CA2880299A1 - Process for the synthesis of substituted urea compounds - Google Patents
Process for the synthesis of substituted urea compounds Download PDFInfo
- Publication number
- CA2880299A1 CA2880299A1 CA2880299A CA2880299A CA2880299A1 CA 2880299 A1 CA2880299 A1 CA 2880299A1 CA 2880299 A CA2880299 A CA 2880299A CA 2880299 A CA2880299 A CA 2880299A CA 2880299 A1 CA2880299 A1 CA 2880299A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- heterocyclyl
- heteroaryl
- aryl
- substituted
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 113
- 230000008569 process Effects 0.000 title claims abstract description 110
- 150000003672 ureas Chemical class 0.000 title claims abstract description 13
- 230000015572 biosynthetic process Effects 0.000 title description 14
- 238000003786 synthesis reaction Methods 0.000 title description 10
- -1 carbamoyl halide Chemical class 0.000 claims abstract description 337
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 67
- 239000002904 solvent Substances 0.000 claims abstract description 47
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 238000006243 chemical reaction Methods 0.000 claims abstract description 35
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 35
- 238000004519 manufacturing process Methods 0.000 claims abstract description 20
- 239000004202 carbamide Substances 0.000 claims abstract description 18
- 150000002148 esters Chemical class 0.000 claims abstract description 12
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 11
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 11
- 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 abstract description 11
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 937
- 125000003118 aryl group Chemical group 0.000 claims description 677
- 125000001072 heteroaryl group Chemical group 0.000 claims description 667
- 125000003545 alkoxy group Chemical group 0.000 claims description 370
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 273
- 229910052736 halogen Inorganic materials 0.000 claims description 247
- 150000002367 halogens Chemical class 0.000 claims description 244
- 125000005842 heteroatom Chemical group 0.000 claims description 210
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 207
- 125000004104 aryloxy group Chemical group 0.000 claims description 174
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 169
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 167
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 165
- 229910006069 SO3H Inorganic materials 0.000 claims description 150
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 150
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 128
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 110
- 150000001875 compounds Chemical class 0.000 claims description 105
- 125000002950 monocyclic group Chemical group 0.000 claims description 102
- 125000001424 substituent group Chemical group 0.000 claims description 102
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 88
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 70
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 69
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 50
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 36
- 229910052757 nitrogen Inorganic materials 0.000 claims description 36
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 29
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- 150000001542 azirines Chemical class 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 24
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 23
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 19
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 239000001301 oxygen Substances 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 claims description 14
- 239000000460 chlorine Substances 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 11
- 238000007070 tosylation reaction Methods 0.000 claims description 10
- OXFSTTJBVAAALW-UHFFFAOYSA-N 1,3-dihydroimidazole-2-thione Chemical compound SC1=NC=CN1 OXFSTTJBVAAALW-UHFFFAOYSA-N 0.000 claims description 9
- ZHKJHQBOAJQXQR-UHFFFAOYSA-N 1H-azirine Chemical compound N1C=C1 ZHKJHQBOAJQXQR-UHFFFAOYSA-N 0.000 claims description 9
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 9
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 9
- 229910052701 rubidium Inorganic materials 0.000 claims description 9
- 125000003107 substituted aryl group Chemical group 0.000 claims description 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 7
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 claims description 6
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 6
- 238000002955 isolation Methods 0.000 claims description 6
- 238000007254 oxidation reaction Methods 0.000 claims description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 6
- 241000689227 Cora <basidiomycete fungus> Species 0.000 claims description 5
- 229910017711 NHRa Inorganic materials 0.000 claims description 5
- 229910003827 NRaRb Inorganic materials 0.000 claims description 5
- 230000001476 alcoholic effect Effects 0.000 claims description 5
