CA2602853A1 - Ring closing and related methods and intermediates - Google Patents
Ring closing and related methods and intermediates Download PDFInfo
- Publication number
- CA2602853A1 CA2602853A1 CA002602853A CA2602853A CA2602853A1 CA 2602853 A1 CA2602853 A1 CA 2602853A1 CA 002602853 A CA002602853 A CA 002602853A CA 2602853 A CA2602853 A CA 2602853A CA 2602853 A1 CA2602853 A1 CA 2602853A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- formula
- compound
- alkyl
- hydrogen
- 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 205
- 239000000543 intermediate Substances 0.000 title abstract description 23
- 150000001875 compounds Chemical class 0.000 claims abstract description 370
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 105
- -1 p-methoxybenzyl Chemical group 0.000 claims description 98
- 229910052739 hydrogen Inorganic materials 0.000 claims description 82
- 239000001257 hydrogen Substances 0.000 claims description 82
- 125000000623 heterocyclic group Chemical group 0.000 claims description 64
- 239000000203 mixture Substances 0.000 claims description 62
- 125000002947 alkylene group Chemical group 0.000 claims description 58
- 125000003118 aryl group Chemical group 0.000 claims description 57
- 125000001072 heteroaryl group Chemical group 0.000 claims description 52
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 51
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 50
- 125000003342 alkenyl group Chemical group 0.000 claims description 49
- 125000000304 alkynyl group Chemical group 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 45
- 125000000732 arylene group Chemical group 0.000 claims description 37
- 229910052736 halogen Inorganic materials 0.000 claims description 37
- 150000002367 halogens Chemical group 0.000 claims description 37
- 125000004450 alkenylene group Chemical group 0.000 claims description 36
- 125000005549 heteroarylene group Chemical group 0.000 claims description 36
- 125000004419 alkynylene group Chemical group 0.000 claims description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
- 238000010438 heat treatment Methods 0.000 claims description 31
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 30
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 claims description 30
- 125000001188 haloalkyl group Chemical group 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 239000003153 chemical reaction reagent Substances 0.000 claims description 23
- PAPNRQCYSFBWDI-UHFFFAOYSA-N 2,5-Dimethyl-1H-pyrrole Chemical compound CC1=CC=C(C)N1 PAPNRQCYSFBWDI-UHFFFAOYSA-N 0.000 claims description 22
- 239000003054 catalyst Substances 0.000 claims description 22
- 239000012458 free base Substances 0.000 claims description 22
- 229910052763 palladium Inorganic materials 0.000 claims description 21
- 239000002585 base Substances 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 125000003282 alkyl amino group Chemical group 0.000 claims description 15
- 125000005529 alkyleneoxy group Chemical group 0.000 claims description 15
- 125000005532 aryl alkyleneoxy group Chemical group 0.000 claims description 15
- 125000004104 aryloxy group Chemical group 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 15
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 15
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 15
- 125000004043 oxo group Chemical group O=* 0.000 claims description 15
- 230000002378 acidificating effect Effects 0.000 claims description 14
- 150000002148 esters Chemical class 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 238000003776 cleavage reaction Methods 0.000 claims description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
- 230000007017 scission Effects 0.000 claims description 10
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 9
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 9
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 150000001408 amides Chemical class 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
