10/312,194 patent/US6846935B2/en not_active Expired - Fee Related
- 2002-06-06 SI SI200230277T patent/SI1408035T1/sl unknown
- 2002-06-06 PL PL02367773A patent/PL367773A1/xx not_active Application Discontinuation
- 2002-06-06 CZ CZ200481A patent/CZ200481A3/cs unknown
- 2002-06-06 EE EEP200400016A patent/EE200400016A/xx unknown
- 2002-06-06 CN CNB028143280A patent/CN1275946C/zh not_active Expired - Fee Related
- 2002-06-06 KR KR10-2003-7016500A patent/KR20040018275A/ko not_active Ceased
- 2002-06-06 HU HU0401715A patent/HUP0401715A3/hu unknown
- 2002-06-06 IL IL15936702A patent/IL159367A0/xx unknown
- 2002-06-06 WO PCT/ES2002/000274 patent/WO2002102781A1/fr not_active Ceased
- 2002-06-06 AT AT02735442T patent/ATE315030T1/de active
- 2002-06-06 ES ES02735442T patent/ES2256483T3/es not_active Expired - Lifetime
- 2002-06-06 PT PT02735442T patent/PT1408035E/pt unknown
- 2002-06-06 DE DE60208551T patent/DE60208551T2/de not_active Expired - Lifetime
- 2002-06-06 MX MXPA03011783A patent/MXPA03011783A/es active IP Right Grant
- 2002-06-06 JP JP2003505323A patent/JP2005502604A/ja active Pending
- 2002-06-06 CA CA2451132A patent/CA2451132C/fr not_active Expired - Fee Related
- 2002-06-06 RU RU2004101050/04A patent/RU2288915C2/ru not_active IP Right Cessation
- 2002-06-06 BR BR0211009-1A patent/BR0211009A/pt not_active IP Right Cessation
- 2002-06-12 AR ARP020102218A patent/AR036050A1/es not_active Application Discontinuation
2003
- 2003-12-17 NO NO20035642A patent/NO20035642L/no not_active Application Discontinuation
2004
- 2004-01-13 BG BG108524A patent/BG108524A/bg unknown
- 2004-01-16 ZA ZA2004/00343A patent/ZA200400343B/en unknown
- 2004-12-08 US US11/006,931 patent/US20050096474A1/en not_active Abandoned
- 2004-12-08 US US11/007,449 patent/US6958403B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
DE60208551D1 (de)	2006-03-30
US20050096373A1 (en)	2005-05-05
BR0211009A (pt)	2004-11-03
HUP0401715A2 (hu)	2005-01-28
NO20035642D0 (no)	2003-12-17
RU2004101050A (ru)	2005-06-27
PT1408035E (pt)	2006-05-31
SI1408035T1 (sl)	2006-04-30
CN1610672A (zh)	2005-04-27
US6846935B2 (en)	2005-01-25
CZ200481A3 (cs)	2004-07-14
NO20035642L (no)	2004-02-12
JP2005502604A (ja)	2005-01-27
SK422004A3 (en)	2004-07-07
ES2183720B1 (es)	2004-01-16
EP1408035B1 (fr)	2006-01-04
DE60208551T2 (de)	2006-10-19
ES2256483T3 (es)	2006-07-16
CA2451132C (fr)	2010-10-12
KR20040018275A (ko)	2004-03-02
HUP0401715A3 (en)	2005-06-28
WO2002102781A1 (fr)	2002-12-27
RU2288915C2 (ru)	2006-12-10
EP1408035A1 (fr)	2004-04-14
MXPA03011783A (es)	2004-04-02
US20040019222A1 (en)	2004-01-29
ES2183720A1 (es)	2003-03-16
HK1077058A1 (en)	2006-02-03
ZA200400343B (en)	2005-03-30
IL159367A0 (en)	2004-06-01
EE200400016A (et)	2004-04-15
DK1408035T3 (da)	2006-05-08
ATE315030T1 (de)	2006-02-15
US6958403B2 (en)	2005-10-25
US20050096474A1 (en)	2005-05-05
AR036050A1 (es)	2004-08-04
CN1275946C (zh)	2006-09-20
CA2451132A1 (fr)	2002-12-27
PL367773A1 (en)	2005-03-07

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JPH08198840A (ja)	1996-08-06	Ｎ−置換−ｎ−スルホニルアミド類の製造方法
JPH02202885A (ja)	1990-08-10	ピラゾリン化合物の光学分割方法
JPS6163659A (ja)	1986-04-01	４−（２，４−ジクロルベンゾイル）−１−メチル−５−ヒドロキシピラゾ−ルの製造法
JPH0477471A (ja)	1992-03-11	５―アミノ―１ｈ―ピラゾール化合物の製造方法
JPH02295975A (ja)	1990-12-06	３―ｎ―モノ置換アミノ―４―置換―５―ピラゾロン類の製造方法
HU219351B (en)	2001-03-28	Process for producing n-sulfonilamino phenyl ketone derivatives
CH527825A (fr)	1972-09-15	Procédé de fabrication de composés présentant une action thérapeutique
JPH05294942A (ja)	1993-11-09	３（２ｈ）−ピリダジノン誘導体の製造方法
JPH0812655A (ja)	1996-01-16	置換アセチル化合物
BE546776A (fr)