- 230000021235 carbamoylation Effects 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- NBGMRMDAEWWFIR-UHFFFAOYSA-N imidazole-2-thione Chemical compound S=C1N=CC=N1 NBGMRMDAEWWFIR-UHFFFAOYSA-N 0.000 claims description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-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
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 claims description 4
- 150000003863 ammonium salts Chemical class 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims description 4
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 3
- 239000007868 Raney catalyst Substances 0.000 claims description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 3
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 230000022244 formylation Effects 0.000 claims description 3
- 238000006170 formylation reaction Methods 0.000 claims description 3
- 229910017604 nitric acid Inorganic materials 0.000 claims description 3
- 235000010288 sodium nitrite Nutrition 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical class C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 claims description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 2
- 150000004704 methoxides Chemical class 0.000 claims description 2
- 150000004965 peroxy acids Chemical class 0.000 claims description 2
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 34
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 32
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims 3
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 abstract description 12
- 125000000217 alkyl group Chemical group 0.000 description 897
- 229910003204 NH2 Inorganic materials 0.000 description 285
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 150
- 125000000565 sulfonamide group Chemical group 0.000 description 137
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 71
- 239000000543 intermediate Substances 0.000 description 34
- 125000003386 piperidinyl group Chemical group 0.000 description 32
- 125000000160 oxazolidinyl group Chemical group 0.000 description 31
- 125000004433 nitrogen atom Chemical group N* 0.000 description 30
- 101000983970 Conus catus Alpha-conotoxin CIB Proteins 0.000 description 24
- 125000004193 piperazinyl group Chemical group 0.000 description 19
- 235000013877 carbamide Nutrition 0.000 description 18
- 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 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 15
- 238000013459 approach Methods 0.000 description 15
- 239000002585 base Substances 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 125000002619 bicyclic group Chemical group 0.000 description 12
- 150000002430 hydrocarbons Chemical group 0.000 description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 8
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 125000003282 alkyl amino group Chemical group 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 238000005755 formation reaction Methods 0.000 description 7
- 229930195734 saturated hydrocarbon Natural products 0.000 description 7
- 102100029111 Fatty-acid amide hydrolase 1 Human genes 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 108010046094 fatty-acid amide hydrolase Proteins 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
- 150000001721 carbon Chemical group 0.000 description 5
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical class C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
- 229940126062 Compound A Drugs 0.000 description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 4
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 4
- 101000693970 Homo sapiens Scavenger receptor class A member 3 Proteins 0.000 description 4
- 102100027192 Scavenger receptor class A member 3 Human genes 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 125000005605 benzo group Chemical group 0.000 description 4
- 125000001246 bromo group Chemical group Br* 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 125000001624 naphthyl group Chemical group 0.000 description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 4
- BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical class NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 4
- 150000003222 pyridines Chemical class 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 150000001204 N-oxides Chemical class 0.000 description 3
- 108020001305 NR1 subfamily Proteins 0.000 description 3
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 239000005864 Sulphur Substances 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 3
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 3
- 150000003230 pyrimidines Chemical class 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- WEGYGNROSJDEIW-UHFFFAOYSA-N 3-Acetylpyridine Chemical compound CC(=O)C1=CC=CN=C1 WEGYGNROSJDEIW-UHFFFAOYSA-N 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical group NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 238000006282 Neber rearrangement reaction Methods 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- KMIQMFHPUJUDMC-HHARLNAUSA-N [(2r,3s,4r,5r,6s)-5-acetamido-3,4-diacetyloxy-6-propan-2-yloxyoxan-2-yl]methyl acetate Chemical compound CC(C)O[C@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1NC(C)=O KMIQMFHPUJUDMC-HHARLNAUSA-N 0.000 description 2
- 159000000021 acetate salts Chemical class 0.000 description 2