- 150000003512 tertiary amines Chemical class 0.000 claims description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
- 239000011630 iodine Substances 0.000 claims description 7
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
- GRNOZCCBOFGDCL-UHFFFAOYSA-N 2,2,2-trichloroacetyl isocyanate Chemical compound ClC(Cl)(Cl)C(=O)N=C=O GRNOZCCBOFGDCL-UHFFFAOYSA-N 0.000 claims description 5
- 230000001590 oxidative effect Effects 0.000 claims description 5
- 229910052759 nickel Inorganic materials 0.000 claims description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- NZZFYRREKKOMAT-OUBTZVSYSA-N diiodomethane Chemical group I[13CH2]I NZZFYRREKKOMAT-OUBTZVSYSA-N 0.000 claims description 2
- 230000002519 immonomodulatory effect Effects 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 18
- 238000002360 preparation method Methods 0.000 abstract description 34
- 238000006243 chemical reaction Methods 0.000 description 209
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- 239000000243 solution Substances 0.000 description 77
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 69
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 68
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 56
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
- 239000002904 solvent Substances 0.000 description 47
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 40
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 33
- 239000007787 solid Substances 0.000 description 30
- 238000010992 reflux Methods 0.000 description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
- 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 24
- 229910052757 nitrogen Inorganic materials 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- 229910000029 sodium carbonate Inorganic materials 0.000 description 20
- 235000017550 sodium carbonate Nutrition 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- 238000005859 coupling reaction Methods 0.000 description 18
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 16
- 239000010410 layer Substances 0.000 description 16
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 16
- 238000001914 filtration Methods 0.000 description 15
- 239000012299 nitrogen atmosphere Substances 0.000 description 15
- 239000012267 brine Substances 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- JAFMOTJMRSZOJE-UHFFFAOYSA-N 1,1,1-trimethoxybutane Chemical compound CCCC(OC)(OC)OC JAFMOTJMRSZOJE-UHFFFAOYSA-N 0.000 description 11
- 125000001309 chloro group Chemical group Cl* 0.000 description 11
- 238000004440 column chromatography Methods 0.000 description 11
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 11
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 238000007363 ring formation reaction Methods 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 10
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 230000003197 catalytic effect Effects 0.000 description 10
- 238000007796 conventional method Methods 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 238000006069 Suzuki reaction reaction Methods 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 125000004122 cyclic group Chemical group 0.000 description 9
- 150000002460 imidazoles Chemical class 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- FGWYWKIOMUZSQF-UHFFFAOYSA-N 1,1,1-triethoxypropane Chemical compound CCOC(CC)(OCC)OCC FGWYWKIOMUZSQF-UHFFFAOYSA-N 0.000 description 8
- MEUWQVWJLLBVQI-UHFFFAOYSA-N 2-aminopropanedinitrile;4-methylbenzenesulfonic acid Chemical compound N#CC([NH3+])C#N.CC1=CC=C(S([O-])(=O)=O)C=C1 MEUWQVWJLLBVQI-UHFFFAOYSA-N 0.000 description 8
- 125000000524 functional group Chemical group 0.000 description 8
- 230000009466 transformation Effects 0.000 description 8
- 238000010168 coupling process Methods 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 235000011181 potassium carbonates Nutrition 0.000 description 7
- 150000003141 primary amines Chemical class 0.000 description 7
- 235000011121 sodium hydroxide Nutrition 0.000 description 7
