CN1203089C - 新化合物 - Google Patents
新化合物 Download PDFInfo
- Publication number
- CN1203089C CN1203089C CNB95196643XA CN95196643A CN1203089C CN 1203089 C CN1203089 C CN 1203089C CN B95196643X A CNB95196643X A CN B95196643XA CN 95196643 A CN95196643 A CN 95196643A CN 1203089 C CN1203089 C CN 1203089C
- Authority
- CN
- China
- Prior art keywords
- phenyl
- preparation example
- nmr
- apci
- mass
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 151
- 150000003839 salts Chemical class 0.000 claims abstract description 74
- 229920001184 polypeptide Polymers 0.000 claims abstract description 23
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 23
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 238000011282 treatment Methods 0.000 claims abstract description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 270
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 166
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 59
- 125000004193 piperazinyl group Chemical group 0.000 claims description 9
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 150000008065 acid anhydrides Chemical class 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 3
- 150000001266 acyl halides Chemical class 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 430
- 230000000845 anti-microbial effect Effects 0.000 abstract description 7
- 241001465754 Metazoa Species 0.000 abstract description 3
- 208000005384 Pneumocystis Pneumonia Diseases 0.000 abstract description 3
- 206010073755 Pneumocystis jirovecii pneumonia Diseases 0.000 abstract description 3
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 229920002498 Beta-glucan Polymers 0.000 abstract 1
- 208000035473 Communicable disease Diseases 0.000 abstract 1
- 206010035660 Pneumocystis Infections Diseases 0.000 abstract 1
- 206010073756 Pneumocystis jirovecii infection Diseases 0.000 abstract 1
- 230000000843 anti-fungal effect Effects 0.000 abstract 1
- 201000000317 pneumocystosis Diseases 0.000 abstract 1
- 230000000069 prophylactic effect Effects 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- -1 heterocyclic radical Chemical class 0.000 description 367
- 125000003118 aryl group Chemical group 0.000 description 224
- 239000002585 base Substances 0.000 description 208
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 177
- 125000000217 alkyl group Chemical group 0.000 description 137
- 238000004458 analytical method Methods 0.000 description 120
- 239000011734 sodium Substances 0.000 description 115
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 114
- 239000000203 mixture Substances 0.000 description 106
- 125000001424 substituent group Chemical group 0.000 description 105
- 239000001301 oxygen Substances 0.000 description 94
- 229910052760 oxygen Inorganic materials 0.000 description 94
- 239000000243 solution Substances 0.000 description 94
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 90
- 125000003435 aroyl group Chemical group 0.000 description 83
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 78
- 150000001335 aliphatic alkanes Chemical class 0.000 description 68
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 58
- 125000000623 heterocyclic group Chemical group 0.000 description 57
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 57
- 230000002829 reductive effect Effects 0.000 description 56
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 125000004433 nitrogen atom Chemical group N* 0.000 description 51
- 239000012044 organic layer Substances 0.000 description 51
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 50
- 239000011541 reaction mixture Substances 0.000 description 49
- 238000001914 filtration Methods 0.000 description 47
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 46
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 46
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 45
- 239000000706 filtrate Substances 0.000 description 38
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 34
- 238000005406 washing Methods 0.000 description 33
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 32
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 32
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- 238000001035 drying Methods 0.000 description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000000725 suspension Substances 0.000 description 27
- 125000001624 naphthyl group Chemical group 0.000 description 26
- 229940095102 methyl benzoate Drugs 0.000 description 25
- 125000005447 octyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 24
- 238000001556 precipitation Methods 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 23
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 22
- 239000002904 solvent Substances 0.000 description 22
- 238000009834 vaporization Methods 0.000 description 21
- 230000008016 vaporization Effects 0.000 description 20
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 19
- 229920006395 saturated elastomer Polymers 0.000 description 19
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 description 18
- 230000006837 decompression Effects 0.000 description 17
- 239000002253 acid Substances 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 14
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 14
- 239000003826 tablet Substances 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 12
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 12
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 12
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 238000001704 evaporation Methods 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 125000001425 triazolyl group Chemical group 0.000 description 11
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 10
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 10
- 238000003810 ethyl acetate extraction Methods 0.000 description 10
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 9
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 9
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 9
- 125000004104 aryloxy group Chemical group 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 229960004756 ethanol Drugs 0.000 description 9
- 150000004702 methyl esters Chemical class 0.000 description 9
- 125000005936 piperidyl group Chemical group 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 125000002541 furyl group Chemical group 0.000 description 8
- 239000000499 gel Substances 0.000 description 8
- 125000005843 halogen group Chemical group 0.000 description 8
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 125000003226 pyrazolyl group Chemical group 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 150000001336 alkenes Chemical class 0.000 description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
- 125000004494 ethyl ester group Chemical group 0.000 description 7
- 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 description 7
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
- 125000002971 oxazolyl group Chemical group 0.000 description 7
- DSNYFFJTZPIKFZ-UHFFFAOYSA-N propoxybenzene Chemical group CCCOC1=CC=CC=C1 DSNYFFJTZPIKFZ-UHFFFAOYSA-N 0.000 description 7
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 239000003456 ion exchange resin Substances 0.000 description 6
- 229920003303 ion-exchange polymer Polymers 0.000 description 6
- 229940017219 methyl propionate Drugs 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 5
- 239000004215 Carbon black (E152) Substances 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 5
- 125000005605 benzo group Chemical group 0.000 description 5
- 239000012964 benzotriazole Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 5
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 5
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 150000002430 hydrocarbons Chemical class 0.000 description 5
- 150000003053 piperidines Chemical class 0.000 description 5
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 5
- 235000015320 potassium carbonate Nutrition 0.000 description 5
- 235000019260 propionic acid Nutrition 0.000 description 5
- 125000002098 pyridazinyl group Chemical group 0.000 description 5
- 125000004076 pyridyl group Chemical group 0.000 description 5
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 5
- 125000005425 toluyl group Chemical group 0.000 description 5
- NQBWNECTZUOWID-UHFFFAOYSA-N (E)-cinnamyl (E)-cinnamate Natural products C=1C=CC=CC=1C=CC(=O)OCC=CC1=CC=CC=C1 NQBWNECTZUOWID-UHFFFAOYSA-N 0.000 description 4
- REIDAMBAPLIATC-UHFFFAOYSA-N 4-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=CC=C(C(O)=O)C=C1 REIDAMBAPLIATC-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- KLQNJBAFEFFWQZ-UHFFFAOYSA-N benzoic acid;dihydrochloride Chemical compound Cl.Cl.OC(=O)C1=CC=CC=C1 KLQNJBAFEFFWQZ-UHFFFAOYSA-N 0.000 description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- NQBWNECTZUOWID-QSYVVUFSSA-N cinnamyl cinnamate Chemical compound C=1C=CC=CC=1\C=C/C(=O)OC\C=C\C1=CC=CC=C1 NQBWNECTZUOWID-QSYVVUFSSA-N 0.000 description 4
- WOZVHXUHUFLZGK-UHFFFAOYSA-N dimethyl terephthalate Chemical compound COC(=O)C1=CC=C(C(=O)OC)C=C1 WOZVHXUHUFLZGK-UHFFFAOYSA-N 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
- YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 description 4
- 125000002757 morpholinyl group Chemical group 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 125000001400 nonyl 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])C([H])([H])[H] 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 150000002923 oximes Chemical class 0.000 description 4
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([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 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 4
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- WTFNSXYULBQCQV-UHFFFAOYSA-N $l^{1}-oxidanyloxymethane Chemical compound CO[O] WTFNSXYULBQCQV-UHFFFAOYSA-N 0.000 description 3
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 3
- VMKOFRJSULQZRM-UHFFFAOYSA-N 1-bromooctane Chemical compound CCCCCCCCBr VMKOFRJSULQZRM-UHFFFAOYSA-N 0.000 description 3
- QSBQHEHNHCBCAA-UHFFFAOYSA-N 3,4-dihydrooxathiine Chemical compound C1CC=COS1 QSBQHEHNHCBCAA-UHFFFAOYSA-N 0.000 description 3
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- C07K7/50—Cyclic peptides containing at least one abnormal peptide link
- C07K7/54—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
- C07K7/56—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring the cyclisation not occurring through 2,4-diamino-butanoic acid
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
本发明涉及下式(I)表示的新的多肽类化合物及其可药用的盐:其中R1的定义与说明书中相同,其具有抗微生物活性(尤其是抗真菌活性),对β-1,3-葡聚糖合成酶具有抑制作用,本发明还涉及它们的制备方法,含有它们的药物组合物,以及用于预防和/或治疗人类或动物中的传染病,包括卡氏肺囊虫感染(例如间质性浆细胞性肺炎)的方法。
Description
技术领域
本发明涉及可作为药物使用的新的多肽化合物及其可药用的盐。
发明背景
在美国专利5,376,634中公开了具有抗微生物活性(尤其是抗真菌活性)的多肽化合物及其可药用的盐。
发明内容
本发明涉及新的多肽化合物及其可药用的盐。
更具体地说,本发明涉及新的多肽化合物及其可药用的盐,它们具有抗微生物活性(尤其是抗真菌活性,其中真菌可以包括曲霉、隐球菌、念球菌、毛霉菌、放线菌、组织胞浆菌、皮肤真菌、马拉色霉菌、镰孢菌等)和对β-1,3-葡聚糖合酶的抑制作用,预期可用于人类或动物的卡氏肺囊虫感染(例如间质性浆细胞性肺炎)的预防和/或治疗,本发明还涉及制备它们的方法,含有这些化合物的药物组合物,以及预防和/或治疗人或动物的传染病,包括卡氏肺囊虫感染(例如间质性浆细胞性肺炎),的方法。
本发明中使用的目标多肽化合物是新化合物,它可以用以下通式(I)表示:
其中R1是:
被含有至少一个氮原子并且可以有一个或多个合适取代基的不饱和6元杂单环基取代的低级烷酰基;
被可以有一个或多个合适取代基的1,2,3,4-四氢异喹啉取代的低级烷酰基;
被含有至少一个氧原子并且可以有一个或多个合适取代基的不饱和稠合杂环基取代的低级烷酰基;
被含有1-3个硫原子并且可以有一个或多个合适取代基的不饱和稠合杂环基取代的低级烷酰基;
被含有2个或更多氮原子并且可以有一个或多个合适取代基的不饱和稠合杂环基取代的低级烷酰基;
被含有至少一个氮原子并且可以有一个或多个合适取代基的3-8元饱和杂单环基取代的低级烷酰基;
被可以有一个或多个合适取代基的芳基取代的芳基(低级)烯酰基;
可以有一个或多个高级烷氧基的萘基(低级)烯酰基;
可以有一个或多个合适取代基的低级炔酰基;
被带有高级烷氧基的萘基取代的(C2-C6)烷酰基;
被带有一个或多个合适取代基的芳基取代的芳基(C2-C6)烷酰基,其中该芳基(C2-C6)烷酰基可以有一个或多个合适的取代基;
被可以有一个或多个合适取代基的杂环基取代的芳酰基,其中该芳酰基可以有一个或多个合适的取代基;
被带有杂环(高级)烷氧基的芳基取代的芳酰基,其中该杂环基可以有一个或多个合适的取代基;
被带有低级烷氧(高级)烷氧基的芳基取代的芳酰基;
被带有低级链烯基(低级)烷氧基的芳基取代的芳酰基;
被2个低级烷氧基取代的芳酰基;
被带有低级烷基的芳基取代的芳酰基;
被带有高级烷基的芳基取代的芳酰基;
可以有一个或多个合适取代基的芳氧基(低级)烷酰基;
可以有一个或多个合适取代基的芳基(低级)烷氧基(低级)烷酰基;
可以有一个或多个合适取代基的芳氨基(低级)烷酰基;
被带有低级烷基和芳基的吡唑基取代的低级烷酰基,该芳基带有高级烷氧基;
低级烷氧基(高级)烷酰基,其中的高级烷酰基可以有一个或多个合适的取代基;
被带有杂环氧基的芳基取代的芳酰基,其中的杂环氧基可以有一个或多个合适的取代基;
被带有低级烷基的环(低级)烷基取代的芳酰基;
带有高级烷基的吲哚基羰基;
带有低级烷基的萘甲酰基;
带有高级烷基的萘甲酰基;
带有低级烷氧基(高级)烷氧基的萘甲酰基;
被带有低级烷氧基(低级)烷氧基(高级)烷氧基的芳基取代的芳酰基;
被带有低级烷氧基(低级)烷氧基的芳基取代的芳酰基;
被芳基取代的芳酰基,该芳基有带有低级烷氧基的芳基取代基;
被芳基取代的芳酰基,该芳基有带有低级烷氧基(低级)烷氧基的芳基取代基;
被带有杂环氧基(高级)烷氧基的芳基取代的芳酰基;
被带有芳氧基(低级)烷氧基的芳基取代的芳酰基;
被带有杂环羰基(高级)烷氧基的芳基取代的芳酰基;
被带有芳基的噁唑基取代的低级烷酰基,该芳基带有高级烷氧基。
被带有芳基的呋喃基取代的低级烷酰基,该又被带有低级烷氧基的芳基取代;
被带有氧基和芳基的三唑基取代的低级烷酰基,该芳基带有高级烷基;
带有羟基的高级烷酰基;
带有芳基(低级)烷基和羟基的高级烷酰基;
3-甲基-十三烯酰基;或
被带有高级烷氧基的芳基取代的(C2-C6)烷酰基,其中的(C2-C6)烷酰基可以有氨基或被保护的氨基。
这种新的多肽化合物(I)及其可药用的盐可以通过在以下反应方案中示例说明的方法制备,或是通过R1中氨基保护基的消去反应制备。
方法1
或其在氨基上的活性
衍生物或它们的盐
或其盐
其中R1的定义如上。
目标多肽化合物(I)的合适的可药用盐是常规的无毒盐,可以包括与碱形成的盐或酸加成盐,例如与无机碱形成的盐,如碱金属盐(例如钠盐、钾盐等)、碱土金属盐(如钙盐、镁盐等)、铵盐;与有机碱形成的盐,如有机胺盐(例如三乙胺盐、吡啶盐、甲基吡啶盐、乙醇胺盐、三乙醇胺盐、二环己胺盐、N,N’-二苄基乙二胺盐等);无机酸加成盐(例如盐酸盐、氢溴酸盐、硫酸盐、磷酸盐等);有机羧酸磺酸加成盐(例如甲酸盐、乙酸盐、三氟乙酸盐、马来酸盐、酒石酸盐、富马酸盐、甲磺酸盐、苯磺酸盐、甲苯磺酸盐等);与碱性或酸性氨基酸(例如精氨酸、天冬氨酸、谷氨酸等)形成的盐。
在对本发明说明书的以上和随后的说明中,本发明打算包括在发明范围内的各种定义的合适实例及说明详细解释如下:
“低级”一词,除非另外指明,是指有1至6个碳原子的基团。
“高级”一词,除非另外指明,是指有7至20个碳原子的基团。
“一个或多个”的合适实例可以是数目1至6,其中优选的可以是数目1至3。
“低级烷酰基”的合适实例可以包括直链或支链的烷酰基,例如甲酰基、乙酰基、2-甲基乙酰基、2,2-二甲基乙酰基、丙酰基、丁酰基、异丁酰基、戊酰基、2,2-二甲基丙酰基、己酰基等。
在诸如“被含有至少一个氮原子而且可以有一个或多个合适取代基的不饱和6元杂单环基取代的低级烷酰基”、“被可以有一个或多个合适取代基的1,2,3,4-四氢异喹啉取代的低级烷酰基”等基团中,“合适取代基”的合适实例可以包括如下所述的低级烷氧基,如下所述的高级烷氧基,如下所述的低级烷基,如下所述的高级烷基,高级烷氧基(低级)烷基,低级烷氧基羰基,氧基,可以有一个或多个低级烷氧基的芳基,可以有一个或多个高级烷氧基的芳基,可以有一个或多个低级烷基的芳基,可以有一个或多个高级烷基的芳基,被可以有一个或多个低级烷氧基的芳基取代的芳基,被可以有一个或多个高级烷氧基的芳基取代的芳基,被可以有一个或多个低级烷基的芳基取代的芳基,被可以有一个或多个高级烷基的芳基取代的芳基,可以有一个或多个低级烷氧基的芳酰基,可以有一个或多个高级烷氧基的芳酰基,可以有一个或多个低级烷基的芳酰基,可以有一个或多个高级烷基的芳酰基,可以有一个或多个低级烷氧基的杂环基,可以有一个或多个高级烷氧基的杂环基,带有杂环(高级)烷氧基的芳基,可以有带有高级烷氧基的芳基的杂环基,可以有带有低级烷氧基(高级)烷氧基的芳基的杂环基,可以有带有低级烷氧基的芳基的杂环基,低级烷氧基(低级)烷基,卤代(低级)烷氧基,低级链烯氧基,卤代(高级)烷氧基,低级烷氧(高级)烷氧基,可以有一个或多个低级烷氧基(低级)烷氧基的芳基,杂环基,可以有一个或多个低级烷氧基(高级)烷氧基的芳基,可以有一个或多个高级烯氧基的芳基,可以带有芳基的环(低级)烷基,被可以带有低级烷基和氧基的杂环基取代的芳基,可以带有一个或多个低级烷基的环(低级)烷基,可以带有环(低级)烷基的芳基,可以带有杂环基的芳基等。
