SK15052000A3 - Spôsob výroby pyrazolo[4,3-d]pyrimidin-7-ón-3-pyridylsulfonylových zlúčenín a medziprodukty pre tento spôsob - Google Patents
Spôsob výroby pyrazolo[4,3-d]pyrimidin-7-ón-3-pyridylsulfonylových zlúčenín a medziprodukty pre tento spôsob Download PDFInfo
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- SK15052000A3 SK15052000A3 SK1505-2000A SK15052000A SK15052000A3 SK 15052000 A3 SK15052000 A3 SK 15052000A3 SK 15052000 A SK15052000 A SK 15052000A SK 15052000 A3 SK15052000 A3 SK 15052000A3
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- 238000000034 method Methods 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title claims abstract description 33
- 239000000543 intermediate Substances 0.000 title claims description 28
- 150000001875 compounds Chemical class 0.000 claims abstract description 269
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims abstract description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 82
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 65
- 239000002904 solvent Substances 0.000 claims description 61
- 238000006243 chemical reaction Methods 0.000 claims description 55
- -1 C 1 -C 4 alkoxy Chemical group 0.000 claims description 42
- 239000000203 mixture Substances 0.000 claims description 40
- 125000004432 carbon atom Chemical group C* 0.000 claims description 33
- 239000002516 radical scavenger Substances 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 31
- 239000003795 chemical substances by application Substances 0.000 claims description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 17
- 239000012442 inert solvent Substances 0.000 claims description 16
- 229910052751 metal Inorganic materials 0.000 claims description 16
- 239000002184 metal Substances 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 125000006239 protecting group Chemical group 0.000 claims description 12
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 11
- 230000015572 biosynthetic process Effects 0.000 claims description 11
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 11
- 239000012351 deprotecting agent Substances 0.000 claims description 11
- 239000000460 chlorine Substances 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 claims description 8
- UEYQJQVBUVAELZ-UHFFFAOYSA-N 2-Hydroxynicotinic acid Chemical compound OC(=O)C1=CC=CN=C1O UEYQJQVBUVAELZ-UHFFFAOYSA-N 0.000 claims description 7
- 150000002148 esters Chemical group 0.000 claims description 7
- 230000003301 hydrolyzing effect Effects 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 238000002955 isolation Methods 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000008096 xylene Substances 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 4
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 229910052987 metal hydride Inorganic materials 0.000 claims description 4
- 150000004681 metal hydrides Chemical class 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 230000000269 nucleophilic effect Effects 0.000 claims description 4
- 125000005936 piperidyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 claims description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 3
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 3
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 229910044991 metal oxide Inorganic materials 0.000 claims description 3
- 150000004706 metal oxides Chemical class 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 3
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 claims description 2
- 239000000010 aprotic solvent Substances 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000002393 azetidinyl group Chemical group 0.000 claims description 2
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 239000012954 diazonium Substances 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical group [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 claims description 2
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000001453 quaternary ammonium group Chemical group 0.000 claims 2
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 claims 1
- XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-O oxonium Chemical group [OH3+] XLYOFNOQVPJJNP-UHFFFAOYSA-O 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- 239000002585 base Substances 0.000 description 50