- RTRBFWFMOFEZNI-UHFFFAOYSA-N 5-amino-1-(2-methylpropyl)-2-propylimidazole-4-carbonitrile Chemical compound CCCC1=NC(C#N)=C(N)N1CC(C)C RTRBFWFMOFEZNI-UHFFFAOYSA-N 0.000 description 6
- JPKLQPDMNMFWBV-UHFFFAOYSA-N 5-iodo-1-(2-methylpropyl)-2-propylimidazole-4-carbonitrile Chemical compound CCCC1=NC(C#N)=C(I)N1CC(C)C JPKLQPDMNMFWBV-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 6
- 239000012346 acetyl chloride Substances 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- 230000008878 coupling Effects 0.000 description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 238000010189 synthetic method Methods 0.000 description 6
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 6
- UWTNNCFLQICMEL-UHFFFAOYSA-N (4-aminopyridin-3-yl)boronic acid;hydrochloride Chemical compound Cl.NC1=CC=NC=C1B(O)O UWTNNCFLQICMEL-UHFFFAOYSA-N 0.000 description 5
- XUXVVQKJULMMKX-UHFFFAOYSA-N 1,1,1-trimethoxypentane Chemical compound CCCCC(OC)(OC)OC XUXVVQKJULMMKX-UHFFFAOYSA-N 0.000 description 5
- GXDKXRIMUVUELI-UHFFFAOYSA-N 2-aminopropanedinitrile Chemical compound N#CC(N)C#N GXDKXRIMUVUELI-UHFFFAOYSA-N 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 5
- 238000005576 amination reaction Methods 0.000 description 5
- 239000000908 ammonium hydroxide Substances 0.000 description 5
- 150000008064 anhydrides Chemical class 0.000 description 5
- 150000001502 aryl halides Chemical class 0.000 description 5
- 229950005228 bromoform Drugs 0.000 description 5
- 238000006880 cross-coupling reaction Methods 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 239000012948 isocyanate Substances 0.000 description 5
- 150000002513 isocyanates Chemical class 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- DIRRKLFMHQUJCM-UHFFFAOYSA-N (2-aminophenyl)boronic acid Chemical compound NC1=CC=CC=C1B(O)O DIRRKLFMHQUJCM-UHFFFAOYSA-N 0.000 description 4
- WPDASZCYRKGSTO-UHFFFAOYSA-N (2-aminophenyl)boronic acid;hydrochloride Chemical compound Cl.NC1=CC=CC=C1B(O)O WPDASZCYRKGSTO-UHFFFAOYSA-N 0.000 description 4
- HDPNBNXLBDFELL-UHFFFAOYSA-N 1,1,1-trimethoxyethane Chemical compound COC(C)(OC)OC HDPNBNXLBDFELL-UHFFFAOYSA-N 0.000 description 4
- HQBUPOAKJGJGCD-UHFFFAOYSA-N 3h-imidazo[4,5-c]quinolin-4-amine Chemical compound NC1=NC2=CC=CC=C2C2=C1N=CN2 HQBUPOAKJGJGCD-UHFFFAOYSA-N 0.000 description 4
- PQZJEUBVQJDPRM-UHFFFAOYSA-N 5-(2-aminophenyl)-2-butyl-1-(2-methylpropyl)imidazole-4-carbonitrile Chemical compound CC(C)CN1C(CCCC)=NC(C#N)=C1C1=CC=CC=C1N PQZJEUBVQJDPRM-UHFFFAOYSA-N 0.000 description 4
- LDQRGBWVOAXSDD-UHFFFAOYSA-N 5-bromo-1,2-dimethylimidazole-4-carbonitrile Chemical compound CC1=NC(C#N)=C(Br)N1C LDQRGBWVOAXSDD-UHFFFAOYSA-N 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 150000001204 N-oxides Chemical class 0.000 description 4
- 235000019502 Orange oil Nutrition 0.000 description 4
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 238000006619 Stille reaction Methods 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- HNQIVZYLYMDVSB-NJFSPNSNSA-N methanesulfonamide Chemical compound [14CH3]S(N)(=O)=O HNQIVZYLYMDVSB-NJFSPNSNSA-N 0.000 description 4
- 239000010502 orange oil Substances 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 239000011877 solvent mixture Substances 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
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- DNJUJYLXGOWPIY-UHFFFAOYSA-N tert-butyl n-[2-[2-(4-cyano-5-iodo-2-propylimidazol-1-yl)ethoxy]ethyl]carbamate Chemical compound CCCC1=NC(C#N)=C(I)N1CCOCCNC(=O)OC(C)(C)C DNJUJYLXGOWPIY-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
Classifications
-
- 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
-
- 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
- C07D233/66—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US66784005P | 2005-04-01 | 2005-04-01 | |
| US60/667,840 | 2005-04-01 | ||
| PCT/US2006/012022 WO2006121528A2 (en) | 2005-04-01 | 2006-03-31 | Ring closing and related methods and intermediates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2602853A1 true CA2602853A1 (en) | 2006-11-16 |