“低级烷氧基”的合适实例可以包括直链或支链的低级烷氧基,例如甲氧基、乙氧基、丙氧基、异丙氧基、丁氧基、异丁氧基、叔丁氧基、戊氧基、叔戊氧基、新戊氧基、己氧基、异己氧基等,其中优选的是甲氧基、乙氧基、丙氧基、丁氧基、戊氧基、己氧基和异己氧基。
“高级烷氧基”的合适实例可以包括直链或支链的高级烷氧基,例如庚氧基、辛氧基、3,5-二甲基辛氧基、3,7-二甲基辛氧基、壬氧基、癸氧基、十一烷氧基、十二烷氧基、十三烷氧基、十四烷氧基、十六烷氧基、十七烷氧基、十八烷氧基、十九烷氧基、二十烷氧基等,其中优选的是(C7-C14)烷氧基,更优选的是庚氧基和辛氧基。
“低级烷基”的合适实例包括直链或支链的有1-6个碳原子的烷基,例如甲基、乙基、丙基、异丙基、丁基、异丁基、仲丁基、叔丁基、戊基、叔戊基、新戊基、己基、异己基等,其中优选甲基、戊基、己基和异己基。
“高级烷基”的合适实例包括有7-20个碳原子的直链或支链烷基,例如庚基、辛基、3,5-二甲基辛基、3,7-二甲基辛基、壬基、癸基、十一烷基、十二烷基、十三烷基、十四烷基、十五烷基、十六烷基、十七烷基、十八烷基、十九烷基、二十烷基等,其中优选的是(C7-C14)烷基,更为优选的是庚基、辛基、壬基和癸基。
“芳香基”和“芳基”部分的合适实例包括可以带有低级烷基的苯基(例如苯基、2,4,6-三苯甲基、甲苯基等)、萘基、蒽基等,其中优选苯基和萘基。
“芳酰基”的合适实例可以包括苯甲酰基、甲苯酰基、萘甲酰基、蒽甲酰基等,其中优选苯甲酰基和萘甲酰基。
“杂环基”和“杂环”部分的合适实例可以包括含1-4个氮原子的3-8元(优选5或6元)不饱和杂单环基,例如吡咯基、吡咯啉基、咪唑基、吡唑基、吡啶基、二氢吡啶基、嘧啶基、吡嗪基、哒嗪基、三唑基(例如4H-1,2,4-三唑基,1H-1,2,3-三唑基、2H-1,2, -三唑基等)、四唑基(例如,1H-四唑基、2H-四唑基等)等;
含1-4个氮原子的饱和的3-8元(优选5或6元)杂单环基,例如吡咯烷基、咪唑烷基、哌啶基、哌嗪基等;
含1-4个氮原子的不饱和的稠合杂环基,例如吲哚基、异吲哚基、二氢吲哚基、吲嗪基、苯并咪唑基、喹啉基、异喹啉基、吲唑基、苯并三唑基等;
含1-2个氧原子和1-3个氮原子的不饱和的3-8元(优选5或6元)杂单环基,例如,噁唑基、异噁唑基、噁二唑基(如1,2,4-噁二唑基、1,3,4-噁二唑基、1,2,5-噁二唑基等)等;
含1-2个氧原子和1-3个氮原子的饱和的3-8元(优选5或6元)杂单环基,例如吗啉基、斯德酮基等;
含1-2个氧原子和1-3个氮原子的不饱和的稠合杂环基,例如苯并噁唑基、苯并噁二唑基等;
含1-2个硫原子和1-3个氮原子的不饱和的3-8元(优选5或6元)杂单环基,例如,噻唑基、异噻唑基、噻二唑基(如1,2,3-噻二唑基、1,2,4-噻二唑基、1,3,4-噻二唑基、1,2,5-噻二唑基等)、二氢噻嗪基等;
含1-2个硫原子和1-3个氮原子的饱和的3-8元(优选5或6元)杂单环基,例如噻唑烷基等;
含1-2个硫原子的不饱和的3-8元(优选5或6元)杂单环基,例如噻吩基、二氢二硫杂环己二烯基(dihydrodithiinyl)、dihydrodithionyl等;
含1-2个硫原子和1-3个氮原子的不饱和的稠合杂环基,例如,苯并噻唑基、苯并噻二唑基等;
含一个氧原子的不饱和的3-8元(优选5或6元)杂单环基,例如呋喃基等;
含一个氧原子的饱和的3-8元(优选5或6元)杂单环基,例如四氢呋喃基、四氢吡喃基等;
含一个氧原子和1-2个硫原子的不饱和的3-8元(优选5或6元)杂单环基,例如二氢氧硫杂环己二烯基等;
含1-2个硫原子的不饱和的稠合杂环基,例如苯并噻吩基、苯并二硫杂环己二烯基等;
含一个氧原子和1-2个硫原子的不饱和的稠合杂环基,例如苯并氧硫杂环己二烯基等。
“卤素”的合适实例可以包括氟、氯、溴和碘。
“低级烯氧基”的合适实例可以包括乙烯氧基、1-(或2-)丙烯氧基、1-(或2-或3-)丁烯氧基、1-(或2-或3-或4-)戊烯氧基、1-(或2-或3-或4-或5-)己烯氧基等,其中优选(C2-C6)烯氧基,最优选的是5-己烯氧基。
“高级烯氧基”的合适实例包括(C7-C20)烯氧基,其中优选的是6-庚烯氧基和7-辛烯氧基。
“环(低级)烷基”的合适实例可以包括环丙基、环丁基、环戊基、环己基等,其中优选的是环(C4-C6)烷基,最优选的是环己基。
“高级烷酰基”的合适实例可以包括庚酰基、辛酰基、壬酰基、癸酰基、十一烷酰基、十二烷酰基、十三烷酰基、十四烷酰基、十五烷酰基、十六烷酰基、十七烷酰基、十八烷酰基、十九烷酰基、二十烷酰基等,其中优选(C7-C20)烷酰基,最优选的是十六烷酰基。
“芳基(低级)烷基”的合适实例可以包括苄基、苯乙基、苯丙基、苯丁基、苯戊基、苯己基、萘甲基、萘乙基、萘丙基、萘丁基、萘戊基、萘己基等,其中优选苯基(C1-C4)烷基,最优选的是苄基。
“被保护的氨基”的合适实例可以包括低级或高级的烷氧羰基氨基(例如甲氧羰基氨基、乙氧羰基氨基、叔丁氧羰基氨基、叔戊氧羰基氨基、庚氧羰基氨基等),芳基(低级)烷氧羰基氨基〔例如,苯基(低级)烷氧羰基氨基(如苄氧羰基氨基等)等〕,被可以有合适取代基(如苄基、三苯甲基)的常规保护基(如芳基(低级)烷基)取代的氨基等,其中优选苯基(低级)烷氧羰基氨基,最优选的是苄氧羰基氨基。
在术语“被含有至少一个氮原子并且可以有一个或多个合适取代基的不饱和6元杂单环取代的低级烷酰基”中,“低级烷酰基”的合适实例可以参照前述的“低级烷酰基”,其中优选的是(C1-C4)烷酰基,最优选的是甲基。
在术语“被含有至少一个氮原子并且可以有一个或多个合适取代基的不饱和的6元杂单环基取代的低级烷酰基”一词中,“含至少一个氮原子的不饱和6元杂单环基”的合适实例可以包括:吡啶基、二氢吡啶基、嘧啶基、吡嗪基、哒嗪基、三嗪基(例如,4H-1,2,4-三嗪基、1H-1,2,3三嗪基等)、四嗪基(例如1,2,4,5-四嗪基、1,2,3,4-四嗪基等)等,其中优选的是含1到3个氮原子的不饱和的6元杂单环基,最优选的是吡啶基和哒嗪基。
在术语“被含有至少一个氮原子并且可以有一个或多个合适取代基的不饱和的6元杂单环基取代的低级烷酰基”一词中,“合适取代基”的合适实例可以参照上述的“合适的取代基”,其中优选的是高级烷氧基、高级烷氧(低级)烷基、可以有带有高级烷氧基的芳基的杂环基、可以带有一个或多个高级烷氧基的芳基、被可以带有低级烷氧基的芳基取代的芳基、可以有带有低级烷氧基(高级)烷氧基的芳基的杂环基,以及可以有带有低级烷氧基的芳基的杂环基,其中更优选的是(C7-C14)烷氧基、(C7-C14)烷氧基(C1-C4)烷基、含有至少1个氮原子并且可以带有一个有1-3个(C7-C14)烷氧基的苯基的3-8元饱和的杂单环基、可以有1-3个(C7-C14)烷氧基的苯基、被可以有1-3个(C3-C6)烷氧基的苯基取代的苯基、含至少一个氮原子并且可以有带有(C1-C4)烷氧基(C7-C14)烷氧基的苯基的3-8元饱和杂单环基、以及含至少一个氮原子并且可以有带有1-3个(C3-C6)烷氧基的苯基的3-8元饱和杂单环基,最为优选的是辛氧基、辛氧甲基、被带有庚氧基或辛氧基的苯基取代的哌嗪基、带有庚氧基的苯基、被带有丁氧基的苯基取代的苯基、被带有甲氧辛氧基的苯基取代的哌嗪基和被带有己氧基的苯基取代的哌嗪基。
在术语“被可以有一个或多个合适取代基的1,2,3,4-四氢异喹啉取代的低级烷酰基”中,“低级烷酰基”的合适实例可以参照前述的“低级烷酰基”,其中优选的是(C1-C4)烷酰基,更为优选的是甲酰基。
在术语“被可以有一个或多个合适取代基的1,2,3,4-四氢异喹啉取代的低级烷酰基”中的“合适取代基”的合适实例,可以参照上述的“合适取代基”,其中优选低级烷氧基、高级烷氧基、低级烷基、高级烷基和低级烷氧羰基,更优选的是(C7-C14)烷氧基和(C1-C4)烷氧羰基,最优选的是辛氧基和叔丁氧羰基。
在术语“被含有至少一个氧原子而且可以有一个或多个合适取代基的不饱和稠合杂环基取代的低级烷酰基”中,“低级烷酰基”的合适实例可以参照上述的“低级烷酰基”,其中优选(C1-C4)烷酰基,更为优选的是甲酰基。
在术语“被含有至少一个氧原子而且可以有一个或多个合适取代基的不饱和稠合杂环基的低级烷酰基”中,“含有至少一个氧原子不饱和稠合杂环基”的合适实例可以包括含一个或多个氧原子并可任选地有另外的非氧杂原子的不饱和的稠合杂环基,其中优选的是含1-3个氧原子的不饱和的稠合杂环基、含1-2个氧原子和1-2个硫原子的不饱和的稠合杂环基和含1-3个氧原子与1-3个氮原子的不饱和的稠合杂环基,更优选的是苯并〔b〕呋喃基、异苯并呋喃基、苯并吡喃基、呫吨基、苯并噁唑基、苯并噁二唑基、二氢氧硫杂环己二烯基、苯并氧硫杂环己二烯基等,最优选的是苯并〔b〕呋喃基、苯并吡喃基和苯并噁唑基。
在术语“被含有至少一个氧原子并且可以有一个或多个合适取代基的不饱和的稠合杂环基取代的低级烷酰基”中,“合适的取代基”的合适实例可以参照前述的“合适取代基”,其中优选的是低级烷氧基、高级烷氧基、低级烷基、高级烷基、氧基、可以带有一个或多个低级烷氧基的芳基、可以带有一个或多个高级烷氧基的杂环基、被可以带有一个或多个低级烷基的芳基取代的芳基,更优选的是(C7-C14)烷氧基、(C1-C4)烷基、(C7-C14)烷基、氧基、可以带有1-3个(C3-C6)烷氧基的苯基、含有至少一个氮原子并且可以有1-3个(C7-C14)烷氧基的不饱和的6元杂单环基、以及被可以有1-3个(C3-C6)烷基的苯基取代的苯基,最优选的是辛氧基、甲基、壬基、氧基、带有己氧基的苯基、带有辛氧基的吡啶基以及被带有己基的苯基取代的苯基。
在术语“被含有1-3个硫原子并且可以有一个或多个合适取代基的不饱和稠合杂环基取代的低级烷酰基”中的“低级烷酰基”的合适实例可以参照上述的“低级烷酰基”,其中优选的是(C1-C4)烷酰基,更为优选的是甲酰基。
在术语“被含有1-3个硫原子并且可以有一个或多个合适取代基的不饱和稠合杂环基取代的低级烷酰基”中,“含1-3个硫原子的不饱和稠合杂环基”的合适实例,可以包括只含1-3个硫原子的不饱和稠合杂环基,其中优选苯并噻吩基和苯并二硫杂环己二烯基,最优选的是苯并噻吩基。
在术语“被含有1-3个硫原子并且可以有一个或多个合适取代基的不饱和稠合杂环基取代的低级烷酰基”中的“合适取代基”的合适实例可以参照前述的“合适取代基”,其中优选低级烷氧基、高级烷氧基、低级烷基和高级烷基,更为优选的是(C7-C14)烷氧基,最优选的是辛氧基。
在术语“被含有2个或更多氮原子并且可以有一个或多个合适取代基的不饱和稠合杂环基取代的低级烷酰基”中,“低级烷酰基”的合适实例可以参照前述的“低级烷酰基”,其中优选的是(C1-C4)烷酰基,最优选的是甲酰基。
在术语“被含有2个或多个氮原子并且可以有一个或多个合适取代基的不饱和稠合杂环基取代的低级烷酰基”中,“含2个或多个氮原子的不饱和的稠合杂环基”的合适实例可以包括1H-吲唑基、嘌呤基、2,3-二氮杂萘基、苯并咪唑基、1,5-二氮杂萘基、喹喔啉基、喹唑啉基、1,2-二氮杂萘基、蝶啶基等,其中最优选的是苯并咪唑基。
在术语“被含有2个或更多氮原子并且可以有一个或多个合适取代基的不饱和稠合杂环基取代的低级烷酰基”中,“合适取代基”的合适实例可以参照前述的“合适取代基”,其中优选的是低级烷氧基、高级烷氧基、低级烷基、高级烷基、可以有一个或多个低级烷氧基的芳基和可以有一个或多个高级烷氧基的芳基,更为优选的是(C7-C14)烷基和可以带有1-3个(C1-C6)烷氧基的苯基,最为优选的是壬基和可以带有己氧基的苯基。
在术语“被含有至少一个氮原子并且可以有一个或多个合适取代基的饱和的3-8元杂单环基取代的低级烷酰基”中,“低级烷酰基”的合适实例可以参照前述的“低级烷酰基”,其中优选的是(C1-C4)烷酰基,更为优选的是甲酰基。
在术语“被含有至少一个氮原子并且可以有一个或多个合适取代基的饱和的3-8元杂单环基取代的低级烷酰基”中,“含有至少一个氮原子的饱和的3-8元杂单环基”的合适实例可以包括吡咯烷基、咪唑烷基、哌啶基、哌嗪基、吡唑烷基、吗啉基、硫代吗啉基等,其中优选的是哌啶基和哌嗪基。
在术语“被含有至少一个氮原子并且可以有一个或多个合适取代基的饱和的3-8元杂单环基取代的低级烷酰基”中,“合适取代基”的合适实例可以包括低级烷氧基、高级烷氧基、高级烷氧基(低级)烷基、低级烷基、高级烷基、氧基、可以带有一个或多个低级烷氧基的芳基、可以带有一个或多个高级烷氧基的芳基、可以带有一个或多个低级烷基的芳基、可以带有一个或多个高级烷基的芳基、可以带有一个或多个低级烷氧基的芳酰基、可以带有一个或多个高级烷氧基的芳酰基、可以带有一个或多个低级烷基的芳酰基、可以带有一个或多个高级烷基的芳酰基等,其中优选的是可以有一个或多个低级烷氧基的芳基、可以有一个或多个高级烷氧基的芳基、可以有一个或多个低级烷氧基的芳酰基和可以有一个或多个高级烷氧基的芳酰基,更为优选的是可以有1-3个高级烷氧基的芳基和可以有1-3个高级烷氧基的芳酰基,进一步优选的是可以有1-3个(C7-C14)烷氧基的苯基和可以有1-3个(C7-C14)烷氧基的萘甲酰基最优选的是可以带有辛氧基的苯基和可以带有庚氧基的萘甲酰基。
在术语“被可以有一个或多个合适取代基的芳基取代的芳基(低级)烯酰基”中,“芳基(低级)烯酰基”的合适实例可以包括苯基(低级)烯酰基(例如,3-苯基丙烯酰基、(2-或3-或4-)苯基(2-或3-)丁烯酰基、3-苯基甲基丙烯酰基、(2-或3-或4-或5-)苯基(2-或3-或4-)戊烯酰基、(2-或3-或4-或5-或6-)苯基(2-或3-或4-或5-)己烯酰基等)、萘基(低级)烯酰基(例如,3-萘基丙烯酰基、(2-或3-或4-)萘基(2-或3-)丁烯酰基、(2-或3-或4-或5-)萘基(2-或3-或4-)戊烯酰基、(2-或3-或4-或5-或6-)萘基(2-或3-或4-或5-)己烯酰基等)等,其中优选3-苯基丙烯酰基和3-甲基-3-苯基丙烯酰基。
在术语“被可以有一个或多个合适取代基的芳基取代的芳基(低级)烯酰基”中,“合适取代基”的合适实例可以参照前述的“合适取代基”,其中优选的是低级烷氧基、低级烷基、高级烷基、低级烷氧基(低级)烷基、卤代(低级)烷氧基、低级烯氧基、卤代(高级)烷氧基和低级烷氧基(高级)烷氧基,更为优选的是(C1-C6)烷氧基、(C1-C6)烷基、(C7-C14)烷基、(C1-C4)烷氧基(C3-C6)烷基、卤代(C3-C6)烷氧基、(C3-C6)烯氧基、卤代(C7-C14)烷氧基和(C1-C4)烷氧基(C7-C14)烷氧基,最为优选的是戊氧基、庚基、戊基、甲氧基己基、氟代己氧基、异己氧基、5-己烯氧基、卤代庚氧基、甲氧基庚氧基、甲氧基辛氧基和丁氧基。
在术语“可以带有一个或多个高级烷氧基的萘基(低级)烯酰基”中,“萘基(低级)烯酰基”的合适实例可包括3-萘基丙烯酰基、(2-或3-或4-)萘基(2-或3-)丁烯酰基、(2-或3-或4-或5-)萘基(2-或3-或4-)戊烯酰基、(2-或3-或4-或5-或6-)萘基(2-或3-或4-或5-)己酰基等,其中优选的是3-萘基丙烯酰基。
在术语“可以有一个或多个合适取代基的低级炔酰基”中的“低级炔酰基”的合适实例可以包括2-丙炔酰基、(2-或3-)丁炔酰基、(2-或3-或4-)戊炔酰基、(2-或3-或4-或5-)己炔酰基等,其中优选2-丙炔酰基。
在术语“可以有一个或多个合适取代基的低级炔酰基”中的“合适取代基”的合适实例可以参照前述的“合适取代基”,其中优选的是可以有一个或多个低级烷氧基的芳基、可以有一个或多个高级烷氧基的芳基、被可以有一个或多个低级烷基的芳基取代的芳基和被可以有一个或多个高级烷基的芳基取代的芳基,更优选的是被可以有1-3个低级烷基的芳基和可以有1-3个高级烷氧基的芳基取代的芳基,进一步优选的是被可以有1-3个(C1-C6)烷基的苯基和可以有1-3个(C7-C14)烷氧基的苯基取代的苯基,最优选的是被可以带有戊基的苯基和可以带有庚氧基的萘基取代的苯基。
在术语“被带有一个或多个合适取代基的芳基取代的芳基(C2-C6)烷酰基,其中芳基(C2-C6)烷酰基可以有一个或多个合适取代基”中,“芳基(C2-C6)烷酰基”的合适实例可以包括苯基(C2-C6)烷酰基〔例如,苯乙酰基、(2-或3-)苯丙酰基、(2-或3-或4-)苯丁酰基、(2-或3-或4-或5-)苯戊酰基、(2-或3-或4-或5-或6-)苯己酰基等〕、萘基(C2-C6)烷酰基〔例如,萘乙酰基、(2-或3-)萘丙酰基、(2-或3-或4-)萘丁酰基、(2-或3-或4-或5-)萘戊酰基、(2-或3-或4-或5-或6-)萘己酰基等〕等,其中优选2-苯乙酰基和3-苯丙酰基。
在术语“被带有一个或多个合适取代基的芳基取代的芳基(C2-C6)烷酰基,其中芳基(C2-C6)烷酰基可以有一个或多个合适取代基”中,“合适取代基”的合适实例可以包括低级烷氧基、高级烷氧基、低级烷基、高级烷基、高级烷氧基(低级)烷基、氧基、带有一个或多个低级烷氧基的芳基、带有一个或多个高级烷氧基的芳基、带有一个或多个低级烷基的芳基、带有一个或多个高级烷基的芳基、被带有一个或多个低级烷氧基的芳基取代的芳基、被带有一个或多个高级烷氧基的芳基取代的芳基、被带有一个或多个低级烷基的芳基取代的芳基、被带有一个或多个高级烷基的芳基取代的芳基、带有一个或多个低级烷氧基(低级)烷氧基的芳基等,其中优选的是低级烷氧基、高级烷氧基、低级烷基、高级烷基和带有1-3个低级烷氧基(低级)烷氧基的苯基,更为优选的是(C1-C6)烷氧基、(C1-C6)烷基、(C7-C14)烷基和带有(C1-C4)烷氧基(C3-C6)烷氧基的苯基,最优选的是戊氧基、戊基、庚基和带有甲氧戊氧基的苯基。
在术语“其中芳基(C2-C6)烷酰基可以有一个或多个合适取代基”中的“合适取代基”的合适实例可以是羟基、氧基、氨基和前述的“被保护的氨基”。
在术语“被带有高级烷氧基的萘基取代的(C2-C6)烷酰基”中,“(C2-C6)烷酰基”的合适实例可以包括乙酰基、丙酰基、丁酰基、戊酰基、己酰基等,其中优选的是丙酰基。
在术语“被带有高级烷氧基的萘基取代的(C2-C6)烷酰基”中,“高级烷氧基”的合适实例可以参照上述的“高级烷氧基”,其中优选的是(C7-C14)烷氧基,最优选的是庚氧基。
在术语“被可以有一个或多个合适取代基的杂环基取代的芳酰基,其中该芳酰基可以有一个或多个合适取代基”中,“芳酰基”的合适实例可以包括苯甲酰基,甲苯酰基、萘甲酰基等,其中优选的是苯甲酰基。
在术语“被可以有一个或多个合适取代基的杂环基取代的芳酰基,其中芳酰基可以有一个或多个合适取代基”中,“杂环基”的合适实例可以包括含1-4个氮原子的不饱和的3-8元(更优选5或6元)杂单环基,例如吡咯基、吡咯啉基、咪唑基、吡唑基、吡啶基、二氢吡啶基、嘧啶基、吡嗪基、哒嗪基、三唑基(例如4H-1,2,4-三唑基、1H-1,2,3-三唑基、2H-1,2,3-三唑基等)、四唑基(如1H-四唑基、2H-四唑基等)等;
含1-4个氮原子的饱和的3-8元(更优选5或6元)杂单环基,例如吡咯烷基、咪唑烷基、哌啶基、哌嗪基等;
含1-4个氮原子的不饱和的稠合杂环基,例如,吲哚基、异吲哚基、二氢吲哚基、吲嗪基、苯并咪唑基、喹啉基、异喹啉基、吲唑基、苯并三唑基等;
含1-2个氧原子和1-3个氮原子的不饱和的3-8元(优选5或6元)杂单环基,例如,噁唑基、异噁唑基、噁二唑基(如1,2,4-噁二唑基、1,3,4-噁二唑基、1,2,5-噁二唑基等)等;
含1-2个氧原子和1-3个氮原子的饱和的3-8元(优选5或6元)杂单环基,例如吗啉基、斯德酮基等;
含1-2个氧原子和1-3个氮原子的不饱和的稠合杂环基,例如苯并噁唑基、苯并噁二唑基等;
含1-2个硫原子和1-3个氮原子的不饱和的3-8元(优选5或6元)杂单环基,例如,噻唑基、异噻唑基、噻二唑基(如1,2,3-噻二唑基、1,2,4-噻二唑基、1,3,4-噻二唑基、1,2,5-噻二唑基等)、二氢噻嗪基等;
含1-2个硫原子和1-3个氮原子的饱和的3-8元(优选5或6元)杂单环基,例如噻唑烷基等;
含1-2个硫原子的不饱和的3-8元(优选5或6元)杂单环基,例如,噻吩基、二氢二硫杂环己二烯基、dihydrodithionyl等;
含1-2个硫原子和1-3个氮原子的不饱和的稠合杂环基,例如苯并噻唑基、苯并噻二唑基等;
含一个氧原子的不饱和的3-8元(优选5或6元)杂单环基,例如呋喃基等;
含一个氧原子的饱和的3-8元(优选5或6元)杂单环基,例如四氢呋喃基、四氢吡喃基等;
含一个氧原子和1-2个硫原子的不饱和的3-8元(优选5或6元)杂单环基,例如二氢氧硫杂环己二烯基等;
含1-2个硫原子的不饱和的稠合杂环基,例如苯并噻吩基、苯并二硫杂环己二烯基等;
含一个氧原子和1-2个硫原子的不饱和的稠合杂环基,例如苯并氧硫杂环己二烯基等;以及类似基团,
其中,优选的是含1-4个氮原子的饱和的3-8元杂单环基,含1-2个氧原子和1-3个氮原子的不饱和的3-8元杂单环基,含1-4个氮原子的不饱和的3-8元杂单环基,含1-2个硫原子和1-3个氮原子的不饱和的3-8元杂单环基,最为优选的是哌嗪基、异噁唑基、噁二唑基、噻二唑基、吡唑基、哌啶基、噁唑基和嘧啶基。
在术语“被可以有一个或多个合适取代基的杂环基取代的芳酰基,其中芳酰基可以有一个或多个合适取代基”中,“合适取代基”的合适实例可以参照前述的“合适取代基”,其中优选可以有1-3个高级烷氧基的芳基、可以有1-3个低级烷氧基的芳基、高级烷基、杂环基、可以有1-3个低级烷氧基(高级)烷氧基的芳基、可以有高级烯氧基的芳基、可以有带有低级烷氧基的芳基的杂环基、可以带有芳基的环(低级)烷基、可以带有1-3个低级烷基的芳基、可以带有环(低级)烷基的芳基、可以带有高级烯氧基的芳基、被可以带有低级烷基和氧基的杂环基取代的芳基、可以带有低级烷基的环(低级)烷基、被可以带有1-3个低级烷氧基的芳基取代的芳基、以及可以带有杂环基的芳基,更为优选的是可以带有1-3个(C7-C14)烷氧基的苯基、可以带有1-3个(C3-C6)烷氧基的苯基、(C7-C14)烷基、含1-4个氮原子的饱和的3-8元杂单环基、可以带有1-3个(C1-C4)烷氧基(C7-C14)烷氧基的苯基、可以带有(C7-C14)烯氧基的苯基、被带有(C3-C6)烷氧基的苯基取代的含1-4个氮原子的饱和的3-8元杂单环基、可以带有苯基的环(C3-C6)烷基、可以带有1-3个(C3-C6)烷基的苯基、可以带有环(C3-C6)烷基的苯基、可以带有(C7-C14)烯氧基的苯基、被可以带有(C3-C6)烷基和氧基的杂环基取代的苯基、可以带有(C3-C6)烷基的环(C3-C6)烷基、被可以带有1-3个(C1-C4)烷氧基的苯基取代的苯基、以及可以带有含1-4个氮原子的3-8元杂单环基的苯基,最优选的是带有辛氧基的苯基、带有戊氧基的苯基、带有己氧基的苯基、庚基、哌啶基、带有异己氧基的苯基、带有庚氧基的苯基、带有甲氧庚氧基的苯基、带有甲氧辛氧基的苯基、带有6-庚烯氧基的苯基、被带有己氧基的苯基取代的哌啶基、带有苯基的环己基、带有己基的苯基、带有环己基的苯基、带有7-辛烯氧基的苯基、被带有低级烷基和氧基的三唑基取代的苯基、带有戊基的环己基、带有甲氧辛氧基的苯基、壬基、被带有丙氧基的苯基取代的苯基和带有哌啶基的苯基。
在术语“其中芳酰基可以有一个或多个合适取代基”中的“合适取代基”的合适实例可以是卤素,其中优选的可以是氟和氯。
在术语“被带有杂环(高级)烷氧基的芳基取代的芳酰基,其中杂环基可以有一个或多个合适取代基”中,“芳酰基”的合适实例可以包括苯甲酰基、甲苯酰基、萘甲酰基、蒽甲酰基等,其中优选的是苯甲酰基。
在术语“被带有杂环(高级)烷氧基的芳基取代的芳酰基,其中的杂环基可以有一个或多个合适取代基”中,“杂环基”的合适实例可以参照此前对术语“被可以有一个或多个合适取代基的杂环基取代的芳酰基”示例说明的那些,其中优选的是含1-4个氮原子的不饱和的3-8元杂单单环基和含1-2个氧原子及1-3个氮原子的饱和的3-8元杂单环基,最优选的是三唑基、四唑基和吗啉基。
在术语“被带有杂环(高级)烷氧基的芳基取代的芳酰基,其中杂环基可以有一个或多个合适取代基”中,“(高级)烷氧基”部分的合适实例可以参照前述的“高级烷氧基”,其中优选的是(C7-C14)烷氧基,最优选的是辛氧基。
在术语“被带有杂环(高级)烷氧基的芳基取代的芳酰基,其中杂环基可以有一个或多个合适取代基”中,“芳基”的合适实例可以参照前述的“芳基”,其中优选苯基。
在术语“其中杂环基可以有一个或多个合适取代基”中的“合适取代基”的合适实例可以是低级烷基,其中优选甲基。
在术语“被带有低级烷氧基(高级)烷氧基的芳基取代的芳酰基”中,“芳酰基”的合适实例可以包括苯甲酰基、甲苯酰基、萘甲酰基、蒽甲酰基等,其中优选苯甲酰基。
在术语“被带有低级烷氧基(高级)烷氧基的芳基取代的芳酰基”中,“芳基”的合适实例可以参照前述的“芳基”,其中优选苯基。
在术语“被带有低级烷氧基(高级)烷氧基的芳基取代的芳酰基”中,“低级烷氧基(高级)烷氧基”的合适实例可以是甲氧庚氧基、甲氧辛氧基、甲氧壬氧基、甲氧癸氧基、乙氧庚氧基、乙氧辛氧基、乙氧壬氧基、乙氧癸氧基、乙氧十一烷氧基、丙氧十一烷氧基、丁氧十二烷氧基、戊氧十三烷氧基、己氧十四烷氧基、丙氧庚氧基、丙氧辛氧基、丙氧壬氧基、丁氧癸氧基等,其中优选(C1-C6)烷氧(C7-C14)烷氧基,更为优选的是甲氧辛氧基。
在术语“被带有低级烯基(低级)烷氧基的芳基取代的芳酰基”中,“芳酰基”的合适实例可以包括苯甲酰基、甲苯酰基、萘甲酰基、蒽甲酰基等,其中优选苯甲酰基。
在术语“被带有低级烯基(低级)烷氧基的芳基取代的芳酰基”中,“芳基”的合适实例可以参照前述的“芳基”,其中优选的是苯基。
在术语“被带有低级烯基(低级)烷氧基的芳基取代的芳酰基”中,“低级烷基(低级)烷氧基”的合适实例可以是乙烯基甲氧基、乙烯基乙氧基、乙烯基丙氧基、乙烯基丁氧基、乙烯基戊氧基、乙烯基己氧基、1-(或2-)丙烯基甲氧基、1-(或2-)丙烯基乙氧基、1-(或2-)丙烯基丙氧基、1-(或2-)丙烯基丁氧基、1-(或2-)丙烯基戊氧基、1-(或2-)丙烯基己氧基、1-(或2-或3-)丁烯基丁氧基、1-(或2-或3-)丁烯基己氧基、1-(或2-或3-或4-)戊烯基戊氧基、1-(或2-或3-或4-)戊烯基己氧基、1-(或2-或3-或4-或5-)己烯基丁氧基、1-(或2-或3-或4-或5-)己烯基己氧基等,其中优选的是(C2-C6)烯基(C1-C6)烷氧基,更优选的是乙烯基己氧基。
“被2个低级烷氧基取代的芳酰基”的合适实例可以包括被2个低级烷氧基取代的苯甲酰基和被2个低级烷氧基取代的萘甲酰基,其中优选被2个(C1-C6)烷氧基取代的苯甲酰基,最优选的是被2个戊氧基取代的苯甲酰基。
“被带有低级烷基的芳基取代的芳酰基”的合适实例可以包括被带有低级烷基的苯基取代的苯甲酰基、被带有低级烷基的萘基取代的苯甲酰基、被带有低级烷基的苯基取代的萘甲酰基、被带有低级烷基的萘基取代的萘甲酰基等,其中优选的是被带有(C1-C6)烷基的苯基取代的苯甲酰基,最优选的是被带有己基的苯基取代的苯甲酰基和被带有戊基的苯基取代的苯甲酰基。
“被带有高级烷基的芳基取代的芳酰基”的合适实例可以包括被带有高级烷基的苯基取代的苯甲酰基、被带有高级烷基的萘基取代的苯甲酰基、被带有高级烷基的苯基取代的萘甲酰基、被带有高级烷基的萘基取代的萘甲酰基等,其中优选的是被带有(C7-C14)烷基的苯基取代的苯甲酰基,最优选的是被带有庚基的苯基取代的苯甲酰基。
在术语“可以带有一个或多个合适取代基的芳氧基(低级)烷酰基”中,“芳氧基”部分的合适实例可以包括苯氧基、氧基、甲苯氧基、萘氧基、蒽氧基等,其中优选苯氧基。
在术语“可以有一个或多个合适取代基的芳氧基(低级)烷酰基”中,“低级烷酰基”部分的合适实例可以参照前述的“低级烷酰基”,其中优选的是甲酰基、乙酰基、2,2-二甲基乙酰基、丙酰基、丁酰基、异丁酰基和戊酰基、己酰基,更优选的是(C1-C6)烷酰基,最优选的是甲酰基、乙酰基、丙酰基和2,2-二甲基乙酰基。
在术语“可以有一个或多个合适取代基的芳氧基(低级)烷酰基”中,“合适取代基”的合适实例可以参照前述的“合适取代基”,其中优选(C7-C14)烷氧基,更为优选的是辛氧基。
在术语“可以有一个或多个合适取代基的芳基(低级)烷氧基(低级)烷酰基”中,“芳基(低级)烷氧基”的合适实例可以包括苯基(低级)烷氧基〔例如,苯基甲氧基、(1-或2-)苯基乙氧基、苯基丙氧基、2-苯基-1-甲基丙氧基、3-苯基-2,2-二甲基丙氧基、(1-或2-或3-或4-)苯基丁氧基、(1-或2-或3-或4-或5-)苯基戊氧基、(1-或2-或3-或4-或5-或6-苯基己氧基等〕、萘基(低级)烷氧基〔例如萘基甲氧基、(1-或2-)萘基乙氧基、1-萘基丙氧基、2-萘基-1-甲氧丙氧基、3-萘基-2,2-二甲基丙氧基、(1-或2-或3-或4-)萘基丁氧基、(1-或2-或3-或4-或5-)萘基戊氧基、(1-或2-或3-或4-或5-或6-)萘基己氧基等〕等,其中优选萘基(C1-C4)烷氧基,更为优选的是萘基甲氧基。
在术语“可以有一个或多个合适取代基的芳基(低级)烷氧基(低级)烷酰基”中,“(低级)烷酰基”部分的合适实例可以参照前述的“低级烷酰基”,其中优选的是(C1-C4)烷酰基,更优选的是甲酰基。
在术语“可以有一个或多个合适取代基的芳基(低级)烷氧基(低级)烷酰基”中,“合适取代基”的合适实例可以参照前述的“合适取代基”,其中优选的是低级烷氧基、高级烷氧基、低级烷基和高级烷基,更优选的是高级烷氧基,进一步优选的是(C7-C14)烷氧基,最优选的是庚氧基。
在术语“可以有一个或多个合适取代基的芳氨基(低级)烷酰基”中,“芳氨基”部分的合适实例可以包括苯氨基、氨基、甲苯氨基、萘氨基、蒽氨基等,其中优选苯氨基和萘氨基。
在术语“可以有一个或多个合适取代基的芳氨基(低级)烷酰基”中,“低级烷酰基”的合适实例可以参照前述的“低级烷酰基”,其中优选的是(C1-C4)烷酰基,更为优选的是甲酰基。
在术语“可以有一个或多个合适取代基的芳氨基(低级)烷酰基”中,“合适取代基”的合适实例可以参照上述的“合适取代基”,其中优选的是低级烷氧基、高级烷氧基、低级烷基、高级烷基、可以带有1-3个低级烷氧基的芳基和可以带有1-3个高级烷氧基的芳基,更为优选的是(C7-C14)烷氧基和可以带有1-3个(C7-C14)烷氧基的苯基,最优选的是庚氧基和可以带有庚氧基的苯基。
在术语“被带有低级烷基和带有高级烷氧基的芳基的吡唑基取代的低级烷酰基”中,“低级烷酰基”的合适实例可以参照前述的“低级烷酰基”,其中优选(C1-C4)烷酰基,最优选的是甲酰基。
在术语“被带有低级烷基和带有高级烷氧基的芳基的吡唑基取代的低级烷酰基”中,“低级烷基”的合适实例可以参照前述的“低级烷基”,其中优选(C1-C4)烷基,最优选的是甲基。
在术语“被带有低级烷基和带有高级烷氧基的芳基的吡唑基取代的低级烷酰基”中,“芳基”的合适实例可以参照前述的“芳基”,其中优选苯基。