- 239000000243 solution Substances 0.000 description 38
- 239000011541 reaction mixture Substances 0.000 description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- 239000007787 solid Substances 0.000 description 31
- 235000002639 sodium chloride Nutrition 0.000 description 28
- 238000010992 reflux Methods 0.000 description 21
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 20
- 239000000725 suspension Substances 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 13
- 125000003158 alcohol group Chemical group 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
- HHEIMYAXCOIQCJ-UHFFFAOYSA-N ethyl 2,2-dimethylpropanoate Chemical compound CCOC(=O)C(C)(C)C HHEIMYAXCOIQCJ-UHFFFAOYSA-N 0.000 description 7
- XLLIQLLCWZCATF-UHFFFAOYSA-N 2-methoxyethyl acetate Chemical compound COCCOC(C)=O XLLIQLLCWZCATF-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 150000004703 alkoxides Chemical class 0.000 description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- PCRIWLRXFJTJPJ-UHFFFAOYSA-N 2-ethoxy-5-(4-ethylpiperazin-1-yl)sulfonylpyridine-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(OCC)=NC=C1S(=O)(=O)N1CCN(CC)CC1 PCRIWLRXFJTJPJ-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 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 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 4
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 4
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 4
- 239000012038 nucleophile Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 4
- ZUWITCSMJULFEU-UHFFFAOYSA-N 2-oxo-5-sulfo-1h-pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC(S(O)(=O)=O)=CNC1=O ZUWITCSMJULFEU-UHFFFAOYSA-N 0.000 description 3
- UCYSPAFCTNOUFA-UHFFFAOYSA-N 4-amino-5-ethyl-1-(pyridin-2-ylmethyl)pyrazole-3-carboxamide Chemical compound CCC1=C(N)C(C(N)=O)=NN1CC1=CC=CC=N1 UCYSPAFCTNOUFA-UHFFFAOYSA-N 0.000 description 3
- BXIIVRFUQABYFR-UHFFFAOYSA-N 5-ethoxycarbonyl-6-oxo-1h-pyridine-3-sulfonic acid Chemical compound CCOC(=O)C1=CC(S(O)(=O)=O)=CN=C1O BXIIVRFUQABYFR-UHFFFAOYSA-N 0.000 description 3
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000007822 coupling agent Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 239000012456 homogeneous solution Substances 0.000 description 3
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- ZEHWELRKYFJZHY-UHFFFAOYSA-N n-[3-carbamoyl-5-ethyl-1-(pyridin-2-ylmethyl)pyrazol-4-yl]-2-ethoxy-5-(4-ethylpiperazin-1-yl)sulfonylpyridine-3-carboxamide Chemical compound CCOC1=NC=C(S(=O)(=O)N2CCN(CC)CC2)C=C1C(=O)NC(C(=N1)C(N)=O)=C(CC)N1CC1=CC=CC=N1 ZEHWELRKYFJZHY-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 239000013557 residual solvent Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 2
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Reproductive Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Gynecology & Obstetrics (AREA)
- Endocrinology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9924042.6A GB9924042D0 (en) | 1999-10-11 | 1999-10-11 | Process for thr preparation of pyrazolo[4,3-D]pyrimidin-7-ones-3-pyridylsulphonyl compounds and intermediates thereof |
| GB0018667A GB0018667D0 (en) | 2000-07-28 | 2000-07-28 | Process for the preparation of pyrazolo [4,3-d] Pyrimidin-7-ones-3-pyridylsulphonyl compounds and intermediates thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK15052000A3 true SK15052000A3 (sk) | 2003-01-09 |
Family
ID=26244761
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1505-2000A SK15052000A3 (sk) | 1999-10-11 | 2000-10-09 | Spôsob výroby pyrazolo[4,3-d]pyrimidin-7-ón-3-pyridylsulfonylových zlúčenín a medziprodukty pre tento spôsob |
Country Status (39)
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI265925B (en) | 1999-10-11 | 2006-11-11 | Pfizer | Pyrazolo[4,3-d]pyrimidin-7-ones useful in inhibiting type 5 cyclic guanosine 3',5'-monophosphate phosphodiesterases(cGMP PDE5), process and intermediates for their preparation, their uses and composition comprising them |
| YU59100A (sh) * | 1999-10-11 | 2003-10-31 | Pfizer Inc. | Postupak za dobijanje pirazolo (4,3-d) pirimidin-7-ona-3-piridilsulfonil jedinjenja i njihova intermedijera |
