NZ537390A - 5-(1,3-oxazol-2-yl) benzoic acid derivatives useful in the preparation of compounds and pharmaceutical compositions useful for treating Alzheimer?s disease and related conditions - Google Patents
5-(1,3-oxazol-2-yl) benzoic acid derivatives useful in the preparation of compounds and pharmaceutical compositions useful for treating Alzheimer?s disease and related conditionsInfo
- Publication number
- NZ537390A NZ537390A NZ537390A NZ53739003A NZ537390A NZ 537390 A NZ537390 A NZ 537390A NZ 537390 A NZ537390 A NZ 537390A NZ 53739003 A NZ53739003 A NZ 53739003A NZ 537390 A NZ537390 A NZ 537390A
- Authority
- NZ
- New Zealand
- Prior art keywords
- alkyl
- optionally substituted
- heteroaryl
- aryl
- groups
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 117
- 238000002360 preparation method Methods 0.000 title abstract description 18
- IMAITKPPSLYKDS-UHFFFAOYSA-N 3-(1,3-oxazol-2-yl)benzoic acid Chemical class OC(=O)C1=CC=CC(C=2OC=CN=2)=C1 IMAITKPPSLYKDS-UHFFFAOYSA-N 0.000 title description 2
- 239000008194 pharmaceutical composition Substances 0.000 title description 2
- 201000010099 disease Diseases 0.000 title 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 58
- 239000011541 reaction mixture Substances 0.000 claims abstract description 33
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 32
- 239000003054 catalyst Substances 0.000 claims abstract description 30
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 23
- 239000002904 solvent Substances 0.000 claims abstract description 20
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 8
- 125000005605 benzo group Chemical group 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 5
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 142
- -1 3-ethynylphenyl Chemical group 0.000 claims description 79
- 125000003545 alkoxy group Chemical group 0.000 claims description 44
- 229910052736 halogen Inorganic materials 0.000 claims description 41
- 150000002367 halogens Chemical class 0.000 claims description 41
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 39
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
- 239000000203 mixture Substances 0.000 claims description 31
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 125000000304 alkynyl group Chemical group 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 13
- 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 13
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 11
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 10
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [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 claims description 10
- 229910002666 PdCl2 Inorganic materials 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 9
- 239000008346 aqueous phase Substances 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 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 8
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 8
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 7
- 239000000654 additive Substances 0.000 claims description 7
- 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 claims description 7
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
- 229910052723 transition metal Inorganic materials 0.000 claims description 7
- 150000003624 transition metals Chemical group 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-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
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 6
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 6