在术语“被带有低级烷基和带有高级烷氧基的芳基的吡唑基取代的低级烷酰基”中,“高级烷氧基”的合适实例可以参照前述的“高级烷氧基”,其中优选(C7-C14)烷氧基,最优选的是辛氧基。
在术语“低级烷氧基(高级)烷酰基,其中高级烷酰基可以有一个或多个合适取代基”中,“低级烷氧基(高级)烷酰基”的合适实例可以是(C1-C4)烷氧基(C7-C20)烷酰基,其中优选甲氧十八烷酰基。
在术语“低级烷氧基(高级)烷酰基,其中高级烷酰基可以有一个或多个合适取代基”中,“合适取代基”的合适实例可以是氨基和前述的“被保护的氨基”,其中优选氨基和芳基(低级)烷氧羰基氨基,最优选的是氨基和苄氧羰基氨基。
在术语“被带有杂环氧基的芳基取代的芳酰基,其中杂环氧基可以有一个或多个合适取代基”中,“芳酰基”的合适实例可以参照前述的“芳酰基”,其中优选苯甲酰基。
在术语“被带有杂环氧基的芳基取代的芳酰基,其中杂环氧基可以有一个或多个合适取代基”中,“芳基”的合适实例可以参照前述的“芳基”,其中优选苯基。
在术语“被带有杂环氧基的芳基取代的芳酰基,其中杂环氧基可以有一个或多个合适取代基”中,“杂环”部分的合适实例可以参照前述的“杂环”部分,其中优选含1-4个氮原子的不饱和的3-8元杂单环基,最优选的是哒嗪基。
在术语“被带有杂环氧基的芳基取代的芳酰基,其中杂环氧基可以有一个或多个合适取代基”中,“合适取代基”的合适实例可以是芳基,其中优选苯基。
在术语“被带有低级烷基的环(低级)烷基取代的芳酰基”中,“芳酰基”的合适实例可以参照前述的“芳酰基”,其中优选的是苯甲酰基。
在术语“被带有低级烷基的环(低级)烷基取代的芳酰基”中,“环(低级)烷基”的合适实例可以参照前述的“环(低级)烷基”,其中优选环己基。
在术语“被带有低级烷基的环(低级)烷基取代的芳酰基”中,“低级烷基”的合适实例可以参照前述的“低级烷基”,其中优选戊基。
在术语“带有高级烷基的吲哚羰基”中,“高级烷基”的合适实例可以参照前述的“高级烷基”,其中优选癸基。
在术语“带有低级烷基的萘甲酰基”中,“低级烷基”的合适实例可以参照前述的“低级烷基”,其中优选己基。
在术语“带有高级烷基的萘甲酰基”中,“高级烷基”的合适实例可以参照前述的“高级烷基”,其中优选庚基。
在术语“带有低级烷氧基(高级)烷氧基的萘甲酰基”中,“低级烷氧基(高级)烷氧基”的合适实例可以是(C1-C4)烷氧基(C7-C14)烷氧基,其中优选甲氧辛氧基。
在术语“被带有低级烷氧基(低级)烷氧基(高级)烷氧基的芳基取代的芳酰基”、“被带有低级烷氧基(低级)烷氧基的芳基取代的芳酰基”、“被芳基取代的芳酰基,该芳基有带有低级烷氧基的芳基”、“被芳基取代的芳酰基,该芳基有带有低级烷氧基(低级)烷氧基的芳基”、“被带有杂环氧基(高级)烷氧基的芳基取代的芳酰基”、“被带有芳氧基(低级)烷氧基的芳基取代的芳酰基”和“被带有杂环羰基(高级)烷氧基的芳基取代的芳酰基”中,“芳酰基”的合适实例可以参照前述的“芳酰基”,其中优选苯甲酰基。
在上述术语中的“芳基”的合适实例可以参照前述的“芳基”,其中优选苯基。
在术语“被带有低级烷氧基(低级)烷氧基(高级)烷氧基的芳基取代的芳酰基”中,“低级烷氧基(低级)烷氧基(高级)烷氧基”的合适实例可以是(C1-C4)烷氧基(C1-C4)烷氧基(C7-C14)烷氧基,其中优选乙氧基乙氧辛氧基。
在术语“被带有低级烷氧基(低级)烷氧基的芳基取代的芳酰基”中,“低级烷氧基(低级)烷氧基”的合适实例可以是(C1-C4)烷氧基(C3-C6)烷氧基,其中优选丙氧己氧基。
在术语“被芳基取代的芳酰基,该芳基有带有低级烷氧基的苯基”中,“低级烷氧基”的合适实例可以是(C3-C6)烷氧基,其中优选丁氧基。
在术语“被芳基取代的芳酰基,该芳基有带有低级烷氧基(低级)烷氧基的苯基”中,“低级烷氧(低级)烷氧基”的合适实例可以是(C1-C4)烷氧基(C3-C6)烷氧基,其中优选甲氧戊氧基和甲氧己氧基。
在术语“被带有杂环氧基(高级)烷氧基的芳基取代的芳酰基”中,“杂环”部分的合适实例可以参照前述的“杂环”部分,其中优选含一个氧原子的饱和的3-8元杂单环基,最优选的是四氢吡喃基。
在术语“被带有杂环氧基(高级)烷氧基的芳基取代的芳酰基”中,“高级烷氧基”的合适实例可以是(C7-C14)烷氧基,其中优选辛氧基。
在术语“被带有芳氧基(低级)烷氧基的芳基取代的芳酰基”中,“芳氧基(低级)烷氧基”的合适实例可以是苯氧基(C3-C6)烷氧基,其中优选的是苯氧戊氧基。
在术语“被带有杂环羰基(高级)烷氧基的芳基取代的芳酰基”中,“杂环”部分的合适实例可以参照上述的“杂环”部分,其中优选含1-4个氮原子的饱和的3-8元杂单环基,最优选的是哌啶基。
在术语“被带有杂环羰基(高级)烷氧基的芳基取代的芳酰基”中,“高级烷氧基”部分的合适实例可以参照前述的“高级烷氧基”,其中优选(C7-C14)烷氧基,最为优选的是庚氧基。
在术语“被带有芳基的噁唑基取代的低级烷酰基,该芳基带有高级烷氧基”中,“低级烷酰基”的合适实例可以参照前述的“低级烷酰基”,其中优选(C1-C4)烷酰基,最优选的是甲酰基。
在术语“被带有芳基的噁唑基取代的低级烷酰基,该芳基带有高级烷氧基”中,“芳基”的合适实例可以参照前述的“芳基”,其中优选苯基。
在术语“被带有芳基的噁唑基取代的低级烷酰基,该芳基带有高级烷氧基”中,“高级烷氧基”的合适实例可以参照前述的“高级烷氧基”,其中优选(C7-C14)烷氧基,最优选的是辛氧基。
在术语“被带有芳基的呋喃基取代的低级烷酰基,该芳基被带有低级烷氧基的芳基取代”中,“低级烷酰基”的合适实例可以参照前述的“低级烷酰基”,其中优选(C1-C4)烷酰基,最优选的是甲酰基。
在术语“被带有芳基的呋喃基取代的低级烷酰基,该芳基被带有低级烷氧基的芳基取代”中,“芳基”的合适实例可以参照前述的芳基,其中优选苯基。
在“被带有芳基的呋喃基取代的低级烷酰基,该芳基被带有低级烷氧基的芳基取代”中,“低级烷氧基”的合适实例可以参照前述的“低级烷氧基”,其中优选(C1-C4)烷氧基,最优选的是丁氧基。
在术语“被三唑基取代的低级烷酰基,该三唑基带有氧基和有高级烷基的芳基”中,“低级烷酰基”的合适实例可以参照前述的“低级烷酰基”,其中优选的是(C1-C4)烷酰基,最优选的是甲酰基。
在术语“被三唑基取代的低级烷酰基,该三唑基带有氧基和有高级烷基的芳基”中,“高级烷基”的合适实例可以参照前述的“高级烷基”,其中优选(C7-C14)烷基,最优选的是辛基。
在术语“被三唑基取代的低级烷酰基,该三唑基带有氧基和有高级烷基的芳基”中,“芳基”的合适实例可以参照前述的芳基,其中优选苯基。
在术语“带有羟基的高级烷酰基”中,“高级烷酰基”的合适实例可以参照前述的“高级烷酰基”,其中优选(C7-C20)烷酰基,最优选的是十六烷酰基。
在术语“带有芳基(低级)烷基和羟基的高级烷酰基”中,“高级烷酰基”的合适实例可以参照前述的“高级烷酰基”,其中优选(C7-C20)烷酰基,最优选的是十六烷酰基。
在术语“带有芳基(低级)烷基和羟基的高级烷酰基”中,“芳基(低级)烷基”的合适实例可以参照前述的“芳基(低级)烷基”,其中优选苯基(C1-C4)烷基,最优选的是苄基。
在术语“被带有高级烷氧基的芳基取代的(C2-C6)烷酰基,其中(C2-C6)烷酰基可以有氨基或被保护的氨基”中,“(C2-C6)烷酰基”的合适实例可以包括乙酰基、丙酰基、丁酰基、戊酰基、己酰基等,其中优选乙酰基和丙酰基。
在术语“被带有高级烷氧基的芳基取代的(C2-C6)烷酰基,其中(C2-C6)烷酰基可以带有氨基或被保护的氨基”中, “芳基”的合适实例可以参照前述的“芳基”,其中优选苯基。
在术语“被带有高级烷氧基的芳基取代的(C2-C6)烷酰基,其中(C2-C6)烷酰基可以带有氨基或被保护的氨基”中,“高级烷氧基”的合适实例可以参照前述的“高级烷氧基”,其中优选(C7-C14)烷氧基,最优选的是辛氧基。
在术语“被带有高级烷氧基的芳基取代的(C2-C6)烷酰基,其中(C2-C6)烷酰基可以带有氨基或被保护的氨基”中,“被保护的氨基”的合适实例可以参照前述的“被保护的氨基”,其中优选芳基(低级)烷氧羰基氨基,最优选的是苄氧基羰基氨基。
下面详细解释本发明目标多肽化合物〔I〕或其盐的制备方法。
方法1
目标多肽化合物〔I〕或其盐可以通过化合物〔II〕或其在氨基上的活性衍生物或它们的盐与式〔III〕化合物或其在羧基上的活性衍生物或它们的盐反应来制备。
式〔III〕化合物在羧基上的合适的活性衍生物可以包括酰基卤化物、酸酐、活化的酰胺、活化的酯等。活性衍生物的合适实例可以是酰基氯;酰基叠氮;与一种酸形成的混合酸酐,例如取代的磷酸(如二烷基磷酸、苯基磷酸、二苯基磷酸、二苄基磷酸、卤代磷酸等)、二烷基亚磷酸、亚硫酸、硫代硫酸、硫酸、磺酸(如甲磺酸等)、脂族羧酸(如乙酸、丙酸、丁酸、异丁酸、新戊酸、戊酸、异戊酸、2-乙基丁酸、三氯乙酸等)或芳族羧酸(如苯甲酸等);对称的酸酐;与咪唑、4-取代的咪唑、二甲基吡唑、三唑、四唑或1-羟基-1H-苯并三唑形成的活化的酰胺;或活化的酯(例如氰甲基酯、甲氧基甲酯、二甲基亚氨基甲基〔(CH3)2N+=CH-〕酯、乙烯基酯、炔丙基酯、对硝基苯酯、2,4-二硝基苯酯、三氯苯基酯、五氯苯基酯、甲磺酰基苯基酯、苯基偶氮苯基酯、苯基硫代酸酯、对硝基苯基硫代酸酯、对甲酚基硫代酸酯、羧甲基硫代酸酯、吡喃基酯、吡啶基酯、哌啶基酯、8-喹啉基硫代酸酯等),或是与一种N-羟基化合物〔例如N,N-二甲基羟基胺、1-羟基-2-(1H)-吡啶酮、N-羟基丁二酰亚胺、N-羟基邻苯二甲酰亚胺、1-羟基-1H-苯并三唑等〕形成的活化的酯等。这些活性衍生物可以根据要使用的化合物〔III〕的要求任意地从中选择。
化合物〔III〕及其活性衍生物的合适的盐可以参照对于目标多肽化合物〔I〕示例说明的那些。
反应通常在常规溶剂中进行,例如水、醇(如甲醇、乙醇等)、丙酮、二噁烷、乙腈、氯仿、二氯甲烷、二氯乙烷、四氢呋喃、乙酸乙酯、N,N-二甲基甲酰胺、吡啶或者对反应无不利影响的任何有机溶剂。这些常规溶剂也可以与水混合使用。
在此反应中,当化合物〔III〕是以游离酸或其盐的形式使用时,反应优选在有常规的缩合剂存在下进行,例如N,N’-二环己基碳化二亚胺;N-环己基-N’-吗啉基乙基碳化二亚胺;N-环己基-N’-(4-二乙氨基环己基)碳化二亚胺;N,N’-二乙基碳化二亚胺、N,N’-二异丙基碳化二亚胺;N-乙基-N’-(3-二甲氨基丙基)碳化二亚胺;N,N’-羰基双-(2-甲基咪唑);五亚甲基烯酮-N-环己基亚胺;二苯基烯酮-N-环己基亚胺;乙氧基乙炔;1-烷氧基-2-氯乙烯;亚磷酸三烷基酯;聚磷酸乙酯;聚磷酸异丙酯;磷酰氮;三氯化磷;亚硫酰氯,草酰氯;卤代甲酸低级烷基酯(例如氯甲酸乙酯、氯甲酸并丙酯等);三苯膦;2-乙基-7-羟基苯并异噁唑鎓盐;2-乙基-5-(间磺基苯基)异噁唑鎓氢氧化物分子内盐;1-(对氯苯磺酰氧基)-6-氯-1H-苯并三唑,通过N,N-二甲基甲酰胺与亚硫酰氯、碳酰氯、氯甲酸三氯甲酯、磷酰氯、甲磺酰氯等反应制得的所谓Vilsmeier试剂等。
此反应也可以在无机或有机碱存在下进行,例如碱金属碳酸盐、碱金属碳酸氢盐、三(低级)烷基胺、吡啶、二(低级)烷氨基吡啶(如4-二甲氨基吡啶等)、N-(低级)烷基吗啉、N,N-二(低级)烷基苄胺等。
反应温度无严格要求,通常反应在从冷却到温热下进行。
起始化合物〔II〕是一种已知化合物。它可以通过在EP 0462531 A2中公开的发酵和合成方法制备。
在上述发酵过程中使用的一种鞘茎点霉F-11899的培养物已在1989年10月26日保藏在工业科学和技术署生物科学与人类技术国家研究所(前名:工业科学和技术署发酵研究所)(1-3,Higashi 1-chome,Tsukubashi,IBARAKI 305,日本),名称为FERM BP-2635。
用上述方法1得到的化合物可以用常规方法分离和纯化,例如研磨、重结晶、柱状层析、高效液体色谱(HPLC)、再沉淀等。
用以上方法1得到的化合物可以以水合物的形式得到,这种水合物包括在本发明的范围内。
应当指出,各种目标化合物(1)由于不对称碳原子和双键的存在,均可包含一种或多种立体异构体,例如旋光异构体和几何异构体,所有这些异构体及其混合物均属于本发明的范围。
本发明多肽化合物〔I〕的生物性质
为了说明本发明多肽化合物〔I〕的用途,下面解释代表性化合物的生物数据。
试验1(抗微生物活性):
后面公开的实施例17化合物的体外抗微生物活性用下述的琼脂平板两倍稀释法测定。
试验方法
将每种试验微生物在含2%葡萄糖的沙氏液体培养基中的一铂环量过夜培养物(每ml 105可见的细胞)在酵母氮基葡萄糖琼脂(YNBDA)上划线培养,琼脂中含有梯度浓度的目标多肽化合物〔I〕,最低抑制浓度(MIC)用30℃下培养24小时后的μg/ml表示
试验结果
MIC(μg/ml)
由此试验结果可见,本发明的目标多肽化合物〔I〕具有抗微生物活性(尤其是抗真菌活性)。
本发明的药物组合物可以以药物制剂的形式使用,例如固体、半固体或液体形式,制剂中含有作为活性成分的目标多肽化合物(1)或其可药用的盐,以及与之混合的一种适合直肠给药、肺部给药(经鼻或经颊吸入)、眼部给药、外用(局部)、口服、非肠道(包括皮下、静脉内和肌内)给药、吹入(包括由计量剂量的吸入器产生的气溶胶)、喷雾器或干粉吸入器的有机或无机载体或赋形剂。
活性组分可以与例如常用的可药用无毒载体混合,形成固体形式,如粒剂、片剂、糖衣剂、丸剂、锭剂、胶囊或栓剂;乳油、软膏;气溶胶,用于吹入的粉末;液体形式,如溶液、乳状液或注射用的悬浮液;食入剂;滴眼剂;以及适合使用的任何其它形式。而且如有必要,在上述制剂中可以包括辅助物质,例如稳定剂、增稠剂、润湿剂、乳化剂和着色剂、香料或缓冲剂,或通常可作为添加剂使用的任何其它物质。
目标多肽化合物〔I〕或其可药用的盐在药物组合物中的含量足以对疾病过程或症状产生所希望的抗微生物作用。
为了将组合物施用于人类,最好是以静脉内、肌内、肺部、口服或吹入的方式给药。虽然目标多肽化合物〔I〕的治疗上有效数量的剂量随要治疗的各个患者的年龄和症状而变,但一般来说,为了治疗或预防传染病,对于人静脉内给药的情形每kg体重日剂量为0.01-20mg目标多肽化合物〔I〕,在肌内用药的情形日剂量为每kg体重0.1-20mg目标多肽化合物〔I〕,在口服用药的情形日剂量为每kg体重0.5-20mg目标多肽化合物〔I〕。
尤其是在治疗或预防卡氏肺囊虫感染的情形,要注意以下事项。
对于吸入式给药,本发明化合物适合以气溶胶喷雾的形式从加压容器中作为粉末释放出出来,它可以按配方制造,而且粉末组合物可以藉助吹粉末的吸入器装置来吸入。优选用于吸入的释放体系是计量剂量的吸入式气溶胶,它可以配制成化合物在合适的喷射剂(例如碳氟化合物或碳氢化合物)中的悬浮液或溶液。
因为直接治疗肺和支气管更为理想,所以气溶胶式给药是优选的给药方法。吹入式也是一种理想的方法,特别是感染可能已经波及到耳部和其它体腔部位时。
另外,非肠道给药可以采用静脉内滴注的方法。
给出以下制备例和实施例,以便更详细地说明本发明。
制备例1
向1-(4-羟苯基)-4-叔丁氧羰基哌嗪(3g)和碳酸钾(0.82g)在N,N-二甲基甲酰胺(15ml)中的悬浮液里加入辛基溴(1.87ml)。将该混合物在70℃搅拌10小时。将反应混合物加到水和乙酸乙酯的混合物中。取出有机层,用硫酸镁干燥。滤除硫酸镁,滤液减压蒸发。残余物在硅胶上进行柱色谱,用(己烷∶乙酸乙酯=9∶1)洗脱。将含有目标化合物的级分合并,减压蒸发,得到1-(4-正辛氧基苯基)-4-叔丁氧羰基哌嗪(2.71g)。
IR(KBr):1687,1513,1241cm-1
NMR(CDCl3,δ):0.88(3H,t,J=6.2Hz),1.2-1.4
(10H,m),1.48(9H,s),1.65-1.85(2H,m),3.00
(4H,t,J=5.2Hz),3.57(4H,t,J=5.2Hz),3.90
(2H,t,J=6.5Hz),6.83(2H,dd,J=6.4和
2.1Hz),6.89(2H,dd,J=6.4和2.1Hz)
制备例2
将1-(4-正辛氧基苯基)-4-叔丁氧羰基哌嗪(2.61g)在三氟乙酸(20ml)中的溶液于环境温度下搅拌4小时。将反应混合物减压蒸发,向残余物中加入1N NaOH水溶液和乙酸乙酯的混合物。取出有机层,用硫酸镁干燥。滤除硫酸镁,滤液减压蒸发,得到1-(4-正辛氧基苯基)哌嗪(0.86g)。
IR(KBr):2923,1513,1259,831cm-1
NMR(CDCl3,δ):0.88(3H,t,J=6.4Hz),1.2-1.53
(10H,m),1.65-1.85(2H,m),3.03(4H,s),3.90
(2H,t,J=6.5Hz),6.83(2H,dd,J=6.4和
2.9Hz),6.90(2H,dd,J=6.4和 2.9Hz)APCI-MASS(大气
压化学电离-质谱:m/z=291(M++1)
制备例3
向1-(4-正辛氧基苯基)哌嗪(1g)和碳酸钾(0.476g)在N,N-二甲基甲酰胺(1ml)中的悬浮液里加入对氟苄腈(0.347g),在160℃搅拌5小时。将反应混合物加入到水和乙酸乙酯的混合物中。分出有机层,用硫酸镁干燥。滤除硫酸镁,将滤液减压蒸发,得到4-〔4-(4-正辛氧基苯基)哌嗪-1-基〕苄腈(0.93g)。
IR(KBr):2848,2217,1604,1511,1241cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.8Hz),1.2-1.53
(10H,m),1.65-1.85(2H,m),3.20(4H,t,
J=5.4Hz),3.4 8(4H,t,J=5.4Hz),3.91(2H,t,
J=6.5Hz),6.8-7.0(6H,m),7.52(2H,d,J=8.9Hz)
APCI-MASS: m/z=392(M++1)
制备例4
将2,4-二羟基苯甲醛(5.52g)、碳酸钾(6.08g)和辛基溴(7.73g)在乙腈(55ml)中的混合物在60℃搅拌16小时。减压除去反应混合物的溶剂,残余物溶在乙酸乙酯中,用水和盐水洗。分离出的有机层用硫酸镁干燥。滤除硫酸镁,将滤液减压蒸发。残余物在硅胶上进行柱色谱,用(己烷∶乙酸乙酯=9∶1)洗脱,得到2-羟基-4-辛氧基苯甲醛(6.73g)。
NMR(CDCl3,δ):0.89(3H,t,J=8.8Hz),1.2-I.5
(10H,m),1.8-2.0(2H,m),4.0-4.2(2H,m),6.42
(1H,s),6.52(1H,d,J=8.7Hz),7.79(1H,d,
J=8.7Hz),10.33(1H,s)
APCI-MASS:m/z=257(M++1)
以下化合物按照与制备4相似的方式得到。
制备例5
3,4-二戊氧基苯甲酸甲酯
NMR(CDCl3,δ):0.93(6H,t,J=6.0和9.0Hz),1.3-
2.0(12H,m),3.88(3H,s),4.04(4H,m),
6.86(1H,d,J=8.4Hz),7.53(1H,d,J=2.0Hz),
7.63(1H,dd,J=8.4和2.0Hz)
APCI-MASS:m/z=309(M++1)
制备例6
将4-溴-4’-戊基联苯(5.04g)、三甲硅烷基乙炔(2.4ml)、四(三苯膦)钯(0.96g)、三苯膦(0.22g)和碘化亚铜(95mg)在哌啶(10ml)中的混合物于氮气大气压力下在90℃加热1小时。将反应混合物倒入冷水和乙酸乙酯的混合物中,用6N盐酸调节到约pH1。分离出的有机层用水和盐水洗,用硫酸镁干燥。滤除硫酸镁,将滤液减压蒸发,得到粗制的2-〔4-(4-戊基苯基)苯基〕-1-三甲硅烷基乙炔,不经进一步纯化直接用于下一反应。将粗制的混合物溶解在二氯甲烷(10ml)和甲醇(10ml)的混合物中,在0℃向其中加入碳酸钾(2.75g)。将混合物温热至环境温度,再搅拌2小时。将反应混合物倒入冷水与乙酸乙酯的混合物中,滤除所形成的沉淀。将滤液用1N盐酸调节至约pH7,用盐水洗,用硫酸镁干燥。滤除硫酸镁,将滤液减压蒸发,得到粗制的粉末,将其在硅胶(300ml)柱色谱,用正己烷∶乙酸乙酯=99∶1-97∶3(v/v)的混合物洗脱,得到4-(4-戊基苯基)苯基乙炔(2.09g)。
IR(Nujol):3274,1490cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.4Hz),1.30-1.50
(4H,m),1.50-1.80(2H,m),2.64(2H,t,
J=7.6Hz),7.20-7.30(2H,m),7.45-7.60(6H,m)
APCI-MASS:m/z=281(M++1+MeOH)
以下化合物按照与制备例6相似的方法制得。
制备例7
6-庚氧基萘-2-基乙炔
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.20-1.60
(8H,m),1.70-1.90(2H,m),3.10(1H,s),4.07
(2H,t,J=6.5Hz),7.08(1H,d,J=2.5Hz),7.15
(1H,dd,J=2.5和8.9Hz),7.47(1H,dd,J=1.6
和8.5Hz),7.64(1H,d,J=7.3Hz),7.68(1H,d,
J=8.5Hz),7.94(1H,d,J=1.6Hz)
APCI-MASS:m/z=267(M++1)
制备例8
在-75℃向4-(4-戊基苯基)苯基乙炔(2.09g)在四氢呋喃(30ml)中的溶液里逐滴加入二异丁基氨化锂在四氢呋喃与正己烷的混合物中的溶液(1.60M,5.6ml),将所形成的混合物在-78℃搅拌1小时。向混合物中加入氯甲酸甲酯(0.72ml),令反应混合物温热至环境温度。将溶液用乙酸乙酯稀释,依次用水和盐水洗,用硫酸镁干燥。滤除硫酸镁,滤液减压蒸发,得到粗产物,将其在硅胶(150ml)柱色谱,用正己烷与乙酸乙酯的100∶0-9∶1(v/v)混合物洗脱,得到3-〔4-(4-戊基苯基)苯基〕丙酸甲酯(2.20g)。
IR(Nujol):2225,1712cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.25-1.50
(4H,m),1.52-1.80(2H,m),2.64(2H,t,
J=7.6Hz),3.85(3H,s),7.20-7.35(2H,m),7.40-
7.70(6H,m)
APCI-MASS:m/z=307(M++1)
以下化合物按照与制备例8相似的方式得到。
制备例9
3-(6-庚氧基萘-2-基)丙酸甲酯
IR(Nujol):2219,1704,1621cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.20-1.60
(8H,m),1.70-2.00(2H,m),3.86(3H,s),4.08
(2H,t,J=6.5Hz),7.10(1H,d,J=2.5Hz),7.17
(1H,dd,J=2.5和8.9Hz),7.52(1H,dd,J=1.6
和8.5Hz),7.68(1H,d,J=7.3Hz),7.72(1H,d,
J=8.5Hz),8.06(1H,d,J=1.6Hz)
APCI-MASS:m/z=325(M++1)
制备例10
将4-溴-4’-戊基联苯(5.0g)、丙烯酸甲酯(2.2ml)、乙酸钯(0.11g)和三(邻甲苯基)膦(0.60g)在三乙胺(16ml)中的混合物在氮气氛下回流15小时。将反应混合物倒入冷水和乙酸乙酯的混合物中,用6N盐酸调至约为pH1.5。分离出的有机层依次用水和盐水洗,用硫酸镁干燥。滤除硫酸镁,滤液减压蒸发,得到粗产物粉末,将其在硅胶(200ml)柱色谱,用正己烷∶乙酸乙酯=100∶0-94∶6(v/v)的混合物洗脱,得到3-〔4-(4-戊基苯基)苯基〕丙烯酸甲酯(4.48g)
IR(Nujol):1718,1637cm-1
NMR(CDCl3,δ):0.91(3H,t,J=6.7Hz),1.20-1.50
(4H,m),1.50-1.80(2H,m),2.65(2H,t,
J=7.4Hz),3.82(3H,s),6.47(1H,d,J=16.0Hz),
7.20-7.35(2H,m),7.45-7.68(6H,m),7.73(1H,
d,J=16.0Hz)
APCI-MASS:m/z=309(M++1)
以下化合物(制备例11至13)按照与制备例10相似的方式得到。
制备例11
3-(6-庚氧基萘-2-基)丙烯酸甲酯
IR(Nujol):1716,1625,1459cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.20-1.65
(8H,m),1.76-1.93(2H,m),3.82(3H,s),4.07
(2H,t,J=6.5Hz),6.49(1H,d,J=16.0Hz),7.05-
7.20(2H,m),7.55-7.90(5H,m)
APCI-MS:m/z=327(M++1)
制备例12
3-〔4-(4-庚基苯基)苯基〕丙烯酸甲酯
NMR(CDCl3,δ):0.88(3H,t,J=6.5Hz),1.15-1.50
(8H,m),1.50-1.75(2H,m),2.64(2H,t,
J=7.6Hz),3.81(3H,s),6.46(1H,d,J=16.0H2),
7.26(2H,d,J=8.2Hz),7.52(2H,d,J=8.2Hz),
7.59(6H,s),7.73(1H,d,J=16.0Hz)
APCI-MASS:m/z=337(M++1)
制备例13
3-〔4-(4-戊氧基苯基)苯基〕丙烯酸甲酯
NMR(CDCl3,δ):0.94(3H,t,J=7.0Hz),1.30-1.60
(4H,m),1.70-1.93(2H,m),3.82(3H,s),4.00
(2H,t,J=6.7Hz),6.45(1H,d,J=16.0Hz),6.90-
7.05(2H,m),7.48-8.65(6H,m),7.72(1H,d,
J=16.0Hz)
APCI-MASS:m/z=325(M++1)
制备例14
将6-庚氧基萘-2-羧酸(1.00g)和亚硫酰氯(5ml)的混合物在环境温度下搅拌18小时,减压浓缩,得到粗制的6-庚氧基-2-萘甲酰氯。向六氢异烟酸乙酯(605mg)、三乙胺(425mg)和N,N-二甲氨基吡啶(10ml)在二氯甲烷(10ml)中的混合物中加入6-庚氧基-2-萘甲酰氯粗品,将混合物在环境温度下搅拌2小时,用二氯甲烷稀释。将混合物用水、1N盐酸及盐水洗,用硫酸镁干燥。滤除硫酸镁,滤液减压蒸发。将残余物在硅胶柱色谱,用正己烷∶乙酸乙酯=3∶1的混合物洗脱,得到4-乙氧羰基-1-(6-庚氧基-2-萘甲酰)哌啶(1.20g)。
NMR(CDCl3,δ):0.90(3H,t,J=6.6Hz),1.2-2.0
(19H,m),2.5-2.7(1H,m),3.0-3.2(2H,m),4.1-
4.3(4H,m),7.1-7.2(2H,m),7.44(1H,dd,
J=8.4和1.7Hz),7.72(1H,d,J=3.9Hz),7.77
(1H,d,J=3.9Hz),7.82(1H,s)
APCI-MASS:m/z=426(M++1)
制备例15
向3,4-二氨基苯甲酸甲酯(1.91g)和三乙胺(0.56g)在N,N-二甲基甲酰胺(20ml)中的混合物里加入癸酰氯(2.31g),将混合物在0℃搅拌1小时。将反应混合物用乙酸乙酯稀释,用水和盐水洗。分离出的有机层用硫酸镁干燥,滤除硫酸镁,滤液减压蒸发。将残余物溶在甲醇(20ml)中,加入浓硫酸(0.05ml),混合物在60℃搅拌6小时。冷却后将反应混合物减压蒸发。残余物用乙酸乙酯稀释,用水和盐水洗。分离出的有机层用硫酸镁干燥。滤除硫酸镁,将滤液减压蒸发。残余物在硅胶柱色谱纯化,用(正己烷∶乙酸乙酯=3∶1)洗脱,得到5-甲氧羰基-2-壬基苯并咪唑(1.40g)。
IR(KBr压片):2923,1718,1623,1544,1438,1413,
1288,1213,1085,750cm-1
NMR(DMSO-d6,δ):0.84(3H,t,J=6.7Hz),1.1-1.4
(12H,m),1.7-1.9(2H,m),2.83(2H,t,
J=7.4Hz),7.56(1H,d,J=8.4Hz),7.78(1H,d,
J=8.4Hz),8.07(1H,s)
APCI-MASS:m/z=303(M++1)
制备例16
向丙二酸二甲酯(4ml)、2-羟基-4-辛氧基苯甲醛(2.50g)和哌啶(0.1ml)在甲醇(10ml)中的混合物里加入乙酸(0.01ml),将混合物在70℃搅拌3小时。减压去除溶剂,残余物溶在乙酸乙酯中,用0.5N盐酸、水和盐水洗,用硫酸镁干燥。滤除硫酸镁,滤液减压蒸发,过滤收集沉淀物,用正己烷洗,干燥,得到7-辛氧基香豆素-3-羧酸甲酯(0.94g)
NMR(DMSO-d6,δ):0.86(3H,m),1.2-1.6(10H,m),
1.7-1.8(2H,m),3.81(3H,s),4.11(2H,t,
J=6.4Hz),6.9-7.1(2H,m),7.83(1H,d,
J=9.0Hz),8.75(1H,s)
APCI-MASS:m/z=333(M++1)
制备例17
在环境温度下向氢化钠(423mg)和4-辛基酚(2.06g)在四氢呋喃(16ml)中的混合物里逐滴加入2-氯乙酰乙酸乙酯。将混合物在氮气氛下于70℃搅拌6小时,倒入饱和的氯化铵水溶液中。该溶液用乙酸乙酯萃取,有机层用水和盐水洗,用硫酸镁干燥。滤除硫酸镁,将滤液减压蒸发。残余物加到0℃的浓硫酸(10ml)中,将混合物搅拌10分钟。将反应混合物倒入冰水中,用1N NaOH水溶液调节至pH7.0,用乙酸乙酯萃取。有机层用水和盐水洗,用硫酸镁干燥。滤除硫酸镁,滤液减压蒸发。残余物在硅胶柱色谱,用(己烷∶乙酸乙酯=95∶5)洗脱。将含有目标化合物的级分合并,减压蒸发,得到3-甲基-5-辛基苯并〔b〕呋喃-2-羧酸乙酯(1.44g)。
IR(纯相):2925,2854,1712,1596,1463,1292,
1149,1089cm-1
NMR(CDCl3,δ):0.88(3H,t,J=6.7Hz),1.2-1.5
(10H,m),1.44(3H,t,J=7.1Hz),1.6-1.8(2H,
m),2.58(3H,s),2.71(2H,t,J=8.0Hz),4.45
(2H,t,J=7.1Hz),7.2-7.5(3H,m)
APCI-MASS:m/z=317(M++1)
制备例18
在0℃下向3-氨基-4-羟基苯甲酸乙酯(1.81g)和三乙胺(1.53ml)在二氯甲烷(20ml)中的溶液里逐滴加入癸酰氯(2.01ml)。将反应混合物在环境温度下搅拌48小时,依次用水、0.5N盐酸、水和盐水洗。分离出的有机层用硫酸镁干燥。滤除硫酸镁,将滤液减压蒸发。向溶在30ml二甲苯中的残余物里加入对甲苯磺酸一水合物(0.5g),将混合物在130℃搅拌4小时。向混合物中加乙酸乙酯,用水和盐水洗。分离出的有机层用硫酸镁干燥。滤除硫酸镁,将滤液减压蒸发。残余物在硅胶柱色谱纯化,用(正己烷∶乙酸乙酯=9∶1,v/v)洗脱,得到2-壬基苯并〔b〕噁唑-6-羧酸乙酯(2.36g)
IR(KBr压片):2914,1722,1621,1575,1470,
1429,1365,1290,1203,1151,1115,1081,
1022cm-1
NMR(CDCl3,δ):0.88(3H,t,J=6.7Hz),1.2-1.4(12H,
m),1.42(3H,t,J=7.2Hz),1.90(2H,m),2.95
(2H,t,J=7.4Hz),4.40(2H,q,J=7.0Hz),7.50