- 239000002253 acid Substances 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
- C07D213/50—Ketonic radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/53—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (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 (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261676554P | 2012-07-27 | 2012-07-27 | |
| US61/676,554 | 2012-07-27 | ||
| PCT/PT2013/000050 WO2014017938A2 (en) | 2012-07-27 | 2013-07-26 | Process for the synthesis of substituted urea compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2880299A1 true CA2880299A1 (en) | 2014-01-30 |
Family
ID=49003969
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2880299A Abandoned CA2880299A1 (en) | 2012-07-27 | 2013-07-26 | Process for the synthesis of substituted urea compounds |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20150197503A1 (OSRAM) |
| EP (1) | EP2882712A2 (OSRAM) |
| JP (1) | JP2015528013A (OSRAM) |
| CN (1) | CN104662002A (OSRAM) |
| BR (1) | BR112015001769A2 (OSRAM) |
| CA (1) | CA2880299A1 (OSRAM) |
| RU (1) | RU2015104103A (OSRAM) |
| WO (1) | WO2014017938A2 (OSRAM) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201401198D0 (en) | 2014-01-24 | 2014-03-12 | Bial Portela & Ca Sa | Process for the syntheis of substituted urea compounds |
| US10774064B2 (en) | 2016-06-02 | 2020-09-15 | Cadent Therapeutics, Inc. | Potassium channel modulators |
| HRP20220079T1 (hr) | 2017-01-23 | 2022-04-15 | Cadent Therapeutics, Inc. | Modulatori kalijevih kanala |
| AU2019227607C1 (en) | 2018-02-27 | 2023-07-20 | Incyte Corporation | Imidazopyrimidines and triazolopyrimidines as A2A / A2B inhibitors |
| MA52940A (fr) | 2018-05-18 | 2021-04-28 | Incyte Corp | Dérivés de pyrimidine fusionnés utilisés en tant qu'inhibiteurs de a2a/a2b |
| CA3105721A1 (en) | 2018-07-05 | 2020-01-09 | Incyte Corporation | Fused pyrazine derivatives as a2a / a2b inhibitors |
| CA3116339A1 (en) | 2018-10-22 | 2020-04-30 | Cadent Therapeutics, Inc. | Crystalline forms of potassium channel modulators |
| TWI829857B (zh) | 2019-01-29 | 2024-01-21 | 美商英塞特公司 | 作為a2a / a2b抑制劑之吡唑并吡啶及三唑并吡啶 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1238971A (OSRAM) * | 1968-03-02 | 1971-07-14 | ||
| DE2458965C3 (de) * | 1974-12-13 | 1979-10-11 | Bayer Ag, 5090 Leverkusen | 3-Amino-indazol-N-carbonsäure-Derivate, Verfahren zu ihrer Herstellung sowie sie enthaltende Arzneimittel |
| EP0014810A3 (en) * | 1979-01-18 | 1980-11-26 | Fbc Limited | Pesticidal pyrazoles, their production, compositions and uses, as well as intermediates and their preparation |
| GB8516573D0 (en) * | 1985-07-01 | 1985-08-07 | Janssen Pharmaceuticaa Nv | Controlling weeds |
| JPH01203368A (ja) * | 1988-02-10 | 1989-08-16 | Mitsui Petrochem Ind Ltd | チオイミダゾール誘導体 |
| JPH01203366A (ja) * | 1988-02-10 | 1989-08-16 | Mitsui Petrochem Ind Ltd | Ｎ−置換イミダゾール誘導体 |
| FR2674855B1 (fr) * | 1991-04-03 | 1994-01-14 | Synthelabo | Derives de piperidine, leur preparation et leur application en therapeutique. |
| CA2146755A1 (en) * | 1992-10-28 | 1994-05-11 | Kenji Takeda | Novel 1,2-benzoisoxazole derivative or its salt and brain-protecting agent comprising the same |
| US20030203862A1 (en) * | 1998-03-26 | 2003-10-30 | Miraglia Loren J. | Antisense modulation of MDM2 expression |
| EP1212416A2 (en) * | 1999-08-31 | 2002-06-12 | Ribozyme Pharmaceuticals, Inc. | Nucleic acid based modulators of gene expression |
| EP1432690A2 (en) * | 2001-04-16 | 2004-06-30 | Tanabe Seiyaku Co., Ltd. | Imidazole, thiazole and oxazole derivatives and their use for the manufacture of a medicament for the treatment and/or prevention of pollakiuria or urinary incontinence |
| US7329662B2 (en) * | 2003-10-03 | 2008-02-12 | Hoffmann-La Roche Inc. | Pyrazolo-pyridine |
| DE102004005172A1 (de) * | 2004-02-02 | 2005-08-18 | Aventis Pharma Deutschland Gmbh | Indazolderivate als Inhibitoren der Hormon Sensitiven Lipase |
| CN100424089C (zh) * | 2006-01-18 | 2008-10-08 | 中国药科大学 | 一种制备大环内酯类半合成抗生素泰利霉素的方法 |
| TWI469979B (zh) * | 2008-12-24 | 2015-01-21 | Bial Portela & Ca Sa | 脂肪酸醯胺水解酶(faah)抑制劑、以及其藥學組成物與用途 |
| BR112013001721A2 (pt) * | 2010-07-29 | 2016-05-31 | Bial Portela & Ca Sa | processo de síntese de compostos de ureia substituída |
-
2013
- 2013-07-26 EP EP13750964.2A patent/EP2882712A2/en not_active Withdrawn
- 2013-07-26 BR BR112015001769A patent/BR112015001769A2/pt not_active IP Right Cessation
- 2013-07-26 RU RU2015104103A patent/RU2015104103A/ru not_active Application Discontinuation
- 2013-07-26 CA CA2880299A patent/CA2880299A1/en not_active Abandoned
- 2013-07-26 WO PCT/PT2013/000050 patent/WO2014017938A2/en not_active Ceased
- 2013-07-26 US US14/417,354 patent/US20150197503A1/en not_active Abandoned
- 2013-07-26 CN CN201380050477.4A patent/CN104662002A/zh active Pending
- 2013-07-26 JP JP2015524222A patent/JP2015528013A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2015528013A (ja) | 2015-09-24 |
| RU2015104103A (ru) | 2016-09-20 |
| WO2014017938A2 (en) | 2014-01-30 |
| WO2014017938A3 (en) | 2014-03-20 |
| EP2882712A2 (en) | 2015-06-17 |
| CN104662002A (zh) | 2015-05-27 |
| US20150197503A1 (en) | 2015-07-16 |
| BR112015001769A2 (pt) | 2017-08-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20190726 |