- 239000000284 extract Substances 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 230000014759 maintenance of location Effects 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 150000001721 carbon Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 4
- CDLDJGNSVFBIAG-UHFFFAOYSA-N 2,2,3,3-tetramethyloxolane Chemical compound CC1(C)CCOC1(C)C CDLDJGNSVFBIAG-UHFFFAOYSA-N 0.000 claims description 3
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims description 3
- 239000000010 aprotic solvent Substances 0.000 claims description 3
- 239000012043 crude product Substances 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 238000010898 silica gel chromatography Methods 0.000 claims description 3
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims description 2
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- BTANRVKWQNVYAZ-UHFFFAOYSA-N Sec-butyl alcohol Natural products CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 21
- 239000007787 solid Substances 0.000 description 19
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- 125000003282 alkyl amino group Chemical group 0.000 description 16
- 239000002253 acid Substances 0.000 description 14
- 235000005074 zinc chloride Nutrition 0.000 description 14
- 239000011592 zinc chloride Substances 0.000 description 14
- 235000019439 ethyl acetate Nutrition 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 11
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- FNXLCIKXHOPCKH-UHFFFAOYSA-N bromamine Chemical compound BrN FNXLCIKXHOPCKH-UHFFFAOYSA-N 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 238000005859 coupling reaction Methods 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000008065 acid anhydrides Chemical class 0.000 description 6
- 230000008878 coupling Effects 0.000 description 6
- 238000010168 coupling process Methods 0.000 description 6
- 125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
- 230000000996 additive effect Effects 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 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 5
- 125000002883 imidazolyl group Chemical group 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 125000005036 alkoxyphenyl group Chemical group 0.000 description 4
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 125000001188 haloalkyl group Chemical group 0.000 description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- 150000003751 zinc Chemical class 0.000 description 3
- NPIWIXRTEOIQKT-VQTJNVASSA-N (2r,3s)-3-amino-4-(3,5-difluorophenyl)-1-[[1-(3-ethynylphenyl)cyclopropyl]amino]butan-2-ol Chemical compound C([C@H](N)[C@H](O)CNC1(CC1)C=1C=C(C=CC=1)C#C)C1=CC(F)=CC(F)=C1 NPIWIXRTEOIQKT-VQTJNVASSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- FMUDGJVWDRNMMF-JHOUSYSJSA-N 1-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-5-(1,3-oxazol-2-yl)-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound C=1C(C(=O)N(CCC)CCC)=CC(C(=O)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@H](O)CNCC=2C=C(CC)C=CC=2)=CC=1C1=NC=CO1 FMUDGJVWDRNMMF-JHOUSYSJSA-N 0.000 description 2
- RKHACGKSFLURLC-SZAHLOSFSA-N 1-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[[1-(3-ethynylphenyl)cyclopropyl]amino]-3-hydroxybutan-2-yl]-5-(1,3-oxazol-2-yl)-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound C=1C(C(=O)N(CCC)CCC)=CC(C(=O)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@H](O)CNC2(CC2)C=2C=C(C=CC=2)C#C)=CC=1C1=NC=CO1 RKHACGKSFLURLC-SZAHLOSFSA-N 0.000 description 2
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- ZJSQZQMVXKZAGW-UHFFFAOYSA-N 2H-benzotriazol-4-ol hydrate Chemical compound O.OC1=CC=CC2=C1N=NN2 ZJSQZQMVXKZAGW-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 229910014585 C2-Ce Inorganic materials 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 125000005037 alkyl phenyl group Chemical group 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 description 2