(1H,d,J=8.5Hz),8.06(1H,d,J=8.5Hz),8.37
(1H,s)
APCI-MASS:m/z=318(M++1)
制备例19
将3,4-二氨基甲酸甲酯(1.84g)和4-羟基苯甲醛(2.30g)的混合物在硝基苯(40ml)中的混合物于145℃搅拌48小时。冷却后,将混合物减压蒸发。残余物在硅胶柱色谱纯化,用(正己烷∶乙酸乙酯=2∶1)洗脱,得到5-甲氧羰基-2-(4-己氧基苯基)苯并咪唑(1.19g)。
NMR(CDCl3,δ):0.90(3H,t,J=6.4Hz),1.2-1.9(8H,
m),3.92(3H,s),3.90-4.1(2H,m),6.93(2H,d,
J=8.9Hz),7.5-7.8(1H,br),7.94(1H,dd,J=8.5
and 1.5Hz),8.03(1H,d,J=8.9Hz),8.2-8.4(1H,
br)
APCI-MASS:m/z=353(M++1)
制备例20
将3-〔4-(4-戊基苯基)苯基〕丙烯酸甲酯(2.0g)和10%钯/碳(50℃湿度,0.2g)在四氢呋喃(20ml)中的混合物在大气压力的氢气下于环境温度搅拌8小时。滤除催化剂,将滤液减压蒸发,得到3-〔4-(4-戊基苯基)苯基〕丙酸甲酯(1.93g)。
NMR(CDCl3,δ):0.90(3H,t,J=6.8Hz),1.25-1.50
(4H,m),1.50-1.75(2H,m),2.55-2.75(4H,m),
2.99(2H,t,J=8.0Hz),3.68(3H,s),7.10-7.30
(4H,m),7.40-7.60(4H,m)
APCI-MASS:m/z=311(M++1)
制备例21
将3-〔4-(4-戊氧基苯基)苯基〕丙烯酸甲酯(2.70g)和氧化铂(0.41g)在四氢呋喃(40ml)中的混合物在3大气压的氢气下于环境温度下搅拌8小时。滤除催化剂,将滤液减压蒸发,得到3-〔4-(4-戊氧基苯基)苯基〕丙酸甲酯(2.70g)。
NMR(CDCl3,δ):0.94(3H,t,J=7.0Hz),1.28-1.60
(4H,m),1.60-1.95(2H,m),2.55-2.78(2H,m),
2.98(2H,t,J=7.8Hz),3.98(2H,t,J=6.5Hz),
6.85-7.05(2H,m),7.05-7.30(2H,m),7.40-7.55
(4H,m)
APCI-MASS:m/z=327(M++1)
以下化合物按照与制备例21相似的方式得到。
制备例22
3-(6-庚氧基萘-2-基)丙酸甲酯
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.20-1.70
(8H,m),1.70-1.93(2H,m),2.70(2H,t,
J=7.7Hz),3.07·(2H,t,J=7.7Hz),3.67(3H,s),
4.05(2H,t,J=6.5Hz),7.02-7.20(2H,m),7.20-
7.38(2H,m),7.55(1H,s),7.66(1H,dd,J=3.0
和8.5Hz)
APCI-MASS:m/z=329(M++1)
制备例23
向3-〔4-(4-戊基苯基)苯基〕丙烯酸甲酯(0.41g)在四氢呋喃(5ml)中的混合物里加入3N NaOH水溶液(1.3ml),将所形成的混合物加热至85℃并保持10小时。将反应混合物倒入冷水和乙酸乙酯的混合物中,用6N盐酸调节至约pH2。分离出的有机层依次用水和盐水洗,用硫酸镁干燥。滤除硫酸镁,滤液减压蒸发,得到3-〔4-(4-戊基苯基)苯基〕丙烯酸(0.41g)。
NMR(DMSO-d6,δ):0.87(3H,t,J=7.5Hz),1.15-1.46
(4H,m),1.48-1.70(2H,m),2.61(2H,t,
J=7.4Hz),6.56(1H,d,J=16.0Hz),7.29(2H,d,
J=8.2Hz),7.60(2H,d,J=4.0Hz),7.66(2H,d,
J=4.0Hz),7.68-7.85(3H,m)
APCI-MASS:m/z=295(M++1)
以下化合物(制备例24至31)按照与制备例23相似的方式制备。
制备例24
3-〔4-(4-戊氧基苯基)苯基〕丙酸
IR(Nujol):1697,1606,1500cm-1
NMR(CDCl3,δ):0.94(3H,t,J=7.1Hz),1.25-1.60
(4H,m),1.70-1.95(2H,m),2.72(2H,t,
J=7.5Hz),3.00(2H,t,J=7.5Hz),3.99(2H,t,
J=6.5Hz),6.95(2H,dd,J=2.1和6.7Hz),7.25
(2H,d,J=8.2Hz),7.40-7.60(4H,m)
APCI-MASS:m/z=313(M++1)
制备例25
3-〔4-(4-庚基苯基)苯基〕丙酸
NMR(CDCl3,δ):0.88(3H,t,J=6.8Hz),1.15-1.50
(8H,m),1.50-1.78(2H,m),2.65(2H,t,
J=7.6Hz),6.48(1H,d,J=16.0Hz),7.27(2H,d,
J=8.2Hz),7.53(2H,d,J=8.2Hz),7.63(4H,m),
7.83(1H,d,J=16.0Hz)
APCI-MASS:m/z=323(M++1)
制备例26
3-〔4-(4-戊基苯基)苯基〕丙酸
NMR(CDCl3,δ):0.90(3H,t,J=6.4Hz),1.20-1.50
(4H,m),1.50-1.75(2H,m),2.64(2H,t,
J=8.0Hz),2.67(2H,t,J=9.6Hz),3.00(2H,t,
J=8.0Hz),7.15-7.38(4H,m),7.38-7.60(4H,m)
APCI-MASS:m/z=297(M++1)
制备例27
3-(6-庚氧基萘-2-基)丙酸
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.20-1.65
(8H,m),1.75-2.00(2H,m),2.75(2H,t,
J=7.7Hz),3.09(2H,t,J=7.7Hz),4.06(2H,t,
J=6.5Hz),7.05-7.15(2H,m),7.15-7.35(2H,m),
7.50-7.73(2H,m)
APCI-MASS:m/z=315(M++1)
制备例28
3-(6-庚氧基萘-2-基)丙烯酸
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.15-1.60
(8H,m),1.75-1.95(2H,m),4.09(2H,t,
J=6.5Hz),6.51(1H,d,J=16.0Hz),7.09-7.30(2H,
m),7.65-8.00(5H,m)
制备例29
3-〔4-(4-戊基苯基)苯基〕丙酸
NMR(CDCl3,δ):0.91(3H,t,J=6.5Hz),1.23-1.50
(4H,m),1.50-1.80(2H,m),2.65(2H,t,
J=7.6Hz),7.27(2H,d,J=8.2Hz),7.51(2H,d,
J=8.2Hz),7.58-7.80(4H,m)
APCI-MASS:m/z=325(M++1+MeOH)
制备例30
3-(6-庚氧基萘-2-基)丙酸
IR(Nujol):2645,2198,1670,1627cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.5Hz),1.10-1.60
(8H,m),1.65-1.90(2H,m),4.10(2H,t,
J=6.5Hz),7.24(1H,dd,J=2.4和8.9Hz),7.39
(1H,d,J=2.5Hz),7.55(1H,dd,J=1.6和
8.5Hz),7.8-8.0(2H,m),8.22(1H,d,J=1.6Hz)
APCI-MASS:m/z=343(M++1+MeOH)
制备例31
4-〔5-(4-戊氧基苯基)异噁唑基-3-基〕苯甲酸
IR(KBr):2939,2867,1681,1614,1429,1255,1178,
821cm-1
NMR(DMSO-d6,δ):0.91(3H,t,J=7.1Hz),1.3-1.5
(4H,m),1.6-1.8(2H,m),4.04(2H,t,J=6.5Hz),
7.11(2H,d,J=8.9Hz),7.54(1H,s),7.85(2H,
d,J=8.9Hz),7.98(2H,d,J=8.6Hz),8.11(2H,d,
J=8.6Hz)
APCI-MASS:m/z=352(M+H)+
制备例32
向3-甲基-5-辛基苯并〔b〕呋喃-2-羧酸乙酯(1.44g)在乙醇(20ml)中的溶液里加入10%NaOH水溶液(2.2ml),在环境温度下搅拌2小时,减压蒸发。残余物用1N盐酸调节至pH3.0,用乙酸乙酯萃取。有机层用盐水洗,用硫酸镁干燥。滤除硫酸镁,滤液减压蒸发,得到3-甲基-5-辛基苯并〔b〕呋喃-2-羧酸(1.00g)。
IR(KBr压片):2923,1689,1664,1581,1456,1319,
1159,933cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.7Hz),
1.2-1.5(10H,m),1.5-1.8(2H,m),2.49(3H,s),
2.69(2H,t,J=7.9Hz),7.32(1H,dd,J=8.5和
1.7Hz),7.52(1H,d,J=8.5Hz),7.54(1H,d,
J=1.7Hz),13.2-13.5(1H,br)
APCI-MASS:m/z=289(M++1)
以下化合物(制备例33至39)按照与制备例32相似的方式得到。
制备例33
3,4-二苯氧基苯甲酸
NMR(DMSO-d6,δ):0.8 9(6H,t,J=6.8Hz),
1.2-1.5(8H,m),1.6-1.8(4H,m),3.9-4.1(4H,
m),7.02(1H,d,J=8.4Hz),7.43(1H,d,
J=1.7Hz),7.53(1H,dd,J=8.4和1.7Hz)
APCI-MASS:m/z=295(M++1)
制备例34
1-(6-庚氧基-2-萘甲酰)哌啶-4-羧酸
NMR(DMSO-d6,δ):0.88(3H,t,J=6.7Hz),1.2-2.0
(14H,m),2.5-2.6(1H,m),2.9-3.2(2H,br),
3.25(2H,s),4.09(2H,t,J=6.5Hz),7.20(1H,
dd,J=8.9和2.4Hz),7.36(1H,d,J=2.3Hz),
7.43(1H,dd,J=8.4和1.5Hz),7.8-8.0(3H,m),
12.30(1H,br)
APCI-MASS:m/z=398(M++1)
制备例35
7-辛氧基香豆素-3-羧酸
IR(KBr):1748,1625,1558,1467,1430,1386,1360,
1257,1217,1120cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.8Hz),1.2-1.5
(10H,m),1.6-1.8(2H,m),4.11(2H,t,
J=6.4Hz),6.9-7.1(2H,m),7.82(1H,d,
J=8.9Hz),8.72(1H,s),12.98(1H,br)
APCI-MASS:m/z=319 (M++1)
制备例36
4-(4-戊氧基苯基)肉桂酸
IR(Nujol):2923,1675,1500,1290,1223,985,
821cm-1
NMR(DMSO-d6,δ):0.90(3H,t,J=7.0Hz),1.3-1.5
(4H,m),1.6-1.8(2H,m),4.01(2H,t,J=6.5Hz),
6.54(1H,d,J=16.0Hz),7.02(2H,d,J=8.8Hz),
7.5-7.8(7H,m)
APCI-MASS:m/z=311(M++1)
制备例37
2-壬基苯并噁唑-6-羧酸
NMR(DMSOd6,δ):0.84(3H,t,J=6.7Hz),1.2-1.5
(12H,m),1.7-1.9(2H,m),2.96(2H,t,
J=7.4Hz),7.76(1H,d,J=8.4Hz),7.98(1H,d,
J=8.4Hz),8.19(1H,s)
APCI-MASS:m/z=290(M++1)
制备例38
2-(4-己氧基苯基)苯并咪唑-5-羧酸
NMR(DMSO-d6,δ):0.8-1.0(3H,m),1.3-1.6(6H,m),
1.7-1.8(2H,m),4.06(2H,t,J=6.4Hz),7.12
(2H,d,J=8.8Hz),7.6-7.9(2H,m),8.1-8.2(3H,
m),13.00(1H,br)
APCI-MASS:m/z=339(M++1)
制备例39
2-壬基苯并咪唑-5-羧酸
NMR(DMSO-d6,δ):0.85(3H,t,J=6.7Hz),1.1-1.4
(12H,m),2.7-2.9(2H,m),2.96(2H,t,
J=7.6Hz),3.6-5.2(1H,br),7.66(1H,d,
J=8.4Hz),7.90(1H,d,J=8.4Hz),8.15(1H,s)
APCI-MASS:m/z=2 89(M++1)
制备例40
将4-〔4-(4-辛氧基苯基)哌嗪-1-基〕苄腈(0.5g)在20%H2SO4水溶液(30ml)和乙酸(20ml)中的溶液回流9小时。将反应混合物与水一起研磨。过滤收集沉淀,将其加到水、四氢呋喃和乙酸乙酯的混合物中,用1N NaOH水溶液调节至pH2.5。取出有机层,用硫酸镁干燥。滤除硫酸镁,将滤液减压蒸发,得到4-〔4-(4-辛氧基苯基)哌嗪-1-基〕苯甲酸(388mg)。
IR(KBr):2929,1664,1600,1510,1240cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.6Hz),1.2-1.5
(10H,m),1.5-1.8(2H,m),3.13(4H,t,
J=5.3Hz),3.44(4H,t,J=5.3Hz),3.88(2H,t,
J=6.5Hz),6.83(2H,d,J=9.2Hz),6.94(2H,d,
J=9.2Hz),7.02(2H,d,J=9.0Hz),7.79(2H,d,
J=9.0Hz)
APCI-MASS:m/z=411(M++1)
制备例41
向氢化钠(60%的矿物油悬浮液)(0.296g)在N,N-二甲基甲酰胺(14ml)中的悬浮液中加入1,2,4-三唑(0.511g)和4-〔4-(8-溴辛氧基)苯基〕苯甲酸(1g),在120℃搅拌5小时。将反应混合物加到水与乙酸乙酯的混合物中,用浓盐酸调节至pH2.5。取出有机层,用硫酸镁干燥。滤除硫酸镁,滤液减压蒸发,得到4-〔4-〔8-(1,2,4-三唑-1-基)辛氧基〕苯基〕苯甲酸(0.81g)。
IR(KBr):2940,1689,1604,1297,1189cm-1
NMR(DMSO-d6,δ):1.1-1.53(8H,m),1.6-1.9(4H,
m),4.00(2H,t,J=6.3Hz),4.16(2H,t,
J=7.0Hz),7.03(2H,d,J=8.7Hz),7.67(2H,d,
J=8.7Hz),7.75(2H,d,J=8.4Hz),7.95(1H,s),
7.99(2H,d,J=8.4Hz),8.51(1H,s),12.9(1H,
s)
APCI-MASS:m/z=394(M++1)
制备例42
将2-氨基甲酰-5-甲氧基苯并〔b〕噻吩(2.0g)、乙酸(5ml)和48%氢溴酸(20ml)的混合物在110℃搅拌16小时,将混合物倒入冰水中。过滤收集形成的沉淀并干燥之,得到5-羟基苯并〔b〕噻吩-2-羧酸(1.66g)。
NMR(DMSO-d6,δ):7.03(1H,dd,J=8.8和0.6Hz),
7.31(1H,d,J=0.6Hz),7.81(1H,d,J=8.8Hz),
7.96(1H,s),9.64(1H,s),13.32(1H,s)
APCI-MASS:m/z=195(M++1)
制备例43
将(S)-2-叔丁氧羰基-1,2,3,4-四氢-7-羟基异喹啉-3-羧酸(1g)在10%NaOH水溶液(2.73ml)与二甲基亚砜(11ml)的混合物中的溶液于80℃搅拌半小时。然后向其中加入辛基溴(0.589ml),在60℃搅拌4小时。将反应混合物加到水和乙酸乙酯的混合物中,用浓盐酸调节pH至2.5。分出有机层,用硫酸镁干燥。滤除硫酸镁,滤液减压蒸发,得到(S)-2-叔丁氧羰基-1,2,3,4-四氢-7-辛氧基异喹啉-3-羧酸(1.30g)。
IR(纯相):2929,1743,1704,1164cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.1Hz),1.1-1.6
(10H,m),1.41+1.51(9H,s,顺式+反式),1.75
(2H,五重峰,J=6.5Hz),3.10(2H,m),3.90(2H,t,
J=3.9Hz),4.42(1H,d,J=16.8Hz),4.65(1H,d,
J=16.8Hz),4.74+5.09(1H,m,顺式+反式),
6.5-6.8(2H,m),7.03(1H,d,J=8.3Hz)
APCI-MASS:m/z=30 6(M++1-丁氧羰基)
以下化合物(制备例44至45)按照与制备例43相似的方式得到。
制备例44
5-辛氧基苯并〔b〕噻吩-2-羧酸
IR(KBr):1673,1666,1600,1517,1409,1267,1214,
1153,865cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.7Hz),1.2-1.5
(10H,m),1.7-1.9(2H,m),4.02(2H,t,
J=6.4Hz),7.13(1H,dd,J=8.9和0.6Hz),7.51
(1H,d,J=0.6Hz),7.90(1H,d,J=9.0Hz),7.99
(1H,s)
APCI-MASS:m/z=307(M++1)
制备例45
4-〔4-(4-己氧基苯基)哌嗪-1-基〕苯甲酸二盐酸盐
IR(KBr):1668,1600,1510,1228cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.9Hz),1.2-1.5
(6H,m),1.6-1.9(2H,m),3.0-3.2(4H,m),3.3-
3.5(4H,m),3.88(2H,t,J=6.3Hz),6.83(2H,d,
J=9Hz),6.9-7.1(4H,m),7.79(2H,d,J=8.8Hz),
12.32(1H,s)
APCI-MASS:m/z=383(M+H+)
制备例46
在70℃向对苯二甲酸二甲酯(1.94g)和叔丁醇钾(2.24g)在四氢呋喃(30ml)中的悬浮液里逐滴加入在10ml四氢呋喃中的1.59g4-戊氧基苯乙酮。将混合物回流30分钟,倒入1N HCl(50ml)中。混合物用乙酸乙酯(100ml)萃取,有机层依次用水(100ml)和盐水(100ml)洗,减压蒸发。残余物与乙腈(20ml)一起研磨,过滤收集沉淀,减压干燥,得到1-(4-甲氧羰基苯基)-3-(4-戊氧基苯基)丙烷-1,3-二酮(2.41g),为黄色固体。
IR(KBr):3475,2956,2923,1720,1606,1508,1284,
1176,1108,769cm-1
NMR(CDCl3,δ):0.95(3H,t,J=7.0Hz),1.3-1.5(4H,
m),1.7-2.0(2H,m),3.96(3H,s),4.04(2H,t,
J=6.5Hz),6.82(1H,s),6.96(2H,d,J=8.9Hz),
8.0-8.1(4H,m),8.14(2H,m,J=8.7Hz),12-13
(1H,br)
APCI-MASS:m/z=369(M+H+)
制备例47
将1-(4-甲氧羰基苯基)-3-(4-戊氧基苯基)丙烷-1,3-二酮(1.00g)和盐酸羟胺(567mg)在甲醇(10ml)中的溶液回流10小时。将反应混合物用乙酸乙酯(50ml)稀释,用水(50ml×2)、盐水(50ml)洗。将有机层用硫酸镁干燥,减压去除溶剂。残余物用10ml乙腈研制,过滤收集沉淀物,减压干燥,得到4-〔5-(4-戊氧基苯基)异噁唑-3-基〕苯甲酸甲酯(0.74g)。
IR(KBr):2942,2873,1716,1616,1508,1280,
1108cm-1
NMR(CDCl3,δ):0.95(3H,t,J=6.9Hz),1.3-1.6(4H,
m),1.8-2.0(2H,m),3.95(3H,s),4.02(2H,t,
J=6.5Hz),6.74(1H,s),6.99(2H,d,J=8.8Hz),
7.76 (2H,d,J=8.8Hz),7.93(2H,d,J=8.5Hz),
8.14(2H,d,J=8.5Hz)
APCI-MASS:m/z=366(M+H)+
制备例48
将4-〔4-(8-溴代辛氧基)苯基〕苯甲酸(1g)在甲醇钠(28%甲醇溶液)(10ml)和N,N-二甲基甲酰胺(5ml)的混合物中的溶液回流5小时。将反应混合物加到水和乙酸乙酯的混合物中,用浓盐酸调节至pH2.0。分出有机层,用硫酸镁干燥。滤除硫酸镁,滤液在减压下蒸发,得到4-〔4-(8-甲氧辛氧基)苯基〕苯甲酸(0.77g)。
IR(KBr):2935,1685,835,773cm-1
NMR(CDCl3,δ):1.27-1.7(10H,m),1.7-1.95(2H,
m),3.34(3H,s),3.38(2H,t,J=6.4Hz),4.01
(2H,t,J=6.5Hz),6.99(2H,d,J=8.7Hz),7.58
(2H,d,J=8.7Hz),7.66(2H,d,J=8.4Hz),8.15
(2H,d,J=8.4Hz)
APCI-MASS:m/z=339 (M++H-H2O)
制备例49
向1-羟基苯并三唑(0.283g)和6-辛氧基甲基异烟酸(0.505g)在二氯甲烷(15ml)中的溶液里加入1-乙基-3-(3’-二甲基氨丙基)碳化二亚胺盐酸盐(WSCD·HCl)(0.473g),在环境温度下搅拌3小时。将反应混合物倒入水中。分出有机层,用硫酸镁干燥。滤除硫酸镁,滤液减压蒸发,得到1-(6-辛氧甲基异烟酰)苯并三唑3-氧化物(737mg)。
IR(纯相):1793,1654,1591,1039cm-1
以下化合物〔制备例50至66〕按照与制备例49相似的方式得到。
制备例50
1-〔4-(4-辛氧基苯基)哌嗪-1-基)苯甲酰〕-苯并三唑3-氧化物
IR(KBr):1783,1600,1511,1232,1184cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.6Hz),1.2-1.65
(10H,m),1.65-1.9(2H,m),3.24(4H,t,
J=5.3Hz),3.62(4H,t,J=5.3Hz),3.93(2H,t,
J=6.5Hz),6.8-7.1(6H,m),7.35-7.63(3H,m),
8.0-8.25(3H,m)
制备例51
1-〔4-〔4-〔8-(1,2,4-三唑-1-基)辛氧基〕苯基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1776,1600,1193,983cm-1
NMR(CDCl3,δ):1.2-2.0(12H,m),4.03(2H,t,
J=6.4Hz ),4.18(2H,t,J=7.1Hz),7.02(2H,d,
J=8.7Hz),7.4-7.63(3H,m),7.63(2H,d,
J=8.7Hz),7.79(2H,d,J=8.3Hz),7.95(1H,s),
8.06(1H,s),8.12(1H,d,J=7.7Hz),8.32(2H,
d,J=8.3Hz)
APCI-MASS:m/z=511(M++1)
制备例52
1-〔2-甲基-2-(4-辛氧苯氧基)丙酰〕苯并三唑3-氧化物
IR(纯相):2927,1810,1504,1047cm-1
制备例53
1-〔2-(4-辛氧苯氧基)丙酰〕苯并三唑3-氧化物
IR(KBr):2954,1812,1513,1232cm-1
制备例54
1-〔(S)-2-叔丁氧羰基-1,2,3,4-四氢-7-辛氧基异喹啉-3-基羰基〕苯并三唑3-氧化物
IR(纯相):2929,1816,1739,1704,1392cm-1
制备例55
丁二酰亚胺基4-(4-正辛氧基苯基)哌嗪-1-羧酸酯
IR(KBr):2925,1758,1743,1513,1241cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.8Hz),1.2-1.5
(10H,m),1.65-1.85(2H,m),2.83(4H,s),
3.0-3.2(2H,m),3.6-3.85(2H,m),3.91(2H,t,
J=6.5Hz),6.84(2H,dd,J=8.5和2.7Hz),6.90
(2H,dd,J=8.5和2.7Hz)
APCI-MASS:m/z=432(M++1)
制备例56
(6-庚氧基-2-萘基)甲基丁二酰亚胺基碳酸酯
IR(KBr):1878,1832,1787,1735,1209 cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.2Hz),1.2-1.6(8H,
m),1.73-2.0(2H,m),2.83(4H,s),4.07(2H,t,
J=6.5Hz),5.44(2H,s),7.13(1H,d,J=2.4Hz),
7.17(1H,dd,J=8.8和2.4Hz),7.44(1H,dd,
J=8.4和1.6Hz),7.67-7.85(3H,m)
制备例57
1-(3,4-二戊氧基苯甲酰)苯并三唑3-氧化物
IR(KBr):2952,1774,1594,1515,1430,1272,1147,
1089cm-1
NMR(CDCl3,δ):0.9-1.1(6H,m),1.3-1.6(8H,m),
1.8-2.1(4H,m),4.0-4.2(4H,m),6.99(1H,d,
J=8.5Hz),7.4-7.6(3H,m),7.68(2H,d,
J=2.0Hz),7.92(1H,dd,J=8.5和2.0Hz),8.10
(1H,d,J=8.5Hz)
APCI-MASS:m/z=412(M++1)
制备例58
1-(7-辛氧基香豆素-3-基羰基)苯并三唑3-氧化物
IR(KBr):2925,1754,1716,1610,1548,1282,1199,
1172,1139, 1064, 781,750cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=7.8Hz),1.2-1.5
(10H,m),1.6-1.8(2H,m),4.11(2H,t,
J=6.5Hz),6.9-7.1(2H,m),7.41(1H,t,
J=7.2Hz),7.54(1H,t,J=7.2Hz),7.72(1H,d,
J=8.3Hz),7.82(1H,d,J=8.3Hz),7.99(1H,d,
J=8.3Hz),8.72(1H,s)
APCI-MASS:m/z=436(M++1)
制备例59
1-〔4-(4-戊氧基苯基)肉桂酰〕苯并三唑3-氧化物
IR(Nujol):2854,1778,1708,1620,1597,1494,
1459,1434,1377,1350,1250,1188,1138,1086,
978cm-1
制备例60
1-(5-辛氧基苯并〔b〕噻吩-2-基羰基)苯并三唑3-氧化物
IR(KBr):2950,1776,1517,1342,1211,1151cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.7Hz),1.2-1.5
(10H,m),1.7-1.9(2H,m),4.01(2H,t,
J=6.4Hz),7.13(1H,dd,J=8.8和2.4Hz),7.42
(1H,d,J=7.1Hz),7.5-7.6(3H,m),7.72(1H,d,
J=8.4Hz),7.89(1H,d,J=8.8Hz),7.9-8.1(2H,m)
APCI-MASS:m/z=424(M++1)
制备例61
1-(3-甲基-5-辛基苯并〔b〕呋喃-2-基羰基)苯并三唑3-氧化物
IR(KBr):1776,1575,1469,1363,1324,1276,1114,
1027cm-1
NM(CDCl3,δ):0.89(3H,t,J=6.7Hz),1.2-1.5
(10H,m),2.6-2.8(2H,m),2.71(3H,s),2.76
(2H,t,J=7.4Hz),7.4-7.6(6H,m),8.12(1H,s)
APCI-MASS:m/z=406(M++I)
制备例62
1-(2-壬基苯并噁唑-5-基羰基)苯并三唑3-氧化物
IR(KBr):2980,1783,1623,1573,1276,1151,1091,
989cm-1
NMR(DMSO-d6,δ):0.84(3H,t,J=6.8Hz),1.1-1.4
(12H,m),1.81(2H,t,J=7.2Hz),2.96(3H,t,
J=7.4Hz),7.41(1H,t,J=7.0Hz),7.54(1H,t,
J=7.0Hz),7.74(2H,t,J=7.0Hz),7.98(2H,d,
J=7.0Hz),8.19(1H,s)
APCI-MASS:m/z=407(M++1)
制备例63
1-〔2-(4-己氧基苯基)苯并咪唑-5-基-羰基〕-苯并三唑3-氧化物
IR(KBr):3160,2931,2863,1778,1612,1502,1448,
1388, 1294,1247,1174,1097,1010,732cm-1
NMR(DMSO-d6,δ):0.89(3H,t,J=6.7Hz),1.2-1.5
(6H,m),1.7-1.8(2H,m),4.08(2H,t,J=6.4Hz),
7.16(2H,d,J=8.7Hz),7.6-8.4(9H,m),8.3-8.6
(1H,br)
APCI-MASS:m/z=456(M++1)
制备例64
1-〔4-〔4-(8-甲氧辛氧基)苯基〕苄氧基〕苯并三唑-3-氧化物
IR(KBr):2931,1793,1770,1600cm-1
NMR(CDCl3,δ):1.2-1.7(10H,m),1.7-1.93(2H,m),
3.34(3H,s),3.38(2H,t,J=6.4Hz),4.03(2H,
t,J=6.5Hz),7.03(2H,d,J=8.8Hz),7.4-7.7(3H,
m),7.63(2H,d,J=8.8Hz),7.79(2H,d,
J=8.6Hz),8.12(1H,d,J=8.2Hz),8.32(2H,d,
J=8.6Hz)
制备例65
1-〔4-〔4-(4-己氧基苯基)哌嗪-1-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1770,1604,1510,1232,1186cm-1
NMR(CDCl3,δ):0.91(3H,t,J=6.6Hz),1.2-1.6(6H,
m),1.6-1.9(2H,m),3.1-3.3(4H,m),3.5-3.7
(4H,m),3.93(2H,t,J=6.5Hz),6.87(2H,d,
J=9.2Hz),6.96(2H,d,J=9.2Hz),7.00(2H,d,
J=9.0Hz),7.3-7.7(3H,m),8.10(1H,d,
J=8.2Hz),8.15(2H,d,J=9.0Hz)