Family
ID=37397032
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002602853A Abandoned CA2602853A1 (en) | 2005-04-01 | 2006-03-31 | Ring closing and related methods and intermediates |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US8168802B2 (https=) |
| EP (1) | EP1863770A4 (https=) |
| JP (1) | JP2008535831A (https=) |
| AU (1) | AU2006244635A1 (https=) |
| CA (1) | CA2602853A1 (https=) |
| WO (1) | WO2006121528A2 (https=) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040265351A1 (en) | 2003-04-10 | 2004-12-30 | Miller Richard L. | Methods and compositions for enhancing immune response |
| BRPI0413558A (pt) | 2003-08-12 | 2006-10-17 | 3M Innovative Properties Co | compostos contendo imidazo substituìdo por hidroxilamina |
| AU2004268625B2 (en) | 2003-08-27 | 2011-03-31 | 3M Innovative Properties Company | Aryloxy and arylalkyleneoxy substituted imidazoquinolines |
| AU2004270201A1 (en) | 2003-09-05 | 2005-03-17 | 3M Innovative Properties Company | Treatment for CD5+ B cell lymphoma |
| KR20060120069A (ko) | 2003-10-03 | 2006-11-24 | 쓰리엠 이노베이티브 프로퍼티즈 컴파니 | 피라졸로피리딘 및 그의 유사체 |
| AR046046A1 (es) | 2003-10-03 | 2005-11-23 | 3M Innovative Properties Co | Imidazoquinolinas alcoxi sustituidas. composiciones farmaceuticas. |
| US7544697B2 (en) | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
| EP1685129A4 (en) | 2003-11-14 | 2008-10-22 | 3M Innovative Properties Co | OXIMSUBSTITUTED IMIDAZORING CONNECTIONS |
| CA2545825A1 (en) | 2003-11-14 | 2005-06-02 | 3M Innovative Properties Company | Hydroxylamine substituted imidazo ring compounds |
| CA2547020C (en) | 2003-11-25 | 2014-03-25 | 3M Innovative Properties Company | 1h-imidazo[4,5-c]pyridine-4-amine derivatives as immune response modifier |
| JP2007517035A (ja) | 2003-12-29 | 2007-06-28 | スリーエム イノベイティブ プロパティズ カンパニー | アリールアルケニルおよびアリールアルキニル置換されたイミダゾキノリン |
| EP1699788A2 (en) | 2003-12-30 | 2006-09-13 | 3M Innovative Properties Company | Imidazoquinolinyl, imidazopyridinyl and imidazonaphthyridinyl sulfonamides |
| WO2006065280A2 (en) | 2004-06-18 | 2006-06-22 | 3M Innovative Properties Company | Isoxazole, dihydroisoxazole, and oxadiazole substituted imidazo ring compounds and methods |
| US8541438B2 (en) | 2004-06-18 | 2013-09-24 | 3M Innovative Properties Company | Substituted imidazoquinolines, imidazopyridines, and imidazonaphthyridines |
| EP1789042B1 (en) | 2004-09-02 | 2012-05-02 | 3M Innovative Properties Company | 1-alkoxy 1h-imidazo ring systems and methods |
| JP5543068B2 (ja) | 2004-12-30 | 2014-07-09 | スリーエム イノベイティブ プロパティズ カンパニー | キラル縮合［１，２］イミダゾ［４，５−ｃ］環状化合物 |
| EP1831221B1 (en) | 2004-12-30 | 2012-08-08 | 3M Innovative Properties Company | Substituted chiral fused 1,2 imidazo 4,5-c ring compounds |
| AU2006210392A1 (en) | 2005-02-04 | 2006-08-10 | Coley Pharmaceutical Group, Inc. | Aqueous gel formulations containing immune response modifiers |
| AU2006212765B2 (en) | 2005-02-09 | 2012-02-02 | 3M Innovative Properties Company | Alkyloxy substituted thiazoloquinolines and thiazolonaphthyridines |
| AU2006213746A1 (en) | 2005-02-11 | 2006-08-17 | Coley Pharmaceutical Group, Inc. | Oxime and hydroxylamine substituted imidazo(4,5-c) ring compounds and methods |
| AU2006216686A1 (en) | 2005-02-23 | 2006-08-31 | Coley Pharmaceutical Group, Inc. | Method of preferentially inducing the biosynthesis of interferon |
| EP1869043A2 (en) | 2005-04-01 | 2007-12-26 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridine-1,4-diamines and analogs thereof |
| AU2006232375A1 (en) | 2005-04-01 | 2006-10-12 | Coley Pharmaceutical Group, Inc. | 1-substituted pyrazolo (3,4-c) ring compounds as modulators of cytokine biosynthesis for the treatment of viral infections and neoplastic diseases |
| KR20080083270A (ko) * | 2005-11-04 | 2008-09-17 | 콜레이 파마시티컬 그룹, 인코포레이티드 | 하이드록시 및 알콕시 치환된 1에이치 이미다조퀴놀린 및방법 |
| EP1988896A4 (en) | 2006-02-22 | 2011-07-27 | 3M Innovative Properties Co | CONJUGATES TO MODIFY IMMUNE REACTIONS |