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 2
- 239000012964 benzotriazole Substances 0.000 description 2
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
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- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- ZNZXRHRWBUGBIB-UHFFFAOYSA-L zinc;1,3-oxazole;dichloride Chemical compound [Cl-].[Cl-].[Zn+2].C1=COC=N1 ZNZXRHRWBUGBIB-UHFFFAOYSA-L 0.000 description 1
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US39028502P | 2002-06-20 | 2002-06-20 | |
| US45047803P | 2003-02-27 | 2003-02-27 | |
| PCT/US2003/019585 WO2004000821A1 (en) | 2002-06-20 | 2003-06-20 | Process for preparing 5-(1, 3-oxazol-2-yl) benzoic acid derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ537390A true NZ537390A (en) | 2006-07-28 |
Family
ID=30003150
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ537390A NZ537390A (en) | 2002-06-20 | 2003-06-20 | 5-(1,3-oxazol-2-yl) benzoic acid derivatives useful in the preparation of compounds and pharmaceutical compositions useful for treating Alzheimer?s disease and related conditions |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US7115747B2 (enExample) |
| EP (1) | EP1532123B1 (enExample) |
| JP (1) | JP2005533811A (enExample) |
| CN (1) | CN1324017C (enExample) |
| AT (1) | ATE370131T1 (enExample) |
| AU (1) | AU2003249344A1 (enExample) |
| BR (1) | BR0312439A (enExample) |
| CA (1) | CA2489988A1 (enExample) |
| CO (1) | CO5670350A2 (enExample) |
| DE (1) | DE60315664D1 (enExample) |
| EA (1) | EA008389B1 (enExample) |
| IL (1) | IL165763A0 (enExample) |
| MX (1) | MXPA04012630A (enExample) |
| NO (1) | NO20045497L (enExample) |
| NZ (1) | NZ537390A (enExample) |
| PL (1) | PL374999A1 (enExample) |
| WO (1) | WO2004000821A1 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR0316629A (pt) * | 2002-11-27 | 2005-10-11 | Elan Pharm Inc | Uréias e carbamatos substituìdos |
| TW200738701A (en) * | 2005-07-26 | 2007-10-16 | Du Pont | Fungicidal carboxamides |
| US7872009B2 (en) * | 2005-11-21 | 2011-01-18 | Amgen Inc. | Beta-Secretase modulators and methods of use |
| US7838676B2 (en) * | 2005-11-21 | 2010-11-23 | Amgen Inc. | Beta-secretase modulators and methods of use |
| US7745484B2 (en) | 2005-11-21 | 2010-06-29 | Amgen Inc. | Beta-secretase modulators and methods of use |
| EP1971598A1 (en) | 2005-11-21 | 2008-09-24 | Amgen Inc. | Beta-secretase modulators and methods of use |
| WO2008137954A2 (en) * | 2007-05-07 | 2008-11-13 | Environmental Packaging Technologies Limited | Universal shipping container |
| US8163909B2 (en) | 2007-05-25 | 2012-04-24 | Amgen Inc. | Substituted hydroxyethyl amine compounds as beta-secretase modulators and methods of use |
| JP5440984B2 (ja) * | 2007-05-25 | 2014-03-12 | アムジエン・インコーポレーテツド | β−セクレターゼ修飾剤としての置換ヒドロキシエチルアミン化合物および使用方法 |
| US7803809B2 (en) | 2008-11-12 | 2010-09-28 | Amgen Inc. | Substituted pyrano [2,3-b] pyridinamine compounds as beta-secretase modulators and methods of use |
| KR20110073511A (ko) | 2008-09-11 | 2011-06-29 | 암젠 인크 | 베타세크레타제 조절제로서의 스피로-테트라사이클릭 고리 화합물 및 사용 방법 |
| WO2011063233A1 (en) | 2009-11-23 | 2011-05-26 | Amgen Inc. | Amino heteroaryl compounds as beta-secretase modulators and methods of use |
| EP2504330A1 (en) | 2009-11-23 | 2012-10-03 | Amgen Inc. | Amino heteroaryl compounds as beta-secretase modulators and methods of use |
| CA2788363A1 (en) | 2010-01-19 | 2011-07-28 | Amgen Inc. | Amino heteroaryl compounds as beta-secretase modulators and methods of use |
| JP5584352B2 (ja) | 2010-03-15 | 2014-09-03 | アムジエン・インコーポレーテツド | β−セクレターゼ調節剤としてのアミノ−ジヒドロオキサジン系およびアミノ−ジヒドロチアジン系スピロ化合物ならびにそれらの医学的用途 |