APCI-MASS:m/z=500(M+H+)
制备例66
1-〔4-〔5-(4-戊氧基苯基)异噁唑-3-基〕苯甲酰〕-苯并三唑3-氧化物
IR(KBr):2950,2837,1774,1616,1508,1452,1251,
1006cm-1
NMR(CDCl3,δ):0.95(3H,t,J=7.1Hz),1.3-1.5(4H,
m),1.8-2.0(2H,m),4.04(2H,t,J=6.5Hz),6.81
(1H,s),7.0-7.1(3H,m),7.4-7.6(3H,m),7.80
(2H,d,J=8.8Hz),8.0-8.2(3H,m),8.40(2H,d,
J=8.4Hz)
APCI-MASS:m/z=469(M+H)+
制备例67
向1-羟基苯并三唑(0.20g)和4-(4-戊基苯基)肉桂酸(0.40g)在二氯甲烷(12.0ml)中的悬浮液里加入1-乙基-3-(3’-二甲氨基丙基)碳化二亚胺盐酸盐(0.33g)(WSCD·HCl),将混合物在环境温度下搅拌12小时。反应混合物用二氯甲烷稀释,用盐水洗,用硫酸镁干燥。在滤除硫酸镁之后,蒸发滤液,用乙腈研制,得到1-〔4-(4-戊基苯基)肉桂酰〕苯并三唑3-氧化物(0.24g)。
NMR(CDCl3,δ):0.91(3H,t,J=6.6Hz),1.20-1.50
(4H,m),1.50-1.75(2H,m),2.66(2H,t,
J=8.0Hz),7.20-8.25(11H,m),8.55(1H,d,
J=8.4Hz)
APCI-MASS:m/z=412(M++1)
以下化合物(制备例68至73)按照与制备例67相似的方式得到。
制备例68
1-〔3-〔4-(4-戊氧基苯基)苯基〕-2-丙酰〕苯并三唑3-氧化物
NMR(CDCl3,δ):0.90-1.05(3H,m),1.30-1.65(4H,
m),1.70-1.95(2H,m),3.10-3.60(4H,m),
3.90-4.10(2H,m),6.88-7.08(2H,m),
7.20-8.50(10H,m)
APCI-MASS:m/z=430(M++1)
制备例69
1-〔4-(4-庚基苯基)肉桂酰〕苯并三唑3-氧化物
NMR(CDCl3,δ):0.89(3H,t,J=6.7Hz),1.20-1.50
(8H,m),1.50-1.80(2H,m),2.66(2H,t,
J=7.6Hz),6.70-8.60(12H,m)
APCI-MASS:m/z=440(M++1)
制备例70
1-〔3-〔4-(4-戊基苯基)苯基〕-2-丙酰〕苯并三唑3-氧化物
NMR(CDCl3,δ):0.90(3H,t,J=6.8Hz),1.20-1.50
(4H,m),1.50-1.76(2H,m),2.63(2H,t,
J=7.4Hz),3.21(2H,t,J=7.3Hz),3.51(2H,t,
J=7.3Hz),7.20-7.45(4H,m),7.45-7.70(5H,m),
7.78(1H,dt,J=1.0和7.2Hz),8.00(1H,d,
J=8.2Hz),8.42(1H,d,J=8.4Hz)
APCI-MASS:m/z=414(M++1)
制备例71
1-〔3-(6-庚氧基萘-2-基)丙酰〕苯并三唑3-氧化物
NMR(CDCl3,δ):0.80-1.10(3H,m),1.20-1.70(8H,
m),1.70-2.00(2H,m),3.10-3.70(4H,m),4.00-
4.18(2H,m),6.80-8.50(10H,m)
APCI-MASS:m/z=432(M++1)
制备例72
1-〔3-(6-庚氧基萘-2-基)丙烯酰〕苯并三唑3-氧化物
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.20-1.65
(8H,m),1.75-1.95(2H,m),4.10(2H,d,
J=6.5Hz),6.75-8.62(8H,m)
APCI-MASS:m/z=430(M++1)
制备例73
1-(4-己基苯基苯甲酰)苯并三唑3-氧化物
NMR(CDCl3,δ):0.90(3H,t,J=4.4Hz),1.2-1.5(6H,
m),1.6-1.8(2H,m),2.68(2H,t,J=8.0Hz),7.32
(2H,d,J=8.2Hz),7.4-7.7(5H,m),7.81(2H,d,
J=6.6Hz),8.10(2H,d,J=8.1Hz),8.32(2H,d,
J=7.6Hz)
APCI-MASS:m/z=400(M++1)
制备例74
向4-辛氧基苯酚(1g)在二甲基甲酰胺(10ml)和吡啶(0.364ml)中的溶液里加入N,N’-二丁二酰亚氨基碳酸酯(1.16g)。将混合物在环境温度下搅拌12小时。将反应混合物加到水和乙酸乙酯的混合物中,分出有机层,用硫酸镁干燥。滤除硫酸镁,将滤液减压蒸发,得到4-辛氧基苯基丁二酰亚胺基碳酸酯(0.59g)。
IR(KBr):2927,1876,1832,1735cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.3Hz),1.2-1.55
(10H,m),1.67-1.87(2H,m),2.87(4H,s),3.94
(2H,t,J=6.5Hz),6.89(2H,d,J=9.2Hz),7.17(2H,
d,J=9.2Hz)
APCI-MASS:m/z=364(M++1)
以下化合物(制备例75至88)按照与制备例1相似的方式得到。
制备例75
4-〔4-(6-苯基哒嗪-3-基-氧)苯基〕苯甲酸甲酯
IR(KBr):1708,1427,1280,1187,1112cm-1
NMR(CDCl3,δ):3.95(3H,s),7.2-7.7(10H,m),
7.92(1H,d,J=9.2Hz),8.0-8.2(4H,m)
APCI-MASS:m/z=383(M+H)+
制备例76
4-〔4-(5-溴代戊氧基)苯基〕苯甲酰甲酯
IR(KBr):2946,2871,1716,1602,1294,1199,1112,
837cm-1
NMR(CDCl3,δ):1.7-2.0(6H,m),3.45(2H,t,
J=6.7Hz),3.93(3H,s),4.02(2H,t,J=6.1Hz),6.97
(2H,d,J=8.7Hz),7.56(2H,d,J=8.7Hz),7.61(2H,
d,J=8.3Hz),8.07(2H,d,J=8.3Hz)
APCI-MASS:m/z=378(M+H)+
制备例77
4-〔4-(5-苯氧戊氧基)苯基〕苯甲酸甲酯
IR(KBr):2944, 2931,1720,1600,1492,1197,
1110cm-1
NMR(CDCl3,δ):1.6-1.8(2H,m),1.8-2.0(4H,m),
3.93(3H,s),4.00(2H,t,J=6.3Hz),4.04(2H,t,
J=6.3Hz),6.9-7.1(5H,m),7.3-7.4(2H,m),7.56
(2H,d,J=8.7Hz),7.62(2H,d,J=8.3Hz),8.07(2H,
d,J=8.3Hz)
APCI-MASS:m/z=391(M+H)+
制备例78
1-〔2-(4-环己基苯氨基)乙基〕-2-噁唑烷酮盐酸盐
IR(KBr):2923.6,2 852.2,1747.2,1683.6cm-1
NMR(DMSO-d6,δ):1.1-1.5(6H,m),1.6-1.9(4H,m),
2.3-2.6(1H,m),3.3-3.5(4H,m),3.58(2H,dd,
J=9.4and7.4Hz),4.22(2H,dd,J=9.4和7.4Hz),
7.1-7.4(4H,m)
制备例79
4-〔4-(8-羟基辛氧基)苯基〕苯甲酸甲酯
IR(KBr):3250,2933,2856,1724,1602,1436,1292,
1199cm-1
NMR(CDCl3,δ):1.3-1.9(12H,m),3.6-3.8(2H,br),
3.93(3H,s),4.00(2H,t,J=6.7Hz),4.82(1H,s),
7.68(2H,d,J=8.7Hz),7.56(2H,d,J=8.7Hz),7.62
(2H,d,J=8.3Hz),8.07(2H,d,J=8.3Hz)
APCI-MASS:m/z=357(M+H+)
制备例80
4-〔4-(6-溴代己氧基)苯基〕苯甲酸甲酯
IR(KBr):2937,2861,1724,1602,1529,1436,1292,
1199,1112cm-1
NMR(CDCl3,δ):1.5-2.0(8H,m),3.43(2H,t,
J=6.8Hz),3.93(3H,s),4.02(2H,t,J=6.3Hz),6.98
(2H,d,J=8.8Hz),7.56(2H,d,J=8.8Hz),7.62(2H,
d,J=8.4Hz),8.07(2H,d,J=8.4Hz)
APCI-MASS:m/z=391(M+H+)
制备例81
4-〔4-(5-溴代戊氧基)苯基〕溴苯
IR(KBr):2942,2867,1604,1515,1477,1286cm-1
NMR(CDCl3,δ):1.5-2.0(6H,m),3.44(2H,t,
J=6.7Hz),3.99(2H,t,J=6.2Hz),6.95(2H,d,
J=8.7Hz),7.3-7.6(6H,m)
APCI-MASS:m/z=399(M+H+)
制备例82
8-〔4-(4-甲氧羰基苯基)苯氧基〕辛酰哌啶
IR(KBr):2935,2852,1720,1639,1604,1438,
1292cm-1
NMR(CDCl3,δ):1.3-1.9(16H,m),2.34(2H,d,
J=7.6Hz),3.4-3.6(4H,m),3.93(3H,s),3.99(2H,
t,J=6.4Hz),6.97(2H,d,J=8.8Hz),7.55(2H,d,
J=8.8Hz),7.61(2H,d,J=8.6Hz),8.07(2H,d,
J=8.6Hz)
APCI-MASS:m/z=438(M+H+)
制备例83
6-〔4-(4-正庚氧基苯基)哌嗪-1-基〕烟酸甲酯
IR(KBr):2933,2859,1726,1608,1513,1430,
1280,1245cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.7Hz),1.2-1.8(10H,
m),3.17(4H,t,J=4.9Hz),3.8-4.0(9H,m),6.65
(1H,d,J=9.1Hz),6.86(2H,d,J=9.1Hz),6.96(2H,
d,J=9.1Hz),8.05(1H,dd,J=9.1和2.3Hz),8.82
(1H,d,J=2.3Hz)
APCI-MASS:m/z=412(M+H+)
制备例84
6-〔4-〔4-(8-溴代辛氧基)苯基〕哌嗪-1-基〕烟酸甲酯
IR(KBr):2933,2861,1724,1608,1513,1430,
1280cm-1
NMR(CDCl3,δ):1.2-2.0(12H,m),3.17(4H,t,
J=5.0Hz),3.40(2H,t,J=6.8Hz),3.8-4.0(9H,m),
6.64(1H,d,J=9.0Hz),6.85(2H,d,J=9.1Hz),6.96
(2H,d,J=9.1Hz),8.05(1H,dd,J=9.0和2.2Hz),
8.82(1H,d,J=2.2Hz)
APCI-MASS:m/z=504(M+H+)
制备例85
4-〔4-(7-溴代庚氧基)苯基〕溴苯
IR(KBr):2935.1,2856.1,1604.5cm-1
NMR(CDCl3,δ):1.18-1.65(6H,m),1.70-2.02(4H,m),
3.41(2H,t,J=6.8Hz),3.99(2H,t,J=6.4Hz),6.95
(2H,d,J=8.6Hz),7.40(2H,d,J=8.6Hz),7.46(2H,
d,J=8.6Hz),7.52(2H,d,J=8.6Hz)
制备例86
4-〔4-(8-溴代辛氧基)苯基〕溴苯
NMR(CDCl3,δ):1.22-1.65(8H,m),1.65-1.95(4H,m),
3.41(2H,t,J=6.8Hz),3.99(2H,t,J=6.4Hz),6.95
(2H,d,J=8.6Hz),7.40(2H,d,J=8.6Hz),7.46(2H,
d,J=8.6Hz),7.52(2H,d,J=8.6Hz)
制备例87
(E)-3-〔4-〔4-(5-己烯氧基)苯基〕苯基〕丙烯酸甲酯
NMR(CDCl3,δ):1.50-1.72(2H,m),1.72-1.95(2H,m),
2.05-2.14(2H,m),3.82(3H,s),4.01(2H,t,
J=6.3Hz),4.95-5.10(2H,m),5.70-5.93(1H,m),
6.46(1H,d,J=16Hz),6.97(2H,d,J=8.7Hz),7.54
(2H,d,J=8.7Hz),7.58(4H,s),7.72(1H,d,
J=16Hz)
APCI-MASS:m/z=337(M++1)
制备例88
4-溴-4’-(4-甲基戊氧基)联苯
IR(KBr):2956.3,2871.5,1606.4cm-1
NMR(CDCl3,δ):0.93(6H,d,J=6.6Hz),1.25-1.45(2H,
m),1.62(1H,sept,J=6.6Hz),1.72-1.93(2H,m),
3.98(2H,t,J=6.6Hz),6.95(2H,d,J=8.6Hz),7.30-
7.60(6H,m)
APCI-MASS:m/z=332,334(M+,M++2)
以下化合物(制备例89至90)按照与制备例2相似的方式制备。
制备例89
N-〔4-〔2-(4-甲基戊基)-2,3-二氢-4H-1,2,
4-三唑-3-酮-4-基〕苯基〕哌嗪二(三氟乙酸)盐
IR(KBr):1668.1,1519.6,1203.4,1176.4,1130.1cm-1
NMR(DMSO-d6,δ):0.86(6H,d,J=6.6Hz),1.1-1.3(2H,
m),1.4-1.8(3H,m),3.1-3.3(4H,m),3.3-3.5(4H,
m),3.70(2H,t,J=7.0Hz),7.11(2H,d,J=9.0Hz),
7.53(2H,d,J=9.0Hz),8.35(1H,s),8.90(2H,s)
制备例90
1-(4-苯基环己基)哌嗪二(三氟乙酸)盐
IR(KBr):1677.8,1197.6,1133.9cm-1
NMR(DMSO-d6,δ):1.4-1.8(4H,m),1.8-2.25(4H,m),
2.4-2.7(1H,m),3.2-3.7(9H,m),4.54(2H,br s),
7.0-7.4(5H,m),9.32(1H,br s)
APCI-MASS:m/z=245(M++H)
以下化合物(制备例91至103)按照与制备例3相似的方式得到。
制备例91
6-〔4-(4-辛氧基苯基)哌嗪-1-基〕烟酸甲酯
IR(KBr):2923,1726,1608,1515,1278,1116cm-1
NMR(CDCl3,δ):0.88(3H,t,J=6.8Hz),1.2-1.5(10H,
m),1.7-1.8(2H,m),3.1-3.2(4H,m),3.8-4.0(9H,
m),6.64(1H,d,J=9.0Hz),6.8-7.0(4H,m),8.04
(1H,dd,J=9.0和2.4Hz),8.81(1H,d,J=2.4Hz)
APCI-MASS:m/z=426(M+H+)
制备例92
4-〔4-〔4-〔2-(4-甲基戊基)-2,3-二氢-4H-1,2,4-三唑-3-酮-4-基〕苯基〕哌嗪-1-基〕苄腈
IR(KBr):2217.7,1685.5cm-1
NMR(CDCl3,δ):0.90(6H,d,J=6.6Hz),1.2-1.4(2H,
m),1.5-2.0(3H,m),3.3-3.4(4H,m),3.4-3.6(4H,
m),3.83(2H,t,J=7.4Hz),6.92(2H,d,J=9.0Hz),
7.01(2H,d,J=9.0Hz),7.43(2H,d,J=9.0Hz),7.54
(2H,d,J=9.0Hz),7.62(1H,s)
制备例93
3-氟-4-〔4-(4-甲氧苯基)哌嗪-1-基〕苄腈
IR(KBr):2225.5,1510.0,1240.0cm-1
NMR(CDCl3,δ):3.1-3.55(8H,m),3.79(3H,s),
6.7-7.1(6H,m),7.3-7.5(1H,m)
制备例94
3-氯-4-〔4-(4-正己氧基苯基)哌嗪-1-基〕苄腈
IR(KBr):2223.5,1592.9,1510.0,1490.7,1236.1cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.7Hz),1.3-1.6(6H,
m),1.7-1.9(2H,m),3.2-3.4(8H,m),3.92(2H,t,
J=6.6Hz),6.85(2H,d,J=9.3Hz),6.94(2H,d,
J=9.3Hz),7.08(1H,d,J=8.4Hz),7.53(1H,dd,
J=8.4和1.9Hz),7.64(1H,d,J=1.9Hz)
APCI-MASS:m/z=398(M++H)
制备例95
3-〔4-(4-正己氧基苯基)哌嗪-1-基〕-6-哒嗪羧酸乙酯
IR(KBr):1729.8,1587.1,1511.9,1245.8cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.2-1.4(6H,
m),1.44(3H,t,J=7.1Hz),1.65-1.85(2H,m),3.1-
3.25(4H,m),3.8-4.0(6H,m),4.46(2H,q,
J=7.1Hz),6.8-7.0(5H,m),7.91(1H,d,J=9.6Hz)
APCI-MASS:m/z=413(M++H)
制备例96
4-(4-哌啶子基哌啶-1-基)苄腈
IR(KBr):2217.7,1602.6,1511.9cm-1
NMR(CDCl3,δ):1.35-1.75(8H,m),1.92(2H,d,
J=12.9Hz),2.3-2.6(5H,m),2.86(2H,td,J=12.8
and2.6Hz),3.90(2H,d,J=12.8Hz),6.84(2H,d,
J=9.1Hz),7.46(2H,d,J=9.1Hz)
APCI-MASS:m/z=270(M++H)
制备例97
5-〔4-(4-正己氧基苯基)哌嗪-1-基〕甲基吡啶腈
IR(KBr):2223.5,1575.6,1511.9,1241.9cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.2-1.55(6H,
m),1.7-1.85(2H,m),3.22(4H,t,J=5.1Hz),3.52
(4H,t,J=5.1Hz),3.92(2H,t,J=6.5Hz),6.86(2H,
d,J=9.4Hz),6.93(2H,d,J=9.4Hz),7.13(1H,dd,
J=8.8和3.0Hz),7.53(1H,d,J=8.8Hz),8.35(1H,
d,J=3.0Hz)
APCI-MASS:m/z=365(M++H)
制备例98
4-〔4-(4-环己基苯基)哌嗪-1-基〕苄腈
IR(KBr):2219.7,1606.4,1513.8,1238.1cm-1
NMR(CDCl3,δ):1.1-1.5(6H,m),1.65-2.0(4H,m),
2.44(1H,m),3.30(4H,t,J=5.1Hz),3.46(4H,t,
J=5.1Hz),6.90(4H,d,J=8.9Hz),7.14(2H,d,
J=8.9Hz),7.52(2H,d,J=8.9Hz)
APCI-MASS:m/z=346(M++H)
制备例99
4-〔4-(4-正己基苯基)哌嗪-1-基〕苄腈
IR(KBr):2925.5,2850.3,2213.9,1604.5,1513.8,
1234.2,944.9cm-1
NMR(CDCl3,δ):0.88(3H,t,J=6.4Hz),1.2-1.45(6H,
m),1.45-1.7(2H,m),2.54(2H,t,J=7.6Hz),3.2-
3.4(4H,m),3.4-3.6(4H,m),6.89(2H,d,
J=8.5Hz),6.91(2H,d,J=8.9Hz),7.11(2H,d,
J=8.5Hz),7.52(2H,d,J=8.9Hz)
制备例100
1-〔2-(4-正己基苯氨基)乙基〕-2-噁唑烷酮盐酸盐
IR(KBr):2925.5,2852.2,1753.0,1729.8,1267.0cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.5Hz),1.1-1.4(6H,
m),1.45-1.7(2H,m),2.56(2H,t,J=7.6Hz),3.3-
3.53(4H,m),3.57(2H,t,J=7.9Hz),4.24(2H,t,
J=7.9Hz),7.24(4H,s)
APCI-MASS:m/z=291(M++H)
制备例101
4-〔4-(4-苯基环己基)哌嗪-1-基〕苄腈
IR(KBr):2212.0,1602.6,1513.8,1249.6cm-1
NMR(CDCl3,δ):1.3-1.8(4H,m),1.9-2.2(4H,m),
2.3-2.6(2H,m),2.75(4H,t,J=5.0Hz),3.34(4H,
t,J=5.0Hz),6.86(2H,d,J=8.9Hz),7.1-7.4(5H,
m),7.49(2H,d,J=8.9Hz)
APCI-MASS:m/z=346(M++H)
制备例102
6-〔4-(4-羟苯基)哌嗪-1-基〕烟酸甲酯
IR(KBr):3411,1691,1602,1510,1432,1249,
1147cm-1
NMR(DMSO-d6,δ):3.0-3.1(4H,m),3.7-3.9(7H,m),
6.67(2H,d,J=8.8Hz),6.84(2H,d,J=8.8Hz),6.93
(1H,d,J=9.1Hz), 7.97 (1H,dd,J=2.4and9.1Hz),
8.66(1H,d,J=2.4Hz),8.88(1H,s)
APCI-MASS:m/z=314(M+H)+
制备例103
1-正癸基吲哚-5-羧酸
IR(KBr):2921,2854,1679,1612,1427,1313,
1199cm-1
NMR(DMSO-d6,δ):0.84(3H,t,J=6.8Hz),1.1-1.3
(14H,m),1.6-1.8(2H,m),4.19(2H,t,J=6.9Hz),
6.57(1H,s),7.4-7.8(3H,m),8.23(1H,s),12.40
(1H,s)
APCI-MASS:m/z=302(M+H+)
以下化合物(制备例104至111)按照与制备例10相似的方式得到
制备例104
4-(4-正丁氧基苯基)肉桂酸(E)-甲酯
IR(KBr):2958,2939,2873,1720,1637,1498,1313,
1195,1170cm-1
NMR(CDCl3,δ):0.98(3H,t,J=7.3Hz),1.4-1.8(4H,
m),3.81(3H,s),4.00(2H,t,J=6.4Hz),6.45(1H,
d,J=16.0Hz),6.97(2H,d,J=8.7Hz),7.5-7.7(6H,
m),7.72(1H,d,J=16.0Hz)
APCI-MASS:m/z=311(M+H+)
制备例105
(E)-3-〔4-〔4-(4-甲基戊氧基)苯基〕苯基〕丙烯酸甲酯
IR(KBr):2956.3,2873.4,1720.2,1635.3,1600.6cm-1
NMR(CDCl3,δ):0.93(6H,d,J=6.5Hz),1.28-1.50(2H,
m),1.50-1.95(3H,m),3.82(3H,s),3.99(2H,t,
J=6.6Hz),6.44(1H,d,J=16.0Hz),6.97(2H,d,
J=8.7Hz),7.49-7.65(6H,m),7.71(1H,d,J=16Hz)
APCI-MASS:m/z=339(M++1)
制备例106
(E)-3-〔4-〔4-(6-氟代己氧基)苯基〕苯基〕丙烯酸甲酯
NMR(CDCl3,δ):1.23-2.00(8H,m),3.81(3H,s),4.01
(2H,t,J=6.4Hz),4.47(2H,dt,J=47.4和6.0Hz),
6.45(1H,d,J=16.0Hz),6.96(2H,d,J=8.8Hz),
7.45-7.63(6H,m),7.72(1H,d,J=16.0Hz)
APCI-MASS:m/z=357(M++1)
制备例107
(E)-3-〔4-〔4-(6-甲氧己氧基)苯基〕苯基〕丙烯酸甲酯
APCI-MASS:m/z=369(M+)
制备例108
(E)-3-〔4-〔4-(8-甲氧辛氧基)苯基〕苯基〕丙烯酸甲酯
IR(KBr):2935.1,2858.0,1722.1,1637.3,1602.6cm-1
NMR(CDCl3,δ):1.30-1.70(10H,m),1.70-1.92(2H,
m),3.33(3H,s),3.37(2H,t,J=6.5Hz),3.81(3H,
s),4.00(2H,t,J=6.5Hz),6.45(1H,d,J=16.0Hz),
6.97(2H,d,J=8.8Hz),7.46-7.78(6H,m),7.72(1H,
d,J=16.0Hz)
APCI-MASS:m/z=397(M+1)
制备例109
(E)-3-〔4-(4-羟苯基)苯基〕丙烯酸甲酯
IR(KBr):3409.5,1695.1cm-1
NMR(DMSO-d6,δ):3.73(3H,s),6.64(1H,d,J=16Hz),
6.85(2H,d,J=8.6Hz),7.50-7.83(5H,m)
APCI-MASS:m/z=255(M++1)
制备例110
(E)-3-〔4-〔4-(7-甲氧庚氧基)苯基〕苯基〕丙烯酸甲酯
NMR(CDCl3,δ):1.32-1.70(8H,m),1.70-1.92(2H,m),
3.34(3H,s),3.38(2H,t,J=6.4Hz),3.81(3H,s),
4.00(2H,t,J=6.5Hz),6.45(1H,d,J=16.0Hz),6.97
(2H,d,J=8.8Hz),7.47-7.65(6H,m),7.70(1H,d,
J=16Hz)
APCI-MASS:m/z=383(M++1)
制备例111
(E)-3-〔4-〔4-(7-氟代庚氧基)苯基〕苯基〕丙烯酸甲酯
IR(KBr):2937.1,2861.8,1722.1,1637.3,1600.6cm-1
以下化合物按照与制备例20相似的方式制备。
制备例112
3-〔4-(4-庚基苯基)苯基〕丙酸甲酯
NMR(CDCl3,δ):0.88(3H,t,J=6.5Hz),1.15-1.50(8H,
m),1.50-1.77(2H,m),2.52-2.73(4H,m),2.99(2H,
t,J=7.8Hz),3.68(3H,s),7.18-7.35(4H,m),7.40-
7.58(4H,m)
APCI-MASS:m/z=339(M++1)
以下化合物(制备例113至164)按照与制备例32相似的方式得到。
制备例113
4-(4-辛基苯基)-2,4-二氢-3H-1,2,4-三唑-3-酮-2-基乙酸
IR(KBr):2923.6,1704.8,1224.6cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.7Hz),1.1-1.4
(10H,m),1.4-1.7(2H,m),2.60(2H,t,J=7.2Hz),
4.38(2H,s),7.32(2H,d,J=8.5Hz),7.58(2H,d,
J=8.5Hz),8.43(IH,s)
制备例114
1-庚基-4-(4-羧基苯基)吡唑
IR(KBr):3106,2917,1687,1612,1425,1295,1184,
952,860,773cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.8Hz),1.1-1.4(8H,
m),1.7-1.9(2H,m),4.11(2H,t,J=7.0Hz),7.69
(2H,d,J=8.5Hz),7.91(2H,d,J=8.5Hz),7.98(1H,
s),8.32(1H,s),12.82(1H,br)
APCI-MASS:m/z=287(M+H+)
制备例115
6-〔4-(4-辛氧基苯基)哌嗪-1-基〕烟酸
IR(KBr压片):2919,2854,1697,1608,1515,1429,
1263,1245,1228cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.7Hz),1.1-1.5(10H,
m),1.6-1.8(2H,m),3.D-3.2(4H,m),3.7-3.9(4H,
m),3.88(2H,t,J=6.4Hz),6.7-7.0(5H,m),7.95
(1H,dd,J=9.0和1.1Hz),8.64(1H,d,J=1.1Hz)
APCI-MASS:m/z=412(M+H+)
制备例116
2-(4-己氧基苯基)苯并噁唑-5-羧酸
IR(KBr):2952,1689,1677,1619,1500,1415,1299,
1172,1024cm-1
NMR(DMSO-d6,δ):0.89(3H,t,J=6.7Hz),1.2-1.5(6H,
m),1.7-1.9(2H,m),4.09(2H,t,J=6.5Hz),7.16
(2H,d,J=8.8Hz),7.84(1H,d,J=8.5Hz),8.01(1H,
dd,J=8.5和1.5Hz),8.15(2H,d,J=8.8Hz),8.26
(1H,d,J=1.5Hz)
APCI-MASS:m/z=340(M+H+)
制备例117
4-〔4-(4-正丁氧基苯基)苯基〕苯甲酸
IR(KBr):2958,2873,1689,1600,1537,1396cm-1
制备例118
6-(4-庚氧基苯基)烟酸
IR(KBr):2858,1699,1674,1589,1425,1180,1016,
781cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.7Hz),1.2-1.5(8H,
m),1.6-1.8(2H,m),4.04(2H,t,J=6.4Hz),7.06
(2H,d,J=8.9Hz),8.03(1H,d,J=8.2Hz),8.13(2H,
d,J=8.9Hz),8.27(1H,dd,J=8.2和2.2Hz),9.09
(1H,d,J=2.2Hz),13.31(1H,br)
APCI-MASS:m/z=314(M+H+)
制备例119
5-(4-辛氧基苯基)异噁唑-3-羧酸
IR(KBr压片):2923,2852,1704,1612,1440,1272,
1178cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.8Hz),1.2-1.6
(10H,m),1.6-1.9(2H,m),4.03(2H,t,J=6.5Hz),
7.08(2H,d,J=8.9Hz),7.25(1H,s),7.86(2H,d,
J=8.9Hz)
APCI-MASS:m/z=318(M+H+)
制备例120
2-(2-辛氧基吡啶-5-基)苯并噁唑-5-羧酸
IR(KBr):2954,2923,2854,1697,1683,1625,1488,