| US7906506B2 (en) | 2006-07-12 | 2011-03-15 | 3M Innovative Properties Company | Substituted chiral fused [1,2] imidazo [4,5-c] ring compounds and methods |
| US20080149123A1 (en) | 2006-12-22 | 2008-06-26 | Mckay William D | Particulate material dispensing hairbrush with combination bristles |
| US9242980B2 (en) | 2010-08-17 | 2016-01-26 | 3M Innovative Properties Company | Lipidated immune response modifier compound compositions, formulations, and methods |
| JP6460789B2 (ja) | 2011-06-03 | 2019-01-30 | スリーエム イノベイティブ プロパティズ カンパニー | ポリエチレングリコールセグメントを有するヘテロ２官能性リンカー及び該リンカーから調製された免疫反応調節複合体 |
| BR112013031039B1 (pt) | 2011-06-03 | 2020-04-28 | 3M Innovative Properties Co | compostos de hidrazino 1h-imidazoquinolina-4-aminas, conjugados feitos destes compostos, composição e composição farmacêutica compreendendo ditos compostos e conjugados, usos dos mesmos e método de fabricação do conjugado |
| JP5935123B2 (ja) * | 2011-08-22 | 2016-06-15 | 国立研究開発法人産業技術総合研究所 | 高温高圧クロスカップリング法 |
| ES2538880B1 (es) * | 2013-12-24 | 2016-09-08 | Laboratorios Viñas S.A. | Un procedimiento para obtener 4-amino-1-isobutil-1H-imidazo[4,5-c]quinoleína |
| KR102685007B1 (ko) * | 2015-08-31 | 2024-07-12 | 쓰리엠 이노베이티브 프로퍼티즈 컴파니 | 구아니딘 치환된 이미다조[4,5-c] 고리 화합물 |
| US10118925B2 (en) | 2015-08-31 | 2018-11-06 | 3M Innovative Properties Company | Imidazo[4,5-c] ring compounds containing substituted guanidine groups |
| RU2722149C1 (ru) * | 2015-09-14 | 2020-05-27 | Пфайзер Инк. | Новые производные имидазо[4,5-c] хинолинов и имидазо[4,5-c][1,5] нафтиридинов в качестве ингибиторов LRRK2 |
| US10766896B2 (en) | 2017-03-01 | 2020-09-08 | 3M Innovative Properties Company | Imidazo[4,5-c] ring compounds containing guanidine substituted benzamide groups |
| WO2019123178A1 (en) | 2017-12-20 | 2019-06-27 | 3M Innovative Properties Company | Amide substitued imidazo[4,5-c]quinoline compounds with a branched chain linking group for use as an immune response modifier |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1645976A1 (de) | 1966-06-18 | 1971-01-21 | Ajinomoto Kk | Verfahren zur Herstellung von Adenosin und 2',3'-O-Isopropylidenadenosin |
| US4420617A (en) * | 1980-03-28 | 1983-12-13 | Sterling Drug Inc. | 5(Pyridinyl)pyridin-2-amines |
| DE3723070A1 (de) * | 1987-07-11 | 1989-01-19 | Bayer Ag | Verfahren zur herstellung von substituierten pyridylalkylketonen |
| CA2131680C (en) | 1993-09-17 | 2006-11-07 | Gerhard Stucky | Process for preparing imidazopyridine derivatives |
| UA67760C2 (uk) * | 1997-12-11 | 2004-07-15 | Міннесота Майнінг Енд Мануфакчурінг Компані | Імідазонафтиридин та тетрагідроімідазонафтиридин, фармацевтична композиція, спосіб індукування біосинтезу цитокінів та спосіб лікування вірусної інфекції, проміжні сполуки |
| AU2220801A (en) * | 1999-12-22 | 2001-07-03 | Kyorin Pharmaceutical Co. Ltd. | Tricyclic compounds and addition salts thereof |
| CA2399136A1 (en) | 2000-02-09 | 2001-08-16 | Hideo Kato | 1h-imidazopyridine derivatives |
| US6677349B1 (en) | 2001-12-21 | 2004-01-13 | 3M Innovative Properties Company | Sulfonamide and sulfamide substituted imidazoquinolines |
| US7544697B2 (en) * | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
-
2006
- 2006-03-31 JP JP2008504436A patent/JP2008535831A/ja active Pending
- 2006-03-31 AU AU2006244635A patent/AU2006244635A1/en not_active Abandoned
- 2006-03-31 WO PCT/US2006/012022 patent/WO2006121528A2/en not_active Ceased
- 2006-03-31 CA CA002602853A patent/CA2602853A1/en not_active Abandoned
- 2006-03-31 EP EP06769789A patent/EP1863770A4/en not_active Withdrawn
- 2006-03-31 US US11/887,525 patent/US8168802B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU2006244635A1 (en) | 2006-11-16 |
| EP1863770A4 (en) | 2010-05-05 |
| EP1863770A2 (en) | 2007-12-12 |
| JP2008535831A (ja) | 2008-09-04 |
| US8168802B2 (en) | 2012-05-01 |
| US20110269965A1 (en) | 2011-11-03 |
| WO2006121528A3 (en) | 2007-09-13 |
| WO2006121528A2 (en) | 2006-11-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20131227 |