ES2207464T3 - Procedimiento para preparar 8-ciclopentil-6-etil-3-(sustituido)-5,8-dihidro-4h-1,2,3a,7,8,pentaaza-as-indacenos y productos intermedios utiles en el mismo. - Google Patents
Procedimiento para preparar 8-ciclopentil-6-etil-3-(sustituido)-5,8-dihidro-4h-1,2,3a,7,8,pentaaza-as-indacenos y productos intermedios utiles en el mismo.Info
- Publication number
- ES2207464T3 ES2207464T3 ES00302947T ES00302947T ES2207464T3 ES 2207464 T3 ES2207464 T3 ES 2207464T3 ES 00302947 T ES00302947 T ES 00302947T ES 00302947 T ES00302947 T ES 00302947T ES 2207464 T3 ES2207464 T3 ES 2207464T3
- Authority
- ES
- Spain
- Prior art keywords
- formula
- compound
- reaction mixture
- ethyl
- reaction
- Prior art date
- 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 - Lifetime
Links
- 238000000034 method Methods 0.000 title claims description 93
- 239000013067 intermediate product Substances 0.000 title description 11
- -1 8-cyclopentyl-6-ethyl-3- [substituted] -5,8-dihydro-4H-1, 2, 3a, 7, 8-pentaaza-as-indacene compound Chemical class 0.000 claims abstract description 157
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 37
- 150000003839 salts Chemical group 0.000 claims abstract description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
- 239000001257 hydrogen Substances 0.000 claims abstract description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 16
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 12
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 9
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 7
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 97
- 238000006243 chemical reaction Methods 0.000 claims description 93
- 150000001875 compounds Chemical class 0.000 claims description 93
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 83
- 239000011541 reaction mixture Substances 0.000 claims description 83
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 65
- 239000000243 solution Substances 0.000 claims description 61
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 40
- 239000002253 acid Substances 0.000 claims description 35
- 239000000047 product Substances 0.000 claims description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 32
- 239000002904 solvent Substances 0.000 claims description 31
- 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 26
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 21
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 claims description 19
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 238000007254 oxidation reaction Methods 0.000 claims description 17
- 239000007787 solid Substances 0.000 claims description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 239000003054 catalyst Substances 0.000 claims description 15
- 230000003647 oxidation Effects 0.000 claims description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 14
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 14
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims description 14
- 150000001408 amides Chemical class 0.000 claims description 12
- JBFHTYHTHYHCDJ-UHFFFAOYSA-N gamma-caprolactone Chemical compound CCC1CCC(=O)O1 JBFHTYHTHYHCDJ-UHFFFAOYSA-N 0.000 claims description 12
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 239000000725 suspension Substances 0.000 claims description 11
- LKIMDXQLHFCXQF-UHFFFAOYSA-N 3-methoxy-1h-pyridin-2-one Chemical compound COC1=CC=CN=C1O LKIMDXQLHFCXQF-UHFFFAOYSA-N 0.000 claims description 10
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 239000012279 sodium borohydride Substances 0.000 claims description 10