1290cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=7.6Hz),1.2-1.5
(10H,m),1.7-1.8(2H,m),4.36(2H,t,J=6.6Hz),
7.04(1H,d,J=8.7Hz),7.88(1H, d,J=8.5Hz),8.04
(1H,dd,J=8.5和1.6Hz),8.29(1H,d,J=1.6Hz),
8.43(1H,dd,J=8.7和2.4Hz),8.99(1H,d,
J=2.4Hz),13.0-13.2(1H,br)
APCI-MASS:m/z=369(M+H+)
制备例121
2-〔4-(4-己基苯基)苯基〕苯并噁唑-5-羧酸
IR(KBr):2923,2854,1683,1411,1299,1054cm-1
APCI-MASS:m/z=400(M+H+)
制备例122
6-〔4-(4-正丁氧基苯基)苯基〕烟酸
IR(KBr):3406,2958,1691,1591,1394,1284,
1253cm-I
NMR(DMSO-d6,δ):0.94(3H,t,J=7.3Hz),1.4-1.8(4H,
m),4.01(2H,t,J=6.4Hz),7.02(2H,d,J=8.7Hz),
7.57(2H,d,J=8.7Hz),7.61(2H,d,J=8.2Hz),7.83
(2H,d,J=8.2Hz),8.05(1H,d,J=8.5Hz),8.22(1H,
dd,J=8.5and1.6Hz),9.14(1H,d,J=1.6Hz)
APCI-MASS:m/z=34 8(M+H+)
制备例123
4-〔4-(5-苯氧戊氧基)苯基〕苯甲酸
NMR(DMSO-d6,δ):1.5-1.7(2H,m),1.7-1.9(4H,m),
3.98(2H,t,J=6.3Hz),4.05(2H,t,J=6.1Hz),6.8-
7.0(3H,m),7.05(2H,d,J=8.6Hz),7.25(2H,t,
J=8.2Hz),7.68(2H,d,J=8.5Hz),7.75(2H,d,
J=8.2Hz),7.98(2H,d,J=8.2Hz),12.8-13.0(1H,br
s)
APCI-MASS:m/z=375(M-H)-
制备例124
4-〔5-(4-正己氧基苯基)-1,3,4-噁二唑-2-基〕苯甲酸
IR(KBr):2935,2854,1685,1612,1495,1425,1286,
1251cm-1
NMR(DMSO-d6,δ):0.89(3H,t,J=6.7Hz),1.2-1.5(6H,
m),1.6-1.9(3H,m),4.12(2H,t,J=6.4Hz),7.19
(2H,d,J=8.7Hz),8.08(2H,d,J=8.7Hz),8.18(2H,
d,J=8.4Hz),8.24(2H,d,J=8.4Hz)
APCI-MASS:m/z=367(M+H)+
制备例125
4-〔5-(4-正己氧基苯基)-1,3,4-噻二唑-2-基〕苯甲酸
IR(KBr):2952,2586,1699,1604,1517,1432,1251,
1174cm-1
NMR(DMSO-d6,δ):0.89(3H,t,J=6.7Hz),1.3-1.9(8H,
m),4.04(2H,t,J=6.3Hz),7.13(2H,d,J=8 .8Hz),
7.97(2H,d,J=8.8Hz),8.11(4H,s)
APCI-MASS:m/z=383(M+H)+
制备例126
5-(4-辛氧基苯基)-1-甲基吡唑-3-羧酸
IR(KBr pelet):2950,2923,1695,1450,1282,1251,
956cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.8Hz),1.2-1.5
(10H,m),1.6-1.8(2H,m),3.98(2H,t,J=6.5Hz),
4.10(3H,s),6.95(1H,d,J=8.8Hz),7.18(1H,s),
7.73(2H,d,J=8.8Hz),13.37(1H,br)
APCI-MASS:m/z=331(M+H+)
制备例127
4-〔3-(4-正戊氧基苯基)吡唑-5-基〕苯甲酸
IR(KBr):3224,2956,1692,1614,1506,1251cm-1
NMR(DMSO-d6,δ):0.91(3H,t,J=6.9Hz),1.3-1.5(4H,
m),1.6-1.8(2H,m),4.00(2H,t,J=6.5Hz),7.02
(2H,d,J=8.8Hz),7.19(1H,s),7.75(2H,d,
J=8.8Hz),7.95(2H,d,J=8.7Hz),8.02(2H,d,
J=8.7Hz),12.8-13.3(2H,br)
APCI-MASS:m/z=351(M+H+)
制备例128
5-〔4-(4-正丁氧苯基)苯基〕呋喃-2-羧酸
IR(KBr):2958,2873,1679,1487,1253,1166cm-1
NMR(DMSO-d6,δ):0.95(3H,t,J=7.3Hz),1.3-1.8(4H,
m),4.02(2H,t,J=6.3Hz),7.03(2H,d,J=8.6Hz),
7.17(1H,d,J=3.6Hz),7.33(1H,d,J=3.6Hz),7.66
(2H,d,J=8.6Hz),7.74(2H,d,J=8.4Hz),7.86(2H,
d,J=8.4Hz),13.1(1H,br s)
APCI-MASS:m/z=337(M+H)+
制备例129
3-(S)-羟基十六烷酸
IR(KBr):1679.7,1467.6,1224.6cm-1
NMR(CDCl3,δ):0.88(3H,t,J=6.4Hz),1.1-1.7(24H,
m),2.35-2.65(2H,m),4.03(1H,m),5.41(1H,br
s)
制备例130
6-〔4-(4-正己氧基苯基)哌嗪-1-基〕哒嗪-3-羧酸
IR(KBr):1697.1,1589.1,1515.8,1448.3cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.4Hz),1.2-1.5
(6H,m),1.6-1.8(2H,m),3.0-3.2(4H,m),3.7-4.0
(6H,m),6.83(2H,d,J=9.0Hz),6.95(2H,d,
J=9.0Hz),7.36(1H,d,J=9.6Hz),7.86(1H,d,
J=9.6Hz),11.68(1H,s)
制备例131
4-〔4-〔1-(4-正己氧基苯基)哌啶-4-基〕哌嗪-1-基〕苯甲酸盐酸盐
IR(KBr):1699.0,1608.3,1513.8cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.5Hz),1.2-1.5(6H,
m),1.6-1.8(2H,m),2.0-2.45(3H,m),3.2-3.8
(12H,m),3.94(2H,t,J=6.4Hz),4.03(2H,d,
J=11Hz),6.95(2H,d,J=8.7Hz),7.07(2H,d,
J=8.9Hz),7.32(2H,br s),7.83(2H,d,J=8.9Hz)
APCI-MASS:m/z=466(M++H)
制备例132
6-(8-甲氧辛氧基)-2-萘甲酸
IR(KBr):2937.1,2854.1,1677.8,1211.1cm-1
NMR(DMSO-d6,δ):1.2-1.6(10H,m),1.7-1.9(2H,m),
3.20(3H,s),3.29(2H,t,J=6.5Hz),4.11(2H,t,
J=6.4Hz),7.23(1H,dd,J=9.0和2.3Hz),7.39(1H,
d,J=2.3Hz),7.85(1H,d,J=8.7Hz),7.93(1H,d,
J=8.7Hz),7.99(1H,d,J=9.0Hz),8.51(1H,s),12.9
(1H,s)
制备例133
(E)和(Z)-3-〔4-(4-庚基苯基)苯基〕-2-丁烯酸的混合物
NMR(CDCl3,δ):0.88(3H,t,J=6.6Hz),1.15-1.50(8H,
m),1.52-1.75(2H,m),2.63和3.62(所有的3H,
均为s),2.53-2.75(2H,m),6.24和5.68(所有的
1H,均为s),7.19-7.35(2H,m),7.47-7.70(6H,m)
APCI-MASS:m/z=337(M++1),351(甲酯++1)
制备例134
3-〔4-(4-庚基苯基)苯基〕丙酸
NMR(CDCl3,δ):0.88(3H,t,J=6.6Hz),1.13-1.48(8H,
m),1.48-1.75(2H,m),2.52-2.83(4H,m),3.00(2H,
t,J=7.8Hz),7.15-7.35(4H,m),7.40-7.60(4H,m)
APCI-MASS:m/z=323(M+-1)
制备例135
4-(4-正庚基苯基)苯甲酰-羧酸
NMR(CDCl3,δ):0.88(3H,t,J=6.6Hz),1.13-1.50(8H,
m),1.50-1.75(2H,m),2.66(2H,t,J=7.7Hz),7.20-
7.40(2H,m),7.50-7.66(2H,m),7.66-7.84(2H,m),
8.40-8.60(2H,m)
APCI-MASS:m/z=323(M+-1)
制备例136
6-己基萘-2-羧酸
NMR(CDCl3,δ):0.89(3H,t,J=6.8Hz),1.15-1.53(6H,
m),1.55-1.84(2H,m),2.80(2H,t,J=7.6Hz),7.42
(1H,dd,J=1.7和8.4Hz),7.67(1H,s),7.84(1H,
d,J=8.6Hz),7.90(1H,d,J=8.4Hz),8.09(1H,dd,
J=1.7和8.6Hz),8.68(1H,5)
APCI-MASS:m/z=257(M++1),271(甲酯++1)
制备例137
3-(E)-〔4-〔4-(7-甲氧庚氧基)苯基〕苯基〕丙烯酸
NMR(DMSO-d6,δ):1.20-1.60(8H,m),1.60-1.83(2H,
m),3.21(3H,s),3.25-3.60(2H,m),4.01(2H,t,
J=6.4Hz),6.54(1H,d,J=16.0Hz),7.02(2H,d,
J=8.8Hz),7.55-7.80(7H,m)
APCI-MASS:m/z=369(M++1)
制备例138
3-(E)-〔4-〔4-(8-甲氧辛氧基)苯基〕苯基〕丙烯酸
IR(KBr):3037.3,2933.2,2858.0,2551.4,1706.7,
1677.8,1629.6,1602.6cm-1
NMR(DMSO-d6,δ):1.18-1.55(10H,m),1.65-1.83(2H,
m),3.18-3.45(5H,m),4.01(2H,t,J=6.5Hz),6.53
(1H,d,J=16.0Hz),7.02(2H,d,J=8.8Hz),7.50-8.80
(7H,m)
APCI-MASS:m/z=383(M++1)
制备例139
3-(E)-〔4-〔4-(5-己烯氧基)苯基〕苯基〕丙烯酸
NMR(DMSO-d6,δ):1.42-1.63(2H,m),1.63-1.85(2H,
m),2.00-2.20(2H,m),4.03(2H,t,J=6.3Hz),4.90-
5.15(2H,m),5.68-5.97(1H,m),6.54(1H,d,
J=16Hz),7.02(2H,d,J=8.7Hz),7.50-7.80(7H,m)
APCI-MASS:m/z=323(M++1)
制备例140
3-(E)-〔4-〔4-(4-甲基戊氧基)苯基〕苯基〕丙烯酸
IR(KBr):2956.3,2869.6,2713.4,2599.6,1689.3,
1627.6,1602.6cm-1
NMR(DMSO-d6,δ):0.89(6H,d,J=6.5Hz),1.15-1.43
(2H,m),1.48-1.90(3H,m),4.00(2H,t,J=6.7Hz),
6.54(1H,d,J=16Hz),7.02(2H,d,J=8.7Hz),7.50-
7.90(7H,m)
APCI-MASS:m/z=325(M++1)
制备例141
3-(E)-〔4-〔4-(6-氟代己氧基)苯基〕苯基〕丙烯酸
NMR(CDCl3,δ):1.39-2.00(8H,m),4.01(2H,t,
J=6.5Hz),4.47(2H,dt,J=47.3and6.0Hz),6.49
(1H,d,J=15.9Hz),6.98(2H,d,J=8.7Hz),7.40-7.70
(6H,m),7.81(1H,d,J=15.9Hz)
APCI-MASS:m/z=343(M++1)
制备例142
3-(E)-〔4-〔4-(6-甲氧己氧基)苯基〕苯基〕丙烯酸
NMR(DMSO-d6,δ):1.22-1.63(6H,m),1.63-1.88(2H,
m),3.21(3H,s),3.22-3.40(2H,m),4.00(2H,t,
J=6.5Hz),6.54(1H,d,J=15.8Hz),7.02(2H,d,
J=8.7Hz),7.50-7.84(7H,m)
APCI-MASS:m/z=369(甲酯,M++1)
制备例143
4-〔4-〔8-(四氢吡喃-2-基-氧)辛氧基〕苯基〕苯甲酸
IR(KBr):2935,1697,1683,1604,1303,1290,
1197cm-1
NMR(DMSO-d6,δ):1.2-1.8(18H,m),3.3-3.9(4H,m),
4.01(2H,t,J=6.3Hz),4.5-4.6(1H,m),7.03(2H,
d,J=8.7Hz),7.67(2H,d,J=8.7Hz),7.74(2H,d,
J=8.3Hz),7.98(2H,d,J=8.3Hz)
APCI-MASS:m/z=425(M-H+)
制备例144
4-〔3-(4-正己氧基苯基)吡唑-5-基〕苯甲酸
IR(KBr):2956,2935,1693,1614,1508,1432,1251,
1178cm-1
NMR(DMSO-d6,δ):0.89(3H,t,J=6.4Hz),1.2-1.5(6H,
m),1.6-1.8(2H,m),4.00(2H,t,J=6.4Hz),7.02
(2H,d,J=8.7Hz),7.12(1H,s),7.74(2H,d,
J=8.7Hz),7.95(2H,d,J=8.8Hz),8.01(2H,d,
J=8.8Hz),13.17(1H,s)
APCI-MASS:m/z=365(M+H+)
制备例145
4-〔4-〔4-(6-甲氧己氧基)苯基〕苯基〕苯甲酸
IR(KBr):2939,2861,1685,1602,1430,1286,
1128cm-1
NMR(DMSO-d6,δ):1.3-1.8(8H,m),3.21(3H,s),
3.3-3.4(2H,m),4.01(2H,t,J=6.5Hz),7.04(2H,
d,J=8.6Hz),7.66(2H,d,J=8.6Hz),7.7-7.9(6H,
m),8.03(2H,d,J=8.2Hz)
APCI-MASS:m/z=405(M+H+)
制备例146
4-〔5-〔4-(8-甲氧辛氧基)苯基〕-1,3,4-噻二唑-2-基〕苯甲酸
IR(KBr):2931,2854,1691,1602,1251cm-1
NMR(DMSO-d6,δ):1.2-2.0(12H,m),3.20(3H,s),
3.29(2H,t,J=6.4Hz),4.04(2H,t,J=6.4Hz),7.13
(2H,t,J=8.8Hz),7.9-8.2(6H,m),13.95(1H,br)
APCI-MASS:m/z=4 41(M+H+)
制备例147
4-(4-正丁氧基苯基)肉桂酸
IR(KBr):2958,2871,1695,1625,1498,1249cm-1
NMR(DMSO-d6,δ):0.94(3H,t,J=7.3Hz),1.44(2H,
tq,J=7.0和7.3Hz),1.71(2H,tt,J=7.0和
6.4Hz),4.01(2H,t,J=6.4Hz),6.54(1H,d,
J=16.0Hz),7.02(2H,d,J=8.7Hz),7.6-7.9(7H,m)
APCI-MASS:m/z=297(M+H+)
制备例148
4-〔5-(4-环己基苯基)-1,3,4-噻二唑-2-基〕苯甲酸
IR(KBr):2925,2850,1683,1429,1292cm-1
NMR(DMSO-d6,δ):1.1-1.5(5H,m),1.6-2.0(5H,m),
2.4-2.6(1H,m),7.45(2H,d,J=8.3Hz),7.96(2H,
d,J=8.3Hz),8.13(4H,5)
APCI-MASS:m/z=365(M+H)+
制备例149
4-〔5-〔4-(哌啶-1-基)苯基〕-1,3,4-噻二唑-2-基〕苯甲酸
IR(KBr):2931,2854,1685,1604,1415,1238cm-1
NMR(DMSO-d6,δ):1.61(6H,s),3.31(4H,s),7.05
(2H,d,J=9.0Hz),7.83(2H,d,J=9.0Hz),8.10(4H,
s)
APCI-MASS:m/z=366(M+H)+
制备例150
4-〔5-〔4-(4-正丙氧基苯基)苯基〕-1,3,4-噁二唑-2-基〕苯甲酸
IR(KBr):2939,1689,1606,1488,1429,1290cm-1
NMR(DMSO-d6,δ):1.00(3H,t,J=7.3Hz),1.76(2H,
tq,J=6.5和7.3Hz),4.00(2H,t,J=6.5Hz),7.07
(2H,d,J=8.8Hz),7.70(2H,d,J=8.5Hz),7.78(2H,
d,J=8.8Hz),7.90(2H,d,J=8.5Hz),8.0-8.4(4H,m)
APCI-MASS:m/z=401(M+H)+
制备例151
4-(5-正壬基-1,3,4-噁二唑-2-基)苯甲酸
IR(KBr):2919,2852,1685,1565,1430,1284cm-1
NMR(DMSO-d6,δ):0.84(3H,t,J=6.5Hz),1.2-1.5
(12H,m),1.7-1.9(2H,m),2.94(2H,t,J=7.4Hz),
8.0-8.2(4H,m),13.35(1H,s)
APCI-MASS:m/z=317(M+H+)
制备例152
4-〔3-(4-正己氧基苯基)-1,2,4-噁二唑-5-基〕苯甲酸
IR(KBr):2942,2869,1695,1421,1251cm-1
NMR(DMSO-d6,δ):0.89(3H,t,J=6.8Hz),1.2-1.8(8H,
m),4.06(2H,t,J=6.5Hz),7.13(2H,d,J=8.9Hz),
8.03(2H,d,J=8.9Hz),8.17(2H,d,J=8.5Hz),8.28
(2H,d,J=8.5Hz)
APCI-MASS:m/z=367(M+H)+
制备例153
4-〔4-〔4-(5-甲氧戊氧基)苯基〕苯基〕苯基乙酸
IR(KBr):2939,2861,1699,1253,1182,1124cm-1
NMR(DMSO-d6,δ):1.4-1.9(6H,m),3.22(3H,s),3.39
(2H,t,J=6.2Hz),3.61(2H,s),4.01(2H,t,
J=6.4Hz),7.02(2H,d,J=8.8Hz),7.35(2H,d,
J=8.2Hz),7.6-7.8(8H,m)
APCI-MASS:m/z=405(M+H+)
制备例154
4-〔5-(4-正辛氧基苯基)-1,3,4-噻二唑-2-基〕苯甲酸
IR(KBr):2921,2856,1691,1432,1251cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.7Hz),1.2-1.5
(10H,m),1.7-1.9(2H,m),4.07(2H,t,J=6.5Hz),
7.13(2H,d,J=8.9Hz),7.97(2H,d,J=8.9Hz),8.12
(4H,s)
APCI-MASS:m/z=411(M+H+)
制备例155
4-〔5-(4-正戊基环己基)-1,3,4-噻二唑-2-基〕苯甲酸
IR(KBr):2919,2848,1677,1430,1294cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.9Hz),1.0-1.4
(11H,m),1.5-1.6(2H,m),1.8-2.0(2H,m),2.1-2.3
(2H,m),3.1-3.3(1H,m),8.07(4H,s)
APCI-MASS:m/z=359(M+H+)
制备例156
4-〔3-(4-正戊氧基苯基)异噁唑-5-基〕苯甲酸
IR(KBr):2925,2869,1699,1687,1612,1432,1251,
1178cmu
NMR(DMSO-d6,δ):0.91(3H,t,J=6.9Hz),1.2-1.5(4H,
m),1.7-1.9(2H,m),4.04(2H,t,J=6.5Hz),7.09
(2H,d,J=8.8Hz),7.69(1H,s),7.85(2H,d,
J=8.8Hz),8.01(2H,d,J=8.5Hz),8.11(2H,d,
J=8.5Hz)
APCI-MASS:m/z=352(M+H+)
制备例157
4-〔5-〔4-(8-甲氧辛氧基)苯基〕-1,3,4-噁二唑-2-基〕苯甲酸
IR(KBr):2967,2937,2877,1687,1290cm-1
NMR(DMSO-d6,δ):1.2-1.6(10H,m),1.7-1.9(2H,m),
3.20(3H,s),3.29(2H,t,J=6.4Hz),4.08(2H,t,
J=6.5Hz),7.17(2H,d,J=8.9Hz),8.07(2H,d,
J=8.9Hz),8.15(2H,d,J=8.6Hz),8.24(2H,d,
J=8.6Hz)
APCI-MASS:m/z=425(M+H)+
制备例158
4-〔4-(6-苯基哒嗪-3-基-氧)苯基〕苯甲酸
IR(KBr):1700,1687,1608,1427,1284,1186cm-1
NMR(DMSO-d6,δ):7.40(2H,d,J=8.6Hz),7.5-7.7(4H,
m),7.7-7.9(4H,m),7.9-8.1(4H,m),8.35(1H,d,
J=9.2Hz),12.99(1H,br s)
APCI-MASS:m/z=369(M+H)+
制备例159
4-〔5-(4-正辛氧基苯基)-1,3,4-噁二唑-2-基〕苯甲酸
IR(KBr):2921,2852,1685,1612,1496,1425,1288,
1251cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.7Hz),1.2-1.5
(10H,m),1.7-1.9(2H,m),4.08(2H,t,J=6.4Hz),
7.17(2H,d,J=8.7Hz),8.07(2H,d,J=8.7Hz),8.15
(2H,d,J=8.5Hz),8.24(2H,d,J=8.5Hz),13.36(1H,
br)
APCI-MASS:m/z=395(M+H+)
制备例160
4-〔2-(4-正己氧基苯基)嘧啶-6-基〕苯甲酸
IR(KBr):2944,2863,1697,1585,1415,1386,
1253cm-1
NMR(DMSO-d6,δ):0.89(3H,t,J=6.7Hz),1.2-1.6(6H,
m),1.7-1.9(2H,m),4.07(2H,t,J=6.6Hz),7.10
(2H,d,J=8.9Hz), 8.00(1H,d,J=5.2Hz),8.13(2H,
d,J=8.4Hz),8.44(2H,d,J=5.9Hz),8.47(2H,d,
J=5.9Hz),8.95(1H,d,J=5.2Hz)
APCI-MASS:m/z=377(M+H+)
制备例161
4-〔4-(7-哌啶羰基庚氧基)苯基〕苯甲酸
IR(KBr):2933,2858,1697,1677,1637,1604,1429,
1249cm-1
NMR(DMSO-d6,δ):1.2-1.8(16H,m),2.26(2H,t,
J=7.5Hz),3.2-3.5(4H,m),4.01(2H, t,J=6.4Hz),
7.03(2H,d,J=8.8Hz),7.67(2H,d,J=8.8Hz),7.74
(2H,d,J=8.4Hz),7.98(2H,d,J=8.4Hz)
APCI-MASS:m/z=424(M+H+)
制备例162
6-〔4-(4-正庚氧基苯基)哌嗪-1-基〕烟酸
IR(KBr):2929,2854,1695,1673,1606,1577,1515,
1421,1245cm-1
NMR(DMSO-d6,δ):D.86(3H,t,J=6.7Hz),1.2-1.5(8H,
m),1.6-1.8 2H,m),3.0-3.2(4H,m),3.6-3.8(4H,
m),3.87(2H,t,J=6.5Hz),6.8-7.2(5H,m),7.95
(1H,dd,J=8.9and2.3Hz),8.26(1H,d,J=2.3Hz)
APCI-MASS:m/z=398(M+H+)
制备例163
6-〔4-〔4-(8-甲氧辛氧基)苯基〕哌嗪-1-基〕烟酸
IR(KBr):2933,2856,1697,1672,1605,1511,1421,
1245cm-1
NMR(DMSO-d6,δ):1.2-1.8(12H,m),3.08(4H,t,
J=5.0Hz),3.20(3H,s),3.28(2H,t,J=6.5Hz),3.78
(4H,t,J=4.6Hz),3.8 7(2H,t,J=6.4Hz),6.8-7.0
(5H,m),7.95(1H,dd,J=9.0和2.2Hz),8.65(1H,
d,J=2.2Hz),12.54(1H,s)
APCI-MASS:m/z=442(M+H+)
制备例164
4-〔5-〔4-(4-正丙氧基苯基)苯基〕-1,3,4-噻二唑-2-基〕苯甲酸
IR(KBr):1685,1537,1423,817cm-1
NMR(DMSO-d6,δ):1.00(3H,t,J=6.7Hz),1.6-1.8(2H,
m),4.00(2H,t,J=6.6Hz),7.0-7.2(2H,d,
J=8.6Hz),7.6-8.1(10H,m)
APCI-MASS:m/z=417(M+H)+
制备例165
在80℃向4-〔5-(4-正戊氧基苯基)异噁唑-3-基〕苯甲酸乙酯(6.33g)的乙醇(60ml)溶液四氢呋喃(90ml)中加入2N NaOH水溶液(12.5ml)。将混合物回流1小时,倒入冰水中。将悬浮液用1N HCl调节至pH2.0。过滤收集沉淀,用水洗,干燥,得到5.80g)4-〔5-(4-正戊氧基苯基)异噁唑-3-基〕苯甲酸。
IR(KBr):2939,2867,1681,1614,1429,1255,1178,
821cm-1
NMR(DMSO-d6,δ):0.91(3H,t,J=7.1Hz),1.3-1.5(4H,
m),1.6-1.8(2H,m),4.04(2H,t,J=6.5Hz),7.11
(2H,d,J=8.9Hz),7.54(1H,s),7.85(2H,d,
J=8.9Hz),7.98(2H,d,J=8.6Hz),8.11(2H,d,
J=8.6Hz)
APCI-MASS:m/z=352(M+H)+
以下化合物(制备例166至170)按照与制备例40相似的方式得到。
制备例166
5-〔4-(4-正己氧基苯基)哌嗪-1-基〕吡啶甲酸三盐酸盐
IR(KBr):1689.3,1577.5,1511.9,1241.9cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.5Hz),1.15-1.5
(6H,m),1.6-1.8(2H,m),3.1-3.25(4H,m),3.45-
3.6(4H,m),3.89(2H,t,J=6.4Hz),6.84(2H,d,
J=9.1Hz),6.97(2H,d,J=9.1Hz),7.43(1H,dd,
J=8.8和3.0Hz),7.90(1H,dd,J=8.8和0.7Hz),
8.41(1H,dd,J=3.0和0.7Hz)
APCI-MASS:m/z=384(M++H)
制备例167
4-〔4-(4-苯基环己基)哌嗪-1-基〕苯甲酸二盐酸盐
IR(KBr):1700.9,1606.4,1220.7,1180.2cm-1
NMR(DMSO-d6,δ):1.4-1.85(4H,m),1.9-2.05(2H,m),
2.2-2.4(2H,m),3.1-3.5(6H,m),3.5-3.7(2H,m),
3.9-4.2(2H,m),7.06(2H,d,J=8.8Hz),7.1-7.4
(5H,m),7.83(2H,d,J=8.8Hz)
APCI-MASS:m/z=365(M++H)
制备例168
4-(4-反-正戊基环己基)苯甲酸
IR(KBr):1681.6,1423.2,1290.1cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.6Hz),1.0-1.6(13H,
m),1.89(4H,d,J=10Hz),2.54(1H,t,J=12Hz),
7.30(2H,d,J=8.3Hz),8.03(2H,d,J=8.3Hz)
APCI-MASS:m/z=274(M++H)
制备例169
4-(4-哌啶子基哌啶-1-基)苯甲酸
IR(KBr):1710.6,1403.9cm-1
NMR(DMSO-d6,δ):1.6-2.1(8H,m),2.17(2H,d,
J=12Hz),2.7-3.05(4H,m),3.2-3.5(1H,m),3.35
(2H,d,J=12Hz),4.05(2H,d,J=13Hz),7.01(2H,d,
J=8.9Hz),7.77(2H,d,J=8.9Hz),10.84(1H,s)
APCI-MASS:m/z=289(M++H)
制备例170
3-氯-4-〔4-(4-正己氧基苯基)哌嗪-1-基〕苯甲酸二盐酸盐
IR(KBr):1712.5,1598.7,1513.8,1251.6cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.6Hz),1.2-1.5(6H,
m),1.6-1.8(2H,m),3.4-3.6(8H,m),3.98(2H,t,
J=6.4Hz),7.02(2H,d,J=9.0Hz),7.32(1H,d,
J=8.1Hz),7.60(2H,d,J=9.0Hz),7.89(1H,d,
J=8.1Hz),8.02(1H,s)
APCI-MASS:m/z=417(M++H)
以下化合物(制备例171至175)按照与制备例41相似的方式制备。
制备例171
〔4-(4-辛基苯基)-2,3-二氢-4H-1,2,4-三唑-3-酮-2-基〕乙酸乙酯
IR(KBr):2921.6,1764.5,1715,1197.6cm-1
NMR(CDCl3,δ):0.88(3H,t,J=6.7Hz),1.30(3H,t,
J=7.1Hz),1.2-1.4(10H,m),1.5-1.7(2H,m),2.63
(2H,t,J=7.9Hz),4.26(2H,q,J=7.1Hz),4.64(2H,
s),7.28(2H,d,J=8.4Hz),7.44(2H,d,J=8.4Hz),
7.71(1H,s)
制备例172