| US6809200B2 (en) * | 2000-07-28 | 2004-10-26 | Pfizer Inc. | Process for the preparation of pyrazolo[4,3-d]pyrimidin-7-one compounds and intermediates thereof |
| JP2006219373A (ja) * | 2003-06-13 | 2006-08-24 | Daiichi Asubio Pharma Co Ltd | Ｐｄｅ７阻害作用を有するピリジニルピラゾロピリミジノン誘導体 |
| WO2007057316A2 (en) * | 2005-11-16 | 2007-05-24 | F. Hoffmann-La Roche Ag | Novel process for the preparation of thoc |
| KR101002490B1 (ko) * | 2007-06-09 | 2010-12-17 | 동아제약주식회사 | 유데나필을 유효성분으로 함유하는 만성 심부전증 치료용약학적 조성물 |
| AP2013007070A0 (en) * | 2011-02-23 | 2013-08-31 | Pfizer | Imidazo[5,1-f][1,2,4] triazines for the treatment of neurological disorders |
| EP3541787A1 (en) * | 2016-11-21 | 2019-09-25 | Adama Agan Ltd. | Process for preparing methoxy methyl pyridine dicarboxylate |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ299633B6 (cs) * | 1997-04-25 | 2008-09-24 | Pfizer Inc. | Pyrazolopyrimidinony, meziprodukty pro jejich výrobu a farmaceutické a veterinární kompozice na jejich bázi |
| ATE247117T1 (de) * | 1998-04-20 | 2003-08-15 | Pfizer | Pyrazolopyrimidinone cgmp pde5 inhibitoren zur behandlung von sexualfunktionsstörungen |
| GB9823101D0 (en) * | 1998-10-23 | 1998-12-16 | Pfizer Ltd | Pharmaceutically active compounds |
| KR100353014B1 (ko) * | 1998-11-11 | 2002-09-18 | 동아제약 주식회사 | 발기부전 치료에 효과를 갖는 피라졸로피리미디논 화합물 |
| YU59100A (sh) * | 1999-10-11 | 2003-10-31 | Pfizer Inc. | Postupak za dobijanje pirazolo (4,3-d) pirimidin-7-ona-3-piridilsulfonil jedinjenja i njihova intermedijera |
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2000
- 2000-09-29 YU YU59100A patent/YU59100A/sh unknown
- 2000-10-05 IL IL13891300A patent/IL138913A0/xx unknown
- 2000-10-06 OA OA1200000272A patent/OA11495A/en unknown
- 2000-10-06 CA CA002322995A patent/CA2322995A1/en not_active Abandoned
- 2000-10-09 ID IDP20000871D patent/ID27539A/id unknown
- 2000-10-09 EG EG20001282A patent/EG22775A/xx active
- 2000-10-09 SK SK1505-2000A patent/SK15052000A3/sk unknown
- 2000-10-09 SG SG200005769A patent/SG97950A1/en unknown
- 2000-10-10 AR ARP000105334A patent/AR029767A1/es not_active Application Discontinuation
- 2000-10-10 PA PA20008504601A patent/PA8504601A1/es unknown
- 2000-10-10 GT GT200000169A patent/GT200000169A/es unknown
- 2000-10-10 EA EA200000924A patent/EA003145B1/ru not_active IP Right Cessation
- 2000-10-10 IS IS5654A patent/IS5654A/is unknown
- 2000-10-10 EP EP00308915A patent/EP1092720B1/en not_active Expired - Lifetime
- 2000-10-10 MX MXPA00009936A patent/MXPA00009936A/es active IP Right Grant
- 2000-10-10 DE DE60017330T patent/DE60017330D1/de not_active Expired - Lifetime
- 2000-10-10 DZ DZ000144A patent/DZ3096A1/xx active
- 2000-10-10 TN TNTNSN00195A patent/TNSN00195A1/fr unknown
- 2000-10-10 NO NO20005104A patent/NO316072B1/no not_active IP Right Cessation
- 2000-10-10 CZ CZ20003754A patent/CZ20003754A3/cs unknown
- 2000-10-10 MA MA26085A patent/MA25867A1/fr unknown
- 2000-10-10 AT AT00308915T patent/ATE286899T1/de not_active IP Right Cessation
- 2000-10-10 KR KR20000059435A patent/KR100395718B1/ko not_active Expired - Fee Related
- 2000-10-10 UY UY26388A patent/UY26388A1/es not_active Application Discontinuation
- 2000-10-10 NZ NZ507431A patent/NZ507431A/xx unknown
- 2000-10-11 HR HR20000674A patent/HRP20000674A2/hr not_active Application Discontinuation
- 2000-10-11 HU HU0003979A patent/HUP0003979A3/hu unknown
- 2000-10-11 TR TR2000/02959A patent/TR200002959A2/xx unknown
- 2000-10-11 PL PL00343140A patent/PL343140A1/xx not_active Application Discontinuation
- 2000-10-11 BG BG104840A patent/BG104840A/bg unknown
- 2000-10-11 CO CO00077465A patent/CO5251476A1/es not_active Application Discontinuation
- 2000-10-11 AU AU65436/00A patent/AU6543600A/en not_active Abandoned
- 2000-10-11 JP JP2000310705A patent/JP2001114783A/ja not_active Withdrawn
- 2000-10-11 EE EEP200000537A patent/EE200000537A/xx unknown
- 2000-10-11 SV SV2000000194A patent/SV2002000194A/es unknown
- 2000-10-11 BR BR0004787-2A patent/BR0004787A/pt not_active IP Right Cessation
- 2000-10-11 CN CN001317067A patent/CN1292379A/zh active Pending
- 2000-10-11 PE PE2000001091A patent/PE20010682A1/es not_active Application Discontinuation
- 2000-10-16 IN IN902MU2000 patent/IN190477B/en unknown
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