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 239000003638 chemical reducing agent Substances 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 claims description 9
- 239000005708 Sodium hypochlorite Substances 0.000 claims description 8
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 8
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 8
- 239000007800 oxidant agent Substances 0.000 claims description 8
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 8
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
- GUGQQGROXHPINL-UHFFFAOYSA-N 2-oxobutanoyl chloride Chemical compound CCC(=O)C(Cl)=O GUGQQGROXHPINL-UHFFFAOYSA-N 0.000 claims description 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 6
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- FPQRIFDTYLBNHV-UHFFFAOYSA-N cyclopentylhydrazine;dihydrochloride Chemical compound Cl.Cl.NNC1CCCC1 FPQRIFDTYLBNHV-UHFFFAOYSA-N 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 claims description 6
- 238000007069 methylation reaction Methods 0.000 claims description 6
- SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical compound NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 5
- 230000001590 oxidative effect Effects 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 claims description 5
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 claims description 4
- ZKQDCIXGCQPQNV-UHFFFAOYSA-N Calcium hypochlorite Chemical compound [Ca+2].Cl[O-].Cl[O-] ZKQDCIXGCQPQNV-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 4
- PHIVEUQACADDGU-UHFFFAOYSA-N chembl218103 Chemical compound C1CN(C(=NN=2)C(C)(C)C)C=2C2=C1C(CC)=NN2C1CCCC1 PHIVEUQACADDGU-UHFFFAOYSA-N 0.000 claims description 4
- NXHFZUVHADJHDW-UHFFFAOYSA-N cyclopentylhydrazine Chemical compound NNC1CCCC1 NXHFZUVHADJHDW-UHFFFAOYSA-N 0.000 claims description 4
- RZMZBHSKPLVQCP-UHFFFAOYSA-N ethyl 2-amino-2-oxoacetate Chemical compound CCOC(=O)C(N)=O RZMZBHSKPLVQCP-UHFFFAOYSA-N 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- TUPZMLLDXCWVKH-UHFFFAOYSA-N pyrazolo[4,3-b]pyridin-3-one Chemical compound C1=CN=C2C(=O)N=NC2=C1 TUPZMLLDXCWVKH-UHFFFAOYSA-N 0.000 claims description 4
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- VUZNLSBZRVZGIK-UHFFFAOYSA-N 2,2,6,6-Tetramethyl-1-piperidinol Chemical compound CC1(C)CCCC(C)(C)N1O VUZNLSBZRVZGIK-UHFFFAOYSA-N 0.000 claims description 3
- 238000003436 Schotten-Baumann reaction Methods 0.000 claims description 3
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 3
- DHCOPPHTVOXDKU-UHFFFAOYSA-N Tofimilast Chemical compound C1CN2C(C=3SC=CC=3)=NN=C2C2=C1C(CC)=NN2C1CCCC1 DHCOPPHTVOXDKU-UHFFFAOYSA-N 0.000 claims description 3
- 229940077388 benzenesulfonate Drugs 0.000 claims description 3
- 239000006227 byproduct Substances 0.000 claims description 3
- 229910052792 caesium Inorganic materials 0.000 claims description 3
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 claims description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 238000000354 decomposition reaction Methods 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 230000011987 methylation Effects 0.000 claims description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 238000006482 condensation reaction Methods 0.000 claims description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 230000008569 process Effects 0.000 description 16
- 239000010410 layer Substances 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 10
- 238000000926 separation method Methods 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 8
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 8