4-〔4-(4-叔丁氧羰基哌嗪-1-基)苯基〕-2-(4-甲基戊基)-2,3-二氢-4H-1,2,4-三唑-3-酮
IR(KBr):1687.4cm-1
(CDCl3,δ):0.90(6H,d,J=6.5Hz),1.1-1.4(2H,
m),1.49(9H,s),1.4-1.9(3H,m),3.16(4H,t,
J=4.9Hz),3.59(4H,t,J=4.9Hz),3.82(2H,t,
J=7.3Hz),6.98(2H,d,J=9.0Hz),7.41(2H,d,
J=9.0Hz),7.61(1H,s)
制备例173
6-(8-溴代辛氧基)-2-萘甲酸甲酯
IR(KBr):2933.2,2856.1,1720.2,1294,1209.1cm-1
NMR(CDCl3,δ):1.3-1.6(8H,m),1.75-2.0(4H,m),
3.42(2H,t,J=6.8Hz),3.96(3H,s),4.09(2H,t,
J=6.5Hz),7.14(1H,d,J=1.7Hz),7.19(1H,dd,
J=8.9和1.7Hz),7.73(1H,d,J=8.7Hz),7.83(1H,
d,J=8.9Hz),8.01(1H,dd,J=8.7和1.7Hz),8.51
(1H,d,J=1.7Hz)
APCI-MASS:m/z=393(M++H)
制备例174
4-〔4-(6-正丙氧己氧基)苯基〕苯甲酸
IR(KBr):2937,2858,1695,1683,1604,1430,1290,
1247,1195cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=7.4Hz),1.3-1.9
(10H,m),3.2-3.4(4H,m),4.01(2H,t,J=6.3Hz),
7.04(2H,d,J=8.7Hz),7.67(2H,d,J=8.7Hz),7.74
(2H,d,J=8.3H2),7.98(2H,d,J=8.3Hz),12.9(1H,
s)
APCI-MASS:m/z=357(M+H+)
制备例175
4-〔4-(6-溴代己氧基)苯基〕溴苯
NMR(CDCl3,δ):1.40-1.65(4H,m),1.70-2.00(4H,m),
3.43(2H,t,J=6.7Hz),4.00(2H,t,J=6.4Hz),6.95
(2H,d,J=8.8Hz),7.30-7.60(6H,m)
以下化合物(制备例176至180)按照与制备例43相似的方式得到。
制备例176
4-〔4-(4-正戊氧基苯基)哌嗪-1-基〕苯甲酸二盐酸盐
IR(KBr):1668.1,1602.6,1510.0,1228.4cm-1
NMR(DMSO-d6,δ):0.89(3H,t,J=6.9Hz),1.2-1.5(5H,
m),1.6-1.9(2H,m),3.0-3.2(4H,m),3.4-3.6(4H,
m),3.88(2H,t,J=6.4Hz),6.83(2H,d,J=9Hz),
6.9-7.1(4H,m),7.79(2H,d,J=8.8Hz),12.32(1H,
s)
APCI-MASS:m/z=369(M+H+)
制备例177
4-〔4-(4-正庚氧基苯基)哌嗪-1-基〕苯甲酸二盐酸盐
IR(KBr):1666.2,1600.6,1511.9cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.9Hz),1.2-2.0(10H,
m),3.1-3.3(4H,m),3.4-3.6(4H,m),3.92(2H,t,
J=6.4Hz),6.8-7.1(6H,m),8.00(2H,d,J=8.8Hz)
制备例178
4-〔4-〔4-(4-甲基戊氧基)苯基〕哌嗪-1-基〕苯甲酸二盐酸盐
IR(KBr):1668.1,1602.6,1510.0,1236.1cm-1
NMR(DMSO-d6,δ):0.89(6H,d,J=6.5Hz),1.2-1.4(2H,
m),1.4-1.8(3H,m),3.0-3.2(4H,m),3.3-3.5(4H,
m),3.87(2H,t,J=6.3Hz),6.83(2H,d,J=9.0Hz),
6.9-7.1(4H,m),7.79(2H,d,J=8.8Hz),12.33(1H,
s)
APCI-MASS:m/z=383(M+H+)
制备例179
4-〔4-〔4-(8-溴代辛氧基)苯基〕哌嗪-1-基〕苯甲酸二盐酸盐
IR(KBr):1670.1,1602.6,1511.9,1234.2cm-1
NMR(DMSO-d6,δ):1.2-1.5(8H,m),1.6-1.9(4H,m),
3.0-3.2(4H,m),3.2-3.5(4H,m),3.52(2H,t,
J=6.7Hz),3.88(2H,t,J=6.4Hz),6.83(2H,d,
J=9.1Hz),6.94(2H,d,J=9.1Hz),7.02(2H,d,
J=8.9Hz),7.79(2H,d,J=8.9Hz)
制备例180
3-氟-4-〔4-(4-正己氧基苯基)哌嗪-1-基〕苯甲酸二盐酸盐
IR(KBr):1673.9,1511.9,1240.0cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.5Hz),1.2-1.5(6H,
m),1.6-1.8(2H,m),3.0-3.5(8H,m),3.88(2Ht,
J=6.4Hz),6.7-7.2(5H,m),7.4-7.8(2H,m),12.82
(1H,s)
APCI-MASS:m/z=401(M++H)
以下化合物按照与制备例46相似的方式得到。
制备例181
1-(4-甲氧羰基苯基)-3-(4-正己氧基苯基)丙-1,3-二酮
IR(KBr):2956,2927,2856,1722,1511,1284,
1108cm-1
NMR(CDCl3,δ):0.92(3H,t,J=6.4Hz),1.2-2.0(8H,
m),3.96(3H,s),4.04(2H,t,J=6.5Hz),6.82(1H,
s),6.97(2H,d,J=8.7Hz),7.9-8.1(4H,m),8.14
(2H,d,J=8.3Hz)
APCI-MASS:m/z=383(M+H+)
以下化合物(制备例182至185)按照与制备例47相似的方式得到、
制备例182
5-(4-辛氧基苯基)-1-甲基吡唑-3-羧酸甲酯
IR(KBr压片):2923,1724,1616,1513,1446,1251,
1120cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.8Hz),1.2-1.5(10H,
m),1.7-1.9(2H,m),3.90(3H,s),3.98(2H,t,
J=6.6Hz),4.20(3H,s),6.92(2H,d,J=8.9Hz),7.04
(1H,s),7.89(2H,d,J=8.9Hz)
APCI-MASS:m/z=345(M+H+)
制备例183
4-〔5-(4-正戊氧基苯基)吡唑-3-基〕苯甲酸甲酯
IR(KBr):3236,2952,2873,1716,1616,1508,1276,
1174,1106cm-1
NMR(CDCl3,δ):0.94(3H,t,J=7.0Hz),1.3-1.5(4H,
m),1.7-1.9(2H,m),3.92(3H,s),3.96(2H,t,
J=6.7Hz),6.78(1H,s),6.88(2H,d,J=8.7Hz),7.55
(2H,d,J=8.7Hz),7.79(2H,d,J=8.4Hz),8.02(2H,
d,J=8.4Hz)
APCI-MASS:m/z=365(M+H+)
制备例184
5-(4-辛氧基苯基)异噁唑-3-羧酸甲酯
IR(KBr压片):2950,2921,1724,1614,1510,1446,
1257,1178,1143,1009cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.8Hz),1.2-1.6(10H,
m),1.7-1.9(2H,m),4.0-4.1(5H,m),6.80(1H,s),
6.98(2H,dd,J=6.9和2.1Hz),7.73(2H,dd,J=6.9
and2.1Hz)
APCI-MASS:m/z=332(M+H+)
制备例185
4-〔3-(4-正己氧基苯基)吡唑-5-基〕苯甲酸甲酯
IR(KBr):2952,1716,1616,1508,1276,1106cm-1
NMR(CDCl3,δ):0.91(3H,t,J=6.3Hz),1.2-1.6(6H,
m),1.7-1.9(2H,m),3.8-4.0(5H,m),6.76(1H,s),
6.86(2H,d,J=8.8Hz),7.54(2H,d,J=8.8Hz),7.77
(2H,d,J=8.4Hz),8.00(2H,d,J=8.4Hz)
APCI-MASS:m/z=379(M+H+)
制备例186
将1-(4-正戊氧基苯基)-3-(4-乙氧羰基苯基)-1-丁烯-3-酮(74.43g)和盐酸羟胺(28.23g)及碳酸钾(56.11g)在乙醇(400ml)中的悬浮液回流4小时。将混合物用乙酸乙酯稀释,用水(×2)洗,用盐水洗,用硫酸镁干燥。减压除去溶剂,得到粗制的肟。向粗制的肟在二氯乙烷(500ml)中的溶液里加入活性二氧化锰(IV)(200g)。将反应混合物回流2小时,过滤。残余物用二氯甲烷洗。减压去除溶剂,残余物用乙腈研制。过滤收集固体,干燥,得到4-〔5-(4-正戊氧基苯基)异噁唑-3-基〕苯甲酸乙酯(21.07g)。
IR(KBr):2945,2872,1717,1615,1508,1280,
1108cm-1
NMR(CDCl3,δ):0.95(3H,t,J=6.9Hz),1.3-1.9(9H,
m),4.01(2H,t,J=6.5Hz),4.41(2H,q,J=7.1Hz),
6.74(1H,s),6.99(2H,d,J=8.8Hz),7.76(2H,d,
J=8.8Hz),7.93(2H,d,J=8.4Hz),8.15(2H,d,
J=8.4Hz)
APCI-MASS:m/z=380(M+H+)
以下化合物(制备例187至190)按照与制备例48相似的方式得到。
制备例187
6-〔4-〔4-(8-甲氧辛氧基)苯基〕哌嗪-1-基〕烟酸甲酯
IR(KBr):2933,2858,1722,1608,1513,1432,1405,
1278,1245cm-1
NMR(CDCl3,δ):1.3-1.9(12H,m),3.16(4H,t,
J=5.0Hz),3.33(3H,s),3.36(2H,t,J=6.5Hz),3.8-
4.0(9H,m),6.64(1H,d,J=9.1Hz),6.85(2H,d,
J=9.2Hz),6.93(2H,d,J=9.2Hz),8.04(1H,dd,
J=9.1和2.2Hz),8.81(1H,d,J=2.2Hz)
APCI-MASS:m/z=456(M+H+)
制备例188
4-〔4-(5-甲氧戊氧基)苯基〕溴苯
IR(KBr):2940,2856,1604,1479,1286,1255,
1124cm-1
NMR(CDCl3,δ):1.5-1.9(6H,m),3.34(3H,s),3.41
(2H,t,J=6.1Hz),3.99(2H,t,J=6.4Hz),6.95(2H,
d,J=8.7Hz),7:4-7.6(6H,m)
APCI-MASS:m/z=349(M+H+)
制备例189
6-(8-甲氧辛氧基)-2-萘甲酸甲酯
NMR(DMSO-d6,δ):1.2-1.6(10H,m),1.7-1.9(2H,m),
3.20(3H,s),3.2 9(2H,t,J=6.4Hz),3.89(3H,s),
4.11(2H,t,J=6.4Hz),7.24(1H,dd,J=9.0和
2.4Hz),7.40(1H,d,J=2.4Hz),7.88(1H,d,
J=8.7Hz),7.94(1H,dd,J=8.7和1.5Hz),8.03(1H,
d,J=9.0Hz),8.55(1H,d,J=1.5Hz)
制备例190
4-〔4-〔4-(8-甲氧辛氧基)苯基〕哌嗪-1-基〕苯甲酸二盐酸盐
IR(KBr):1668.1,1602.6,1511.9,1236.1cm-1
NMR(DMSO-d6,δ):1.2-1.8(12H,m),3.05-3.2(4H,m),
3.29(2H,t,J=7.1Hz),3.33(3H,s),3.4-3.55(4H,
m),3.88(2H,t,J=6.4Hz),6.82(2H,d,J=9.0Hz),
6.94(2H,d,J=9.0Hz),7.02(2H,d,J=8.8Hz),7.79
(2H,d,J=8.8Hz),12.31(1H,s)
以下化合物(制备例191至254)按照与制备例49相似的方式得到。
制备例191
1-〔4-〔4-〔4-〔2-(4-甲基戊基)-2,3-二氢-4H-1,2,4-三唑-3-酮-4-基〕苯基〕哌嗪-1-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1766.5,1693.2,1600.6,1519.6cm-1
制备例192
1-〔4-(4-辛基苯基)-2,3-二氢-4H-1,2,4-三唑-3-酮-2-基-乙酰〕苯并三唑3-氧化物
IR(KBr):2921.6,1753.0,1720.0,1423.2cm-1
NMR(CDCl3,δ):0.88(3H,t,J=6.7Hz),1.2-1.4(10H,
m),1.5-1.8(2H,m),2.65(2H,t,J=7.5Hz),5.46
(2H,s),7.30(2H,d,J=8.5Hz),7.48(2H,d,
J=8.5Hz),7.62(1H,t,J=8.3Hz),7.80(1H,s),7.82
(1H,t,J=8.3Hz),8.05(1H,d,J=8.3Hz),8.37(1H,
d,J=8.3Hz)
制备例193
1-〔4-〔4-〔4-(7-甲氧庚氧基)苯基〕哌嗪-1-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1783.8,1600.6,1511.9,1232.3,1184.1cm-1
NMR(CDCl3,δ):1.3-1.9(10H,m),3.2-3.3(4H,m),
3.34(3H,s),3.38(2H,t,J=6.4Hz),3.5-3.7(4H,
m),3.92(2H,t,J=6.5Hz),6.87(2H,d,J=9.2Hz),
6.95(2H,d,J=9.2Hz),7.00(2H,d,J=9.0Hz),7.3-
7.6(3H,m),8.09(1H,d,J=8.2Hz),8.15(2H,d,
J=9.0Hz)
制备例194
1-〔4-〔4-(4-正庚氧基苯基)哌嗪-1-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1783.8,1600.6,1511.9,1230.4,1184.1cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.3Hz),1.2-1.6(8H,
m),1.7-1.9(2H,m),3.2-3.3(4H,m),3.5-3.7(4H,
m),3.93(2H,t,J=6.5Hz),6.87(2H,d,J=9.2H),
6.95(2H,d,J=9.2Hz),7.00(2H,d,J=9.0Hz),7.3-
7.7(3H,m),8.09(1H,d,J=8.2Hz),8.15(2H,d,
J=9.0Hz)
制备例195
1-〔4-〔4-〔4-(4-甲基戊氧基)苯基〕哌嗪-1-基〕苯甲酰〕苯并三唑3-氧化物
NMR(CDCl3,δ):0.92(6H,d,J=6.6Hz),1.2-1.4(2H,
m),1.5-1.9(3H,m),3.1-3.3(4H,m),3.5-3.7(4H,
m),3.92(2H,t,J=6.6Hz),6.87(2H,d,J=9.3Hz),
6.96(2H,d,J=9.3Hz),7.01(2H,d,J=9.0Hz),7.4-
7.6(3H,m),8.10(1H,d,J=8.2Hz),8.15(2H,d,
J=9.0Hz)
制备例196
1-〔4-〔4-(4-正戊氧基苯基)哌嗪-1-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1787.7,1600.6,1511.9,1232.3,1184.1cm-1
NMR(CDCl3,δ):0.93(3H,t,J=6.9Hz),1.3-1.6(4H,
m),1.7-1.9(2H,m),3.1-3.4(4H,m),3.5-3.8(4H,
m),3.93(2H,t,J=6.6Hz),6.87(2H,d,J=9.2Hz),
6.92(2H,d,J=9.2Hz),7.01(2H,d,J=9.1Hz),7.4-
7.6(3H,m),8.10(1H,d,J=8.2Hz),8.15(2H,d,
J=9.1Hz)
制备例197
1-〔4-〔4-〔8-(1H-四唑-1-基)辛氧基〕苯基〕苯甲酰〕苯并三唑3-氧化物,和
1-〔4-〔4-〔8-(2H-四唑-2-基)辛氧基〕苯基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1778.0,1602.6,1189.9,981.6cm-1
NMR(CDCl3,δ):1.2-1.6(8H,m),1.7-1.9(2H,m),
1.9-2.2(2H,m),4.02(2H,t,J=6.4Hz),4.44和
4.66(2H,t,J=7.1Hz),7.02(2H,d,J=8.8Hz),7.4-
7.6(3H,m),7.63(2H,d,J=8.8Hz),7.79(2H,d,
J=8.6Hz),8.12(1H,d,J=8.2Hz),8.32(2H,d,
J=8.6Hz),8.51和8.60(1H,s)
制备例198
1-〔4-〔4-〔8-(2,6-二甲基吗啉-4-基)辛氧基〕苯基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1778.0,1600.6,977.7cm-1
NMR(CDCl3,δ):1.18(6H,d,J=6.3Hz),1.2-1.7(10H,
m),1.7-2.0(4H,m),2.4-2.6(2H,m),2.9-3.2(2H,
m),3.7-3.9(2H,m),4.01(2H,t,J=6.5Hz),7.02
(2H,d,J=8.8Hz),7.4-7.7(3H,m),7.63(2H,d,
J=8.8Hz),7.79(2H,d,J=8.5Hz),8.12(1H,d,
J=8.1Hz),8.32(2H,d,J=8.5Hz)
制备例199
1-〔6-〔4-(4-辛氧基苯基)哌嗪-1-基〕烟酰〕苯并三唑3-氧化物
IR(KBr压片):2922,2854,1766,1602,1513,1417,
1234,1025,950,813cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.8Hz),1.2-1.5(10H,
m),1.7-1.9(2H,m),3.1-3.3(4H,m),3.9-4.1(6H,
m),6.75(1H,d,J=9.2Hz),6.87(2H,d,J=9.2Hz),
6.95(2H,d,J=9.2Hz),7.4-7.6(3H,m),8.10(1H,
d,J=8.1Hz),8.19(1H,dd,J=9.2和2.4Hz),9.04
(1H,d,J=2.4Hz)
APCI-MASS:m/z=529(M+H+)
制备例200
1-〔2-(4-己氧基苯基)苯并噁唑-5-基-羰基〕苯并三唑3-氧化物
IR(KBr):2950,1774,1623,1504,1265,1176cm-1
NMR(CDCl3,δ):0.93(3H,t,J=6.9Hz),1.3-1.6(6H,
m),1.8-2.0(2H,m),4.07(2H,t,J=6.5Hz),7.06
(2H,d,J=8.9Hz),7.4-7.6(3H,m),7.75(1H,d,
J=8.6Hz),8.13(1H,d,J=8.2Hz),8.2-8.4(3H,m),
8.67(IH,d,J=1.6Hz)
APCI-MASS:m/z=457(M+H+)
制备例201
1-〔4-〔4-(4-正丁氧基苯基)苯基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2958,2871,1776,1600,1398,1255,1211,
1037cm-1
NMR(CDCl3,δ):1.00(3H,t,J=7.2Hz),1.4-1.9(4H,
m),4.03(2H,t,J=6.4Hz),7.01(2H,d,J=8.3Hz),
7.4-7.8(9H,m),7.87(2H,d,J=8.1Hz),8.12(1H,
d,J=8.4Hz),8.36(2H,d,J=7.9Hz)
APCI-MASS:m/z=464(M+H)+
制备例202
1-〔2-(4-庚氧基苯基)吡啶-5-基-羰基〕苯并三唑3-氧化物
IR(KBr):2944,2867,1793,1770,1589,1471,1321,
1093cm-1
NMR(CDCl3,δ):0.91(3H,t,J=6.7Hz ),1.2-1.6(8H,
m),1.7-1.9(2H,m),4.05(2H,t,J=6.5Hz),7.04
(2H,d,J=8.0Hz),7.4-7.6(3H,m),7.91(1H,d,
J=8.5Hz),8.1-8.2(3H,m),8.51(1H,dd,J=8.5和
2.3Hz),9.47(1H,d,J=2.3Hz)
APCI-MASS:m/z=431(M+H+)
制备例203
1-〔2-(2-辛氧基吡啶-5-基)苯并噁唑-5-基-羰基〕苯并三唑3-氧化物
IR(KBr pelet):2925,2854,1787,1623,1479,1263,
989cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.8Hz),1.2-1.5(10H,
m),1.8-1.9(2H,m),4.42(2H,t,J=6.7Hz),6.91
(1H,d,J=8.7Hz),6.4-6.6(3H,m),7.79(1H,d,
J=8.6Hz),8.13(1H,d,J=8.2Hz),8.32(1H,dd,
J=8.6和1.7Hz),8.41(1H,dd,J=8.7和2.4Hz),
8.70(1H,d,J=1.4Hz),9.07(1H,d,J=1.9Hz)
APCI-MASS:m/z=486(M+H+)
制备例204
1-〔2-〔4-(4-己基苯基)苯基〕苯并噁唑-5-基-羰基〕苯并三唑3-氧化物
IR(KBr):2927,2854,1785,1621,1490,1261,1166,
1052cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.2-1.8(8H,
m),2.68(2H,t,J=7.9Hz),7.31(2H,d,J=8.2Hz),
7.4-7.7(5H,m),7.79-7.81(3H,m),8.13(1H,d,
J=8.3Hz),8.3-8.4(3H,m),8.73(1H,d,J=1.3Hz)
APCI-MASS:m/z=517(M+H+)
制备例205
1-〔2-〔4-(4-正丁氧基苯基)苯基〕吡啶-5-基羰基〕苯并三唑3-氧化物
IR(KBr):2956,2933,2871,1774,1650,1591,1471,
1251cm-1
NMR(CDCl3,δ):1.00(3H,t,J=7.2Hz),1.5-1.9(4H,
m),4.03(2H,t,J=6.4Hz),7.02(2H,d,J=8.6Hz),
7.4-7.6(3H,m),7.54(2H,d,J=7.3Hz),7.62(2H,
d,J=8.5Hz),8.02(1H,d,J=8.3Hz),8.13(1H,d,
J=8.2Hz),8.21(2H,d,J=7.9Hz),8.57(1H,dd,
J=8.3和2.0Hz),9.54(1H,d,J=2.0Hz)
APCI-MASS:m/z=465(M+H)+
制备例206b
1-〔4-〔4-(5-苯氧基戊氧基)苯基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2944,2869,1770,1600,1494,1249,
1189cm-1
NMR(CDCl3,δ):1.6-1.8(2H,m),1.8-2.0(4H,m),
4.01(2H,t,J=6.3Hz),4.07(2H,t,J=6.2Hz),6.91
(2H,d,J=8.9Hz),7.04(2H,d,J=8.7Hz),7.3-7.6
(4H,m),7.63(2H,d,J=8.6Hz),7.78(2H,d,
J=8.4Hz),8.12(1H,d,J=8.1Hz),8.32(2H,d,
J=8.4Hz)
APCI-MASS:m/z=494(M+H)+
制备例207
1-〔4-〔5-(4-己氧基苯基)-1,3,4-噁二唑-2-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2956,2921,2856,1778,1612,1496,1261,
1232,1025cm-1
NMR(CDCl3,δ):0.92(3H,t,J=6.7Hz),1.3-1.6(6H,
m),1.8-2.0(2H,m),4.05(2H,t,J=6.5Hz),7.05
(2H,d,J=8.7Hz),7.4-7.6(3H,m),8.10(2H,d,
J=8.7Hz),8.13(1H,d,J=7.4Hz),8.37(2H,d,
J=8.5Hz),8.45(2H,d,J=8.5Hz)
APCI-MASS:m/z=484(M+H)+
制备例208
1-〔4-〔5-(4-正己氧基苯基)-1,3,4-噁二唑-2-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2952,2873,1774,1602,1261,1230,
1176cm-1
NMR(CDCl3,δ):0.93(3H,t,J=6.8Hz),1.3-2.0(8H,
m),4.04(2H,t,J=6.5Hz),7.02(2H,d,J=8.7Hz),
7.4-7.7(3H,m),7.98(2H,d,J=8.7Hz),8.13(1H,
d,J=8.7Hz),8.25(2H,d,J=8.3Hz),8.41(2H,d,
J=8.3Hz)
APCI-MASS:m/z=500(M+H)+
制备例209
1-〔5-(4-辛氧苯基)-1-甲基吡唑-3-基-羰基〕苯并三唑3-氧化物
IR(KBr压片):2939,2852,1776,1687,1612,1448,
1249,995cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.7Hz),1.3-1.5(10H,
m),1.7-1.9(2H,m),4.01(2H,t,J=6.5Hz),4.25
(3H,s),6.97(2H,d,J=6.8Hz),7.4-7.7(4H,m),
7.78(2H,d,J=6.8Hz),8.14(1H,d,J=8.0Hz)
APCI-MASS:m/z=448(M+H+)
制备例210
1-〔4-〔5-(4-正戊氧基苯基)吡唑-3-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):3251,2956,2869,1780,1612,1506,1232,
985cm-1
NMR(CDCl3,δ):0.95(3H,t,J=6.9Hz),1.3-1.6(4H,
m),1.7-2.0(2H,m),4.01(2H,t,J=6.6Hz),6.90
(1H,s),6.99(2H,d,J=8.7Hz),7.4-7.6(5H,m),
8.0-8.2(3H,m),8.33(2H,d,J=8.4Hz)
APCI-MASS:m/z=4 68(M+H+)
制备例211
1-〔5-〔4-(4-正丁氧苯基)苯基〕呋喃-2-基-羰基〕苯并三唑3-氧化物
IR(KBr):2958,2871,1781,1678,1603,1535,1479,
1265cm-1
NMR(CDCl3,δ):1.00(3H,t,J=7.3Hz),1.4-1.9(4H,
m),4.02(2H,t,J=6.4Hz),6.9-7.1(3H,m),7.4-8.2
(11H,m)
APCI-MASS:m/z=351(甲酯)
制备例212
1-(3-(S)-羟基-2-苄基十六烷酰基)苯并三唑3-氧化物
IR(纯相):2854.1,1814.7,1459.8,742.5cm-1
制备例213
1-(3-(R)-苄氧羰基氨基-18-甲氧基十八烷酰基)苯并三唑3-氧化物
IR(KBr):1805.0,1729.8,1695.1cm-1
NMR(DMSO-d6,δ):1.1-1.65(30H,m),3.20(3H,s),
3.28(2H,t,J=6.5Hz),4.01(1H,m),5.06(2H,s),
7.32(5H,m),7.4-7.8(3H,m),8.12(1H,d,J=7Hz)
制备例214
1-(3-(S)-羟基十六烷酰基)苯并三唑3-氧化物
IR(KBr):1710.6,1498.4,1429.0,771.4cm-1
NMR(CDCl3,δ):0.88(3H,t,J=6.4Hz),1.2-1.7(24H,
m),2.00(1H,s),3.1-3.5(2H,m),4.30(1H,m),
7.59(1H,t,J=7.8Hz),7.81(1H,t,J=7.8Hz),8.02
(1H,d,J=8.3Hz),8.421(1H,d,J=8.3Hz)
制备例215
1-(3-甲基-2-十三烯酰基)苯并三唑3-氧化物
IR(KBr):2927.4,1791.5,1633.4,1081.9cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.3Hz),1.1-1.7(20H,
m),2.25(3H,s),6.08(1H,s),7.3-7.6(3H,m),
8.06(1H,d,J=8.2Hz)
制备例216
1-〔4-〔4-〔4-(8-甲氧辛氧基)苯基〕哌嗪-1-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1780.0,1600.6,1511.9,1234.2,1184.1cm-1
NMR(CDCl3,δ):1.3-1.9(12H,m),3.24(4H,t,
J=5.0Hz),3.33(3H,s),3.37(2H,t,J=6.8Hz),3.62
(4H,t,J=5.0Hz),3.92(2H,t,J=6.5Hz),6.8-7.1
(6H,m),7.35-7.65(3H,m),8.09(1H,d,J=8.2Hz),
8.15(2H,d,J=9.0Hz)
制备例217
1-〔3-氟-4-〔4-(4-正己氧基苯基)哌嗪-1-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1778.0cm-1
制备例218
1-〔3-氯-4-〔4-(4-正己氧基苯基)哌嗪-1-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1778.0,1594.8,1511.9,1218.8cm-1