| CA2791281A1 (en) | 2010-03-15 | 2011-09-22 | Amgen Inc. | Spiro-tetracyclic ring compounds as beta-secretase modulators |
| EP2673279A1 (en) | 2011-02-07 | 2013-12-18 | Amgen Inc. | 5-amino-oxazepine and 5-amino-thiazepane compounds as beta-secretase antagonists and methods of use |
| EP2758406A1 (en) | 2011-09-21 | 2014-07-30 | Amgen Inc. | Amino-oxazines and amino-dihydrothiazine compounds as beta-secretase modulators and methods of use |
| US9725469B2 (en) | 2012-11-15 | 2017-08-08 | Amgen, Inc. | Amino-oxazine and amino-dihydrothiazine compounds as beta-secretase modulators and methods of use |
| US11272751B2 (en) | 2016-03-01 | 2022-03-15 | Nicholas Popejoy | Protective headgear, impact diffusing systems and methods |
| US9462841B1 (en) | 2016-03-01 | 2016-10-11 | William Popejoy | Protective headgear and shoulder pad apparatus and methods |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PE20020276A1 (es) * | 2000-06-30 | 2002-04-06 | Elan Pharm Inc | COMPUESTOS DE AMINA SUSTITUIDA COMO INHIBIDORES DE ß-SECRETASA PARA EL TRATAMIENTO DE ALZHEIMER |
| CA2462851A1 (en) | 2001-10-04 | 2003-04-10 | Elan Pharmaceuticals, Inc. | Hydroxypropylamines |
| AR039555A1 (es) * | 2001-11-08 | 2005-02-23 | Upjohn Co | Derivados n,n'-sustituidos de 1,3-diamino-2-hidroxipropano |
| GB0325830D0 (en) * | 2003-11-05 | 2003-12-10 | Novartis Ag | Organic compounds |
-
2003
- 2003-06-20 CN CNB038144476A patent/CN1324017C/zh not_active Expired - Fee Related
- 2003-06-20 MX MXPA04012630A patent/MXPA04012630A/es active IP Right Grant
- 2003-06-20 NZ NZ537390A patent/NZ537390A/en unknown
- 2003-06-20 PL PL03374999A patent/PL374999A1/xx unknown
- 2003-06-20 CA CA002489988A patent/CA2489988A1/en not_active Abandoned
- 2003-06-20 JP JP2004516055A patent/JP2005533811A/ja active Pending
- 2003-06-20 DE DE60315664T patent/DE60315664D1/de not_active Expired - Lifetime
- 2003-06-20 AU AU2003249344A patent/AU2003249344A1/en not_active Abandoned
- 2003-06-20 EA EA200401510A patent/EA008389B1/ru unknown
- 2003-06-20 AT AT03761206T patent/ATE370131T1/de not_active IP Right Cessation
- 2003-06-20 US US10/600,100 patent/US7115747B2/en not_active Expired - Fee Related
- 2003-06-20 EP EP03761206A patent/EP1532123B1/en not_active Expired - Lifetime
- 2003-06-20 WO PCT/US2003/019585 patent/WO2004000821A1/en not_active Ceased
- 2003-06-20 BR BR0312439-8A patent/BR0312439A/pt not_active IP Right Cessation
-
2004
- 2004-12-14 IL IL16576304A patent/IL165763A0/xx unknown
- 2004-12-16 NO NO20045497A patent/NO20045497L/no not_active Application Discontinuation
-
2005
- 2005-01-20 CO CO05004558A patent/CO5670350A2/es not_active Application Discontinuation
-
2006
- 2006-10-03 US US11/538,155 patent/US20070105921A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| DE60315664D1 (de) | 2007-09-27 |
| CN1324017C (zh) | 2007-07-04 |
| EP1532123A1 (en) | 2005-05-25 |
| NO20045497D0 (no) | 2004-12-16 |
| NO20045497L (no) | 2005-03-07 |
| PL374999A1 (en) | 2005-11-14 |
| EA008389B1 (ru) | 2007-04-27 |
| CN1662510A (zh) | 2005-08-31 |
| MXPA04012630A (es) | 2005-09-30 |
| BR0312439A (pt) | 2005-05-10 |
| EP1532123B1 (en) | 2007-08-15 |
| AU2003249344A1 (en) | 2004-01-06 |
| US20070105921A1 (en) | 2007-05-10 |
| JP2005533811A (ja) | 2005-11-10 |
| CO5670350A2 (es) | 2006-08-31 |
| CA2489988A1 (en) | 2003-12-31 |
| HK1081543A1 (zh) | 2006-05-19 |
| IL165763A0 (en) | 2006-01-15 |
| ATE370131T1 (de) | 2007-09-15 |
| US7115747B2 (en) | 2006-10-03 |
| EA200401510A1 (ru) | 2005-06-30 |
| WO2004000821A1 (en) | 2003-12-31 |
| US20040063965A1 (en) | 2004-04-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) |