- 239000000376 reactant Substances 0.000 description 8
- 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
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- 102000003390 tumor necrosis factor Human genes 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000011651 chromium Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 150000003951 lactams Chemical class 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 238000006798 ring closing metathesis reaction Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 150000003333 secondary alcohols Chemical class 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- AUGGAAXFJUOEJJ-UHFFFAOYSA-N 1-cyclopentyl-7-ethoxy-3-ethyl-4,5-dihydropyrazolo[3,4-c]pyridine Chemical compound C1=2C(OCC)=NCCC=2C(CC)=NN1C1CCCC1 AUGGAAXFJUOEJJ-UHFFFAOYSA-N 0.000 description 3
- BAIYDCLETZLHLQ-UHFFFAOYSA-N C1CN2C=NN=C2C2=C1C=NN2 Chemical class C1CN2C=NN=C2C2=C1C=NN2 BAIYDCLETZLHLQ-UHFFFAOYSA-N 0.000 description 3
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 206010039085 Rhinitis allergic Diseases 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- 125000003158 alcohol group Chemical group 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 125000005604 azodicarboxylate group Chemical group 0.000 description 3
- 206010006451 bronchitis Diseases 0.000 description 3
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 3
- 229910052804 chromium Inorganic materials 0.000 description 3
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- 150000003852 triazoles Chemical class 0.000 description 3
- QJLZPHIDOKBEGS-UHFFFAOYSA-N 1-cyclopentyl-3-ethyl-5,6-dihydro-4h-pyrazolo[3,4-c]pyridin-7-one Chemical compound C1CNC(=O)C2=C1C(CC)=NN2C1CCCC1 QJLZPHIDOKBEGS-UHFFFAOYSA-N 0.000 description 2
- HGQPCLVBJPSFPH-UHFFFAOYSA-N 1-cyclopentyl-3-ethyl-6-[(4-methoxyphenyl)methyl]-4,5-dihydropyrazolo[3,4-c]pyridin-7-one Chemical compound C1CN(CC=2C=CC(OC)=CC=2)C(=O)C2=C1C(CC)=NN2C1CCCC1 HGQPCLVBJPSFPH-UHFFFAOYSA-N 0.000 description 2
- JQBWAXWIIRLJRX-UHFFFAOYSA-N 1-methyl-6-(2-methylphenyl)-2h-triazine Chemical compound CN1NN=CC=C1C1=CC=CC=C1C JQBWAXWIIRLJRX-UHFFFAOYSA-N 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pulmonology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13194999P | 1999-04-30 | 1999-04-30 | |
| US131949P | 1999-04-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2207464T3 true ES2207464T3 (es) | 2004-06-01 |
Family
ID=22451736
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES00302947T Expired - Lifetime ES2207464T3 (es) | 1999-04-30 | 2000-04-07 | Procedimiento para preparar 8-ciclopentil-6-etil-3-(sustituido)-5,8-dihidro-4h-1,2,3a,7,8,pentaaza-as-indacenos y productos intermedios utiles en el mismo. |
| ES03024166T Expired - Lifetime ES2232805T3 (es) | 1999-04-30 | 2000-04-07 | Pirazolopiridinonas como intermediarios. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES03024166T Expired - Lifetime ES2232805T3 (es) | 1999-04-30 | 2000-04-07 | Pirazolopiridinonas como intermediarios. |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US6326495B2 (forum.php) |
| EP (1) | EP1048667B1 (forum.php) |
| JP (1) | JP3510560B2 (forum.php) |
| KR (1) | KR100346619B1 (forum.php) |
| CN (2) | CN1249064C (forum.php) |
| AR (1) | AR029450A1 (forum.php) |
| AT (2) | ATE282039T1 (forum.php) |
| AU (1) | AU761391B2 (forum.php) |
| BR (1) | BR0002070A (forum.php) |
| CA (1) | CA2307080C (forum.php) |
| DE (2) | DE60006026T2 (forum.php) |
| DK (2) | DK1048667T3 (forum.php) |
| ES (2) | ES2207464T3 (forum.php) |
| HU (1) | HUP0001700A3 (forum.php) |
| ID (1) | ID25705A (forum.php) |
| IL (1) | IL135809A0 (forum.php) |
| IN (1) | IN192746B (forum.php) |
| MX (1) | MXPA00004214A (forum.php) |
| PL (1) | PL339985A1 (forum.php) |
| PT (2) | PT1048667E (forum.php) |
| RU (1) | RU2189985C2 (forum.php) |
| TR (1) | TR200001161A2 (forum.php) |
| TW (1) | TWI256392B (forum.php) |
| ZA (1) | ZA200002057B (forum.php) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8541333B2 (en) | 2009-08-13 | 2013-09-24 | China Petroleum & Chemical Corporation | Catalyst component for olefin polymerization and a catalyst comprising the same |
| TWI526421B (zh) | 2010-09-08 | 2016-03-21 | 住友化學股份有限公司 | 製造嗒酮化合物的方法及其中間物 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1094303A1 (ru) * | 1982-12-24 | 1987-12-30 | Институт физико-органической химии и углехимии АН УССР | 3-Трифторметил-7-метилимидазо- @ 4,5-с @ -1,2,4-триазоло @ 4,3-а @ пиридин,обладающий спазмолитическим действием |
| US4940715A (en) * | 1988-05-17 | 1990-07-10 | Kissei Pharmaceutical Co., Ltd. | 5H-pyrazolo[4,3-A] quinolizin-5-one compounds exhibiting therapeutic activities |
| CN1048015C (zh) | 1993-07-06 | 2000-01-05 | 美国辉瑞有限公司 | 双环四氢吡唑并吡啶类化合物 |
| WO1996012720A1 (en) | 1994-10-20 | 1996-05-02 | Pfizer Inc. | Bicyclic tetrahydro pyrazolopyridines and their use as medicaments |
| ES2172583T3 (es) | 1995-06-06 | 2002-10-01 | Pfizer | 5,6-dihidro-9h-pirazol(3,4-c)-1,2,4-triazol(4,3-alfa)piridinas triciclicas. |
-
2000
- 2000-03-01 US US09/516,549 patent/US6326495B2/en not_active Expired - Fee Related
- 2000-04-07 DE DE60006026T patent/DE60006026T2/de not_active Expired - Fee Related
- 2000-04-07 ES ES00302947T patent/ES2207464T3/es not_active Expired - Lifetime
- 2000-04-07 EP EP00302947A patent/EP1048667B1/en not_active Expired - Lifetime
- 2000-04-07 DK DK00302947T patent/DK1048667T3/da active
- 2000-04-07 AT AT03024166T patent/ATE282039T1/de not_active IP Right Cessation
- 2000-04-07 PT PT00302947T patent/PT1048667E/pt unknown
- 2000-04-07 AT AT00302947T patent/ATE252582T1/de not_active IP Right Cessation
- 2000-04-07 DK DK03024166T patent/DK1380585T3/da active
- 2000-04-07 DE DE60015819T patent/DE60015819T2/de not_active Expired - Fee Related
- 2000-04-07 ES ES03024166T patent/ES2232805T3/es not_active Expired - Lifetime
- 2000-04-07 PT PT03024166T patent/PT1380585E/pt unknown
- 2000-04-24 IL IL13580900A patent/IL135809A0/xx unknown
- 2000-04-24 IN IN447DE2000 patent/IN192746B/en unknown
- 2000-04-25 TW TW089107724A patent/TWI256392B/zh not_active IP Right Cessation
- 2000-04-26 JP JP2000125351A patent/JP3510560B2/ja not_active Expired - Fee Related
- 2000-04-26 ZA ZA200002057A patent/ZA200002057B/xx unknown
- 2000-04-27 AR ARP000102007A patent/AR029450A1/es unknown
- 2000-04-27 TR TR2000/01161A patent/TR200001161A2/xx unknown
- 2000-04-28 HU HU0001700A patent/HUP0001700A3/hu unknown
- 2000-04-28 CN CNB031476457A patent/CN1249064C/zh not_active Expired - Fee Related
- 2000-04-28 CN CNB001081403A patent/CN1160353C/zh not_active Expired - Fee Related
- 2000-04-28 AU AU30180/00A patent/AU761391B2/en not_active Ceased
- 2000-04-28 CA CA002307080A patent/CA2307080C/en not_active Expired - Fee Related
- 2000-04-28 RU RU2000111018/04A patent/RU2189985C2/ru not_active IP Right Cessation
- 2000-04-28 MX MXPA00004214A patent/MXPA00004214A/es active IP Right Grant
- 2000-04-28 ID IDP20000356D patent/ID25705A/id unknown
- 2000-04-29 KR KR1020000023025A patent/KR100346619B1/ko not_active Expired - Fee Related
- 2000-04-30 PL PL00339985A patent/PL339985A1/xx not_active Application Discontinuation
- 2000-05-02 BR BR0002070-2A patent/BR0002070A/pt not_active IP Right Cessation
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