NMR(CDCl3,δ):0.91(3H,t,J=6.5Hz),1.2-1.6(6H,
m),1.6-1.9(2H,m),3.29(4H,t,J=3.6Hz),3.44
(4H,t,J=3.6Hz),3.93(2H,t,J=6.5Hz),6.87(2H,
d,J=9.2Hz),6.97(2H,d,J=9.2Hz),7.19(1H,d,
J=8.6Hz),7.4-7.7(3H,m),8.10(1H,d,J=6.4Hz),
8.14(1H,dd,J=8.6和2.1Hz),8.27(1H,d,
J=2.1Hz)
APCI-MASS:m/z=534(M++H)
制备例219
1-〔4-(4-哌啶子基哌啶-1-基)苯甲酰〕苯并三唑3-氧化物
IR(KBr):1758.8,1602.6,1186.0cm-1
NMR(CDCl3,δ):1.35-1.8(8H,m),1.96(2H,d,
J=13Hz),2.45-2.7(5H,m),2.97(2H,td,J=12.8和
2.6Hz),4.04(2H,d,J=13Hz),6.93(2H,d,
J=9.2Hz),7.35-7.6(3H,m),8.1-8.4(3H,m)
制备例220
1-〔3-〔4-(4-正己氧基苯基)哌嗪-1-基〕哒嗪-6-基羰基〕苯并三唑3-氧化物
IR(KBr):1787.7,1585.2,1511.9,1240.0cm-1
制备例221
1-〔5-〔4-(4-正己氧基苯基)哌嗪-1-基〕吡啶甲酰〕苯并三唑3-氧化物
IR(KBr):1766.5,1575.6,1511.9,1232.3cm-1
NMR(CDCl3,δ):0.91(3H,t,J=6.5Hz),1.2-1.6(6H,
m),1.65-1.9(2H,m),3.27(4H,t,J=5.1Hz),3.66
(4H,t,J=5.1Hz),3.93(2H,t,J=6.5Hz),6.88(2H,
d,J=9.2Hz),6.95(2H,d,J=9.2Hz),7.25(1H,dd,
J=7.6和2.9Hz),7.35-7.6(3H,m),8.09(1H,d,
J=8.2Hz),8.18(1H,d,J=8.9Hz),8.52(1H,d,
J=2.9Hz)
APCI-MASS:m/z=501(M++H)
制备例222
1-〔4-〔4-(4-环己基苯基)哌嗪-1-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1770.3,1602.6,1515.8,1232.3,1186.0cm-1
NMR(CDCl3,δ):1.15-1.5(6H,m),1.65-2.0(4H,m),
2.45(1H,m),3.33(4H,t,J=5.1Hz),3.62(4H,t,
J=5.1Hz),6.92(2H,d,J=8.7Hz),6.99(2H,d,
J=9.2Hz),7.16(2H,d,J=8.7Hz),7.35-7.65(3H,m),
8.09(1H,d,J=8.2Hz),8.15(2H,d,J=9.2Hz)
制备例223
1-〔4-〔4-(4-正己基苯基)哌嗪-1-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1768.4,1602.6,1515.8,1230.4,1184.1cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.5Hz),1.2-1.45(6H,
m),1.5-1.7(2H,m), 2.55(2H,t,J=7.6Hz),3.2-3.4
(4H,m),3.5-3.7(4H,m),6.91(2H,d,J=8.6Hz),
7.00(2H,d,J=9.1Hz),7.13(2H,d,J=8.5Hz),7.35-
7.6(3H,m),8.09(1H,d,J=8.2Hz),8.15(2H,d,
J=9.1Hz)
制备例224
1-〔4-〔4-(4-苯基环己基)哌嗪-1-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1780.0,1762.6,1602.6,1234.2,1182.2cm-1
NMR(CDCl3,δ):1.3-1.7(4H,m),1.95-2.15(4H,m),
2.35-2.6(2H,m),2.79(4H,t,J=5.0Hz),3.49(4H,
t,J=5.0Hz),6.95(2H,d,J=9.0Hz),7.1-7.35(5H,
m),7.35-7.6(3H,m),8.08(1H,d,J=7.1Hz),8.12
(2H,d,J=9.0Hz)
制备例225
1-〔4-〔4-〔1-(4-正己氧基苯基)哌啶-4-基〕哌嗪-1-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1768.4,1602.6,1511.9,1234.2cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.2-1.55(6H,
m),1.6-1.9(4H,m),1.96(2H,d,J=11Hz),2.44
(1H,m),2.64(2H,d,J=1.1Hz),2.77(4H,t,
J=5.0Hz),3.48(4H,t,J=5.0Hz),3.59(2H,d,
J=11Hz),3.91(2H,t,J=6.5Hz),6.7-7.05(6H,m),
7.35-7.6(3H,m),8.08(1H,d,J=6.9Hz),8.12(2H,
d,J=7.7Hz)
制备例226
1-〔4-(4-反-正戊基环己基)苯甲酰〕苯并三唑3-氧化物
IR(KBr):1799.3,1778.0,1608.3,1228.4,977.7cm-1
NMR(CDCl3,δ):0.91(3H,t,J=6.6Hz),1.0-1.7(13H,
m),1.93(4H,d,J=9.8Hz),2.62(1H,t,J=12Hz),
7.35-7.6(5H,m),8.09(1H,d,J=7.9Hz),8.19(2H,
d,J=8.4Hz)
制备例227
1-〔6-(8-甲氧辛氧基)-2-萘甲酰〕苯并三唑3-氧化物
IR(KBr):2931.3,2856.1,1778.0,1623.8cm-1
制备例228
1-(E)-〔3-〔4-〔4-(7-氟代庚氧基)苯基〕苯基〕丙烯酰基〕苯并三唑3-氧化物
IR(KBr):3070.1,2935.1,2859.9,1700.9,1619.9,
1596.8cm-1
NMR(CDCl3,δ):1.30-2.00(10H,m),4.02(2H,t,
J=6.4Hz),4.45(2H,dt,J=47.5和6.2Hz),6.70-
8.65(14H,m)
制备例229
1-(6-庚基萘-2-羰基)苯并三唑3-氧化物
NMR(DMSO-d6,δ):0.75-0.93(3H,m),1.10-1.45(8H,
m),1.55-1.80(2H,m),2.68-2.90(2H,m),7.35-9.06
(10H,m)
APCI-MASS:m/z=388(M++1)
制备例230
1-(E)-〔3-〔4-〔4-(8-甲氧辛氧基)苯基〕苯基〕丙烯酰基〕苯并三唑3-氧化物
制备例231
1-(E)-〔3-〔4-〔4-(5-己烯氧基)苯基〕苯基〕丙烯酰〕苯并三唑3-氧化物
IR(KBr):3072.0,3033.5,2939.0,2865.7,1780.0,
1693.2,1619.9,1596.8cm-1
NMR(DMSO-d6,δ):1.43-1.66(2H,m),1.66-1.90(2H,
m),2.02-2.23(2H,m),3.90-4.16(2H,m),4.90-5.13
(2H,m),5.72-6.00(1H,m),6.93-8.30(14H,m)
APCI-MASS:m/z=337(甲酯,M++1)
制备例232
1-(E)-〔3-〔4-〔4-(4-甲基戊氧基)苯基〕苯基〕丙烯酰〕苯并三唑3-氧化物
IR(KBr):3072.0,3033.5,2952.5,2869.6,1780.0,
1693.2,1618.0,1598.7cm-1
NMR(DMSO-d6,δ):0.90(6H,d,J=6.5Hz),1.20-1.40
(2H,m),1.50-1.90(3H,m),3.90-4.10(2H,m),
6.40-8.30(14H,m)
APCI-MASS:m/z=442(M++1)
制备例233
1-(E)-〔 3-〔4-〔4-(6-氟代己氧基)苯基〕苯基〕丙烯酰〕苯并三唑3-氧化物
IR(KBr):3074.0,3033.5,2939.0,2865.7,1780.0,
1697.1,1598.7cm-1
NMR(DMSO-d6,δ):1.25-1.83(6H,m),4.04(2H,t,
J=6.5Hz),4.45(2H,dt,J=47.5和6.5Hz),6.9-8.3
(14H,m)
APCI-MASS:m/z=460(M++1)
制备例234
1-(E)-〔3-〔4-〔4-(6-甲氧己氧基)苯基〕苯基〕丙烯酰〕苯并三唑3-氧化物
NMR(DMSO-d6,δ):1.30-1.65(6H,m),1.65-1.90(2H,
m),3.22(3H,s),3.22-3.40(2H,m),4.02(2H,t,
J=6.5Hz),6.5-8.3(14H,m)
制备例235
1-〔4-〔3-(4-正己氧基苯基)吡唑-5-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2935,1780,1610,1506 1249,1232,1178,
1087cm-1
NMR(CDCl3,δ):0.91(3H,d,J=6.4Hz),1.2-1.6(6H,
m),1.7-1.9(2H,m),3.98(2H,t,J=6.5Hz),6.8-7.0
(3H,m),7.4-7.6(5H,m),8.00(2H,d,J=8.4Hz),
8.10(1H,d,J=8.1Hz),8.28(1H,d,J=8.4Hz)
APCI-MASS:m/z=482(M+H+)
制备例236
1-〔4-〔4-〔4-(6-甲氧己氧基)苯基〕苯基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2935,2858,1774,1600,1490,1257,
1211cm-1
NMR(CDCl3,δ):1.4-1.9(8H,m),3.35(3H,s),3.40
(2H,t,J=6.3Hz),4.02(21H,t,J=6.4Hz),7.00(2H,
d,J=8.7Hz),7.4-7.8(7H,m),7.87(2H,d,
J=8.4Hz),8.12(1H,d,J=8.2Hz),8.36(2H,d,
J=8.4Hz)
APCI-MASS:m/z=522(M+H+)
制备例237
1-〔4-〔5-〔4-(8-甲氧辛氧基)苯基〕-1,3,4-噻二唑-2-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2929,2854,1776,1602,1459,1255cm-1
NMR(CDCl3,δ):1.2-1.6(10H,m),1.7-1.9(2H,m),
3.33(3H,s),3.37(2H,d,J=6.4Hz),4.03(2H,d,
J=6.5Hz),7.00(2H,d,J=8.9Hz),7.4-7.6(3H,m),
7.97(2H,d,J=8.9Hz),8.12(1H,d,J=8.2Hz),8.23
(2H,d,J=8.7Hz),8.39(2H,d,J=8.7Hz)
APCI-MASS:m/z=558(M+H+)
制备例238
1-〔4-(4-正丁氧苯基)肉桂酰〕苯并三唑3-氧化物
IR(KBr):2952,2867,1778,1598,1496,1249,
1186cm-1
NMR(CDCl3,δ):0.99(3H,t,J=7.3Hz),1.55(2H,tq,
J=7.0和7.3Hz),1.78(2H,tt,J=7.0和6.4Hz),
4.02(2H,t,J=6.4Hz),6.75(1H,d,J=16.0Hz),7.00
(2H,d,J=8.7Hz),7.4-8.2(9H,m)
APCI-MASS:m/z=414(M+H+)
制备例239
1-〔4-〔5-(4-环己基苯基)-1,3,4-噻二唑-2-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2925,2850,1778,1230,989cm-1
NMR(CDCl3,δ):1.2-1.6(5H,m),1.7-2.0(5H,m),
2.5-2.7(1H,m),7.37(2H,d,J=8.3Hz),7.4-7.6
(3H,m),7.97(2H,d,J=8.3Hz),8.13(1H,d,
J=8.2Hz),8.26(2H,d,J=8.6Hz),8.42(2H,d,
J=8.6Hz)
APCI-MASS:m/z=482 (M+H)+
制备例240
1-〔4-〔 5-〔4-(4-正丙氧基苯基)苯基〕-1,3,4-噁二唑-2-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1778,1604,1488,1249,1232,998cm-1
NMR(CDCl3,δ):1.07(3H,t,J=7.4Hz),1.85(2H,tq ,
J=6.5和7.4Hz),7.02(2H,d,J=8.8Hz),7.4-7.7
(3H,m),7.61(2H,d,J=8.8Hz),7.75(2H,d,
J=8.5Hz),8.14(1H,d,J=8.2Hz),8.22(2H,d,
J=8.5Hz),8.40(2H,d,J=8.8Hz),8.48(2H,d,
J=8.8Hz)
APCI-MASS:m/z=518(M+H)+
制备例241
1-〔4-(5-正壬基-1,3,4-噁二唑-2-基〕苯甲酰苯并三唑3-氧化物
IR(KBr):2919,2850,1780,1565,1415,1251cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.7Hz),1.2-1.6(12H,
m),1.8-2.0(2H,m),2.98(2H,t,J=7.7Hz),7.4-7.6
(3H,m),8.12(1H,d,J=9.0Hz),8.28(2H,d,
J=8.7Hz),8.42(2H,d,J=8.7Hz)
APCI-MASS:m/z=434(M+H+)
制备例242
1-〔4-〔3-(4-正己氧基苯基)-1,2,4-噁二唑-5-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2946,2869,1780,1251,1230,1001cm-1
NMR(CDCl3,δ):0.92(3H,t,J=6.8Hz),1.3-1.6(6H,
m),1.8-1.9(2H,m),4.04(2H,t,J=6.5Hz),7.03
(2H,d,J=8.9Hz),7.4-7.6(3H,m),8.0-8.2(3H,m),
8.46(4H,s)
APCI-MASS:m/z=484(M+H+)
制备例243
1-〔4-〔5-(4-正辛氧基苯基)-1,3,4-噻二唑-2-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2925,2856,1774,1602,1259,1232,989cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.7Hz),1.1-1.6(10H,
m),1.7-1.9(2H,m),4.04(2H,t,J=6.5Hz),7.01
(2H,d,J=8.9Hz),7.4-7.6(3H,m),7.97(2H,d,
J=8.8Hz),8.12(1H,d,J=8.2Hz),8.24(2H,d,
J=8.6Hz),8.40(2H,d,J=8.6Hz)
APCI-MASS:m/z=528(M+H+)
制备例244
1-〔4-〔5-(4-反-正戊基环己基)-1,3,4-噻二唑-2-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2952,2919,2848,1785,1444,1226,991cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.9Hz),1.0-1.7(13H,
m),1.94(2H,d,J=12.0Hz),2.27(2H,d,J=12.0Hz),
3.19(1H,tt,J=12.0和3.6Hz),7.4-7.6(3H,m ),
8.12(1H,d,J=8.0Hz),8.19(2H,d,J=8.6Hz),8.38
(2H,d,J=8.6Hz)
APCI-MASS:m/z=476(M+H+)
制备例245
1-〔4-〔3-(4-正戊氧基苯基)异噁唑-5-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2948,2867,177 6,1610,1436,1253,1002cm-1
NMR(CDCl3,δ):0.95(3H,t,J=7.1Hz),1.2-1.6(4H,
m),1.7-1.9(2H,m),4.02(2H,t,J=6.5Hz),7.0-7.1
(3H,m),7.4-7.6(3H,m),7.81(2H,d,J=8.8Hz),
8.06(2H,d,J=8.6Hz),8.12(1H,d,J=8.0Hz),8.39
(2H,d,J=8.6Hz)
APCI-MASS:m/z=469 (M+H+)
制备例246
1-〔4-〔5-〔4-(8-甲氧辛氧基)苯基〕-1,3,4-噁二唑-2-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2923,2854,1787,1608,1494,1255,1228,
993cm-1
NMR(CDCl3,δ):1.2-1.6(10H,m),1.7-1.9(2H,m),
3.34(3H,s),3.38(2H,t,J=6.4Hz),4.05(2H,t,
J=6.5Hz),7.04(2H,d,J=8.8Hz),7.4-7.6(3H,s),
8.1-8.2(3H,s),8.36(2H,d,J=8.7Hz),8.45(2H,
d,J=8.7Hz)
APCI-MASS:m/z=542(M+H+)
制备例247
1-〔4-〔4-(6-苯基哒嗪-3-基-氧〕苯基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1783,1604,1423,1284,985cm-1
NMR(CDCl3,δ):7.2-8.2(15H,m),8.12(2H,d,
J=8.3Hz),8.3 6(2H,d,J=8.4Hz)
APCI-MASS:m/z=486(M++1)
制备例248
1-〔4-〔5-(4-正辛氧基苯基)-1,3,4-噁二唑-2-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2925,2854,1780,1610,1496,1257,1228.
1180cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.8Hz),1.2-2.0(12H,
m),4.05(2H,t,J=6.5Hz),7.05(2H,d,J=8.7Hz),
7.4-7.6(3H,m),8.0-8.2(3H,m),8.37(2H,d,
J=8.6Hz),8.45 (2H,d,J=8.6Hz)
APCI-MASS:m/z=512(M+H+)
制备例249
1-〔4-〔2-(4-正己氧基苯基)嘧啶-6-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2948,2861,1780,1552,1413,1378,987cm-1
NMR(CDCl3,δ):0.92(3H,t,J=6.8Hz),1.2-1.6(6H,
m),1.8-2.0(2H,m),4.06(2H,t,J=6.5Hz),7.04
(2H,d,J=9.0Hz),7.4-7.6(3H,m),7.64(1H,d,
J=5.2Hz),8.13(1H,d,J=8.2Hz),8.44(4H,s),8.55
(2H,d,J=9.0Hz),8.90(1H,d,J=5.2Hz)
APCI-MASS:m/z=494(M+H+)
制备例250
1-〔4-〔4-〔8-(2-乙氧乙氧基)辛氧基〕苯基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2933,2861,1778,1598,1247,1186,977cm-1
NMR(CDCl3,δ):1.22(3H,t,J=7.0Hz),1.3-2.0(14H,
m),3.4-3.6(6H,m),4.02(2H,t,J=6.5Hz),7.02
(2H,d,J=8.8Hz),7.4-7.6(3H,m),7.62(2H,d,
J=8.8Hz),7.78(2H,d,J=8.6Hz),8.10(1H,d,
J=8.9Hz),8.31(2H,d,J=8.6Hz)
APCI-MASS:m/z=532(M+H+)
制备例251
1-〔4-〔4-〔7-(哌啶-1-基-羰基)庚氧基〕苯基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2935,2856,1774,1631,1598,1255,
1191cm-1
NMR(CDCl3,δ):1.3-2.0(16H,m),2.37(2H,t,
J=7.6Hz),3.48(4H,s),4.02(2H,t,J=6.4Hz),7.02
(2H,d,J=8.6Hz),7.4-7.6(3H,m),7.63(2H,d,
J=8.6Hz),7.78(2H,d,J=8.3Hz),8.11(1H,d,
J=8.1Hz),8.31(2H,d,J=8.3Hz)
APCI-MASS:m/z=541(M+H+)
制备例252
1-〔6-〔4-(4-正庚氧基苯基)哌嗪-1-基〕烟酰〕苯并三唑3-氧化物
IR(KBr):2929,2856,1762,1604,1510,1240cm立
NMR(CDCl3,δ):0.89(3H,t,J=6.7Hz),1.2-1.9(10H,
m),3.20(4H,t,J=5.0Hz),3.8-4.0(6H,m),6.75
(1H,d,J=9.5Hz),6.86(2H,d,J=9.3Hz),6.95(2H,
d,J=9.3Hz),7.3-7.6(3H,m),8.10(1H,d,
J=8.2Hz),8.19(1H,dd,J=9.2和2.3Hz),9.05(1H,
d,J=2.3Hz)
APCI-MASS:m/z=515·(M+H+)
制备例253
1-〔6-〔4-〔4-(8-甲氧辛氧基)苯基〕哌嗪-1-基〕烟酰〕苯并三唑3-氧化物
IR(KBr):2929,2854,1766,1602,1510,1419,
1234cm-1
NMR(CDCl3,δ):1.3-1.9(12H,m),3.2-3.3(4H,m),
3.33(3H,s),3.36(2H,t,J=6.4Hz),3.92(2H,t,
J=6.5Hz),4.0-4.2(4H,m),6.75(1H,,d,J=9.1Hz),
6.87(2H,d,J=8.9Hz),7.0-7.2(2H,m),7.4-7.6
(3H,m),8.09(1H,d,J=8.1Hz),8.20(1H,dd,J=9.1
and2.3Hz),9.05(1H,d,J=2.3Hz)
APCI-MASS:m/z=559(M+H+)
制备例254
1-〔4-〔5-〔4-(4-正丙氧基苯基)苯基〕-1,3,4-噻二唑-2-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):1774,1600,1234,985cm-1
NMR(CDCl3,δ):1.07(3H,t,J=7.3Hz),1.85(2H,tq,
J=6.5和7.3Hz),3.99(2H,t,J=6.5Hz),7.01(2H,
d,J=8.7Hz),7.4-7.7(5H,m),7.72(2H,d,
J=8.7Hz),8.1-8.2(2H,m),8.28(2H,d,J=8.6Hz),
8.44(2H,d,J=8.6Hz)
APCI-MASS:m/z==534(M+H)+
以下化合物(制备例255至256)按照与制备例32相似的方式得到。
制备例255
6-庚基萘-2-羧酸
NMR(CDCl3,δ): 0.88(3H,t,J=6.6Hz),1.15-1.53(8H,
m),1.58-1.88(2H,m),2.80(2H,t,J=7.6Hz),7.42
(1H,dd,J=1.7and8.4Hz),7.67(1H,s),7.84(1H,
d,J=8.6Hz),7.90(1H,d,J=8.4Hz),8.09(1H,dd,
J=1.7and8.6Hz),8.68(1H,s)
APCI-MASS:m/z=271(M++1),285(甲酯+-1)
制备例256
3-(E)-〔4-〔4-(7-氟代庚氧基)苯基〕苯基〕丙烯酸
IR(KBr):3037.3,2935.1,2861.8,1679.7,1633.4,
1600.6cm-1
NMR(DMSO-d6,δ):1.30-1.85(10H,m),4.01(2H,t,
J=6.4Hz),4.44(2H,dt,J=47.6和6.1Hz),6.54
(1H,d,J=15.9Hz),7.02(2H,d,J=8.7Hz),7.53-7.80
(7H,m)
制备例257
在环境温度下向4-甲基戊醇(3.0ml)在吡啶(20ml)中的溶液里依次加入对甲苯磺酰氯(4.6g)和4-N,N-二甲基氨基吡啶(1.5g)。在环境温度下搅拌之后,将反应混合物加入到乙酸乙酯(100ml)和水(100ml)的混合物中。分离出的有机层依次用盐酸(1N)、水、碳酸氢钠水溶液和盐水洗,用硫酸镁干燥。蒸发后得到1-对甲苯磺酰氧基-4-甲基戊烷(5.30g)
NMR(CDCl3,δ):0.83(6H,d,J=6.6Hz),1.48(1H,
sept,J=6.6Hz),1.50-1.70(2H,m),2.45(3H,s),
4.00(2H,t,J=6.6Hz),7.34(2H,d,J=8.1Hz),7.79
(2H,d,J=8.1Hz)
APCI-MASS:m/z=257(M++1)
制备例258
在-60℃于10分钟内向4-溴-4’-正丁氧基联苯(3.05g)在四氢呋喃(60ml)中的溶液里加入正丁基锂在正己烷(7.74ml)中的1.55M溶液。将溶液在-30℃搅拌1.5小时,冷却到-60℃。在5分钟内向溶液中加入硼酸三异丙酯(3.46ml),混合物不加冷却地搅拌1.5小时。向此溶液中加入1N盐酸(20ml),将溶液搅拌30分钟,用乙酸乙酯萃取。分离出有机层,用水和盐水洗,用硫酸镁干燥。减压除去溶剂,残余物用正己烷研制。过滤收集固体,减压干燥,得到4-(4-正丁氧基苯基)苯基硼酸(2.31g)。
IR(KBr):3398,2956,2919,2871,1604,1531,1392,
1257cm-1
NMR(DMSO-d6,δ):0.94(3H,t,J=7.3Hz),1.4-1.8(4H,
m),4.01(2H,t,J=6.3Hz),7.01(2H,d,J=8.7Nz),
7.58(2H,d,J=7.9Hz),7.62(2H,d,J=8.7Hz),7.84
(2H,d,J=7.9Hz),8.03(2H,s)
以下化合物(制备例259至260)按照与制备例258相似的方法得到。
制备例259
4-〔4-(6-甲氧己氧基)苯基〕苯基硼酸
IR(KBr):3448,3392,2937,2861,1606,1529,1346,
1288cm-1
NMR(DMSO-d6,δ):1.3-1.8(8H,m),3.21(3H,s),3.31
(2H,t,J=6.3Hz),3.99(2H,t,J=6.4Hz),7.00(2H,
d,J=8.7Hz),7.5-7.7(4H,m),7.84(2H,d,
J=8.1Hz),8.03(2H,s)
APCI-MASS:m/z=329(M+H+)
制备例260
4-〔4-(5-甲氧戊氧基)苯基〕苯基硼酸
IR(KBr):3473,3369,3330,2935,2863,1604,1531,
1338,1251cm-1
NMR(DMSO-d6,δ):1.4-1.8(6H,m),3.22(3H,s),3.3-
3.4(2H,m),3.99(2H,,t,J=6.4Hz),7.00(2H,d,
J=8.7Hz),7.58(2H,d,J=8.0Hz),7.61(2H,d,
J=8.7Hz),7.84(2H,d,J=8.0Hz),8.04(2H,s)
APCI-MASS:m/z=315(M+H+)
制备例261
向4-甲氧羰基苯基硼酸(648mg)和4-碘代-1-庚基吡唑(876mg)和Pd(pph3)4(173mg)在1,2-二甲氧基乙烷(10ml)中的悬浮液里加入2M Na2CO3水溶液(3.6ml)。将反应混合物在80℃于N2气搅拌2小时,倒入冰水中,用乙酸乙酯萃取。有机层用盐水洗,用MgSO4干燥。减压去除溶剂。残余物在硅胶60(Merk)上进行柱色谱,用正己烷/乙酸乙酯(80∶20)洗脱。将含有目标化合物的级分合并,减压蒸发,得到1-庚基-4-(4-甲氧羰基苯基)吡唑(0.20g)。
IR(KBr压片):2952,2920,2848,1712,1610,1288,
1114,769cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.7Hz),1.1-1.4(8H,
m),1.7-1.9(2H,m),3.85(3H,s),4.11(2H,t,
J=7.0Hz),7.72(2H,d,J=8.5Hz),7.93(2H,d,
J=8.5Hz),7.99(1H,s),8.34(1H,s)
APCI-MASS:m/z=301(M+H+)
以下化合物(制备例262至268)按照与制备例261相似的方式得到。
制备例262
4-〔4-(4-正丁氧基苯基)苯基〕苯甲酸乙酯
IR(KBr):2958,2935,2871,1714,1602,1396,1280,
1108cm-1
NMR(CDCl3,δ):0.99(3H,t,J=7.3Hz),1.4-2.0(7H,
m),4.02(2H,t,J=6.4Hz),4.40(2H,q,J=7.1Hz),
6.98(2H,d,J=6.8Hz),7.56(2H,d,J=6.8Hz),7.66
(4H,s),7.68(2H,d,J=8.4Hz),8.12(2H,d,
J=8.4Hz)
APCI-MASS:m/z=375(M+H)+
制备例263
6-(4-庚氧基苯基)烟酸甲酯
IR(KBr):2954,2859,1724,1597,1288,1251,1116,
783cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.6Hz),1.2-1.5(8H,
m),1.7-1.9(2H,m),3.96(3H,s),4.03(2H,t,
J=6.5Hz),7.00(2H,d,J=8.8Hz),7.75(1H,d,
J=8.4Hz),8.02(1H,d,J=8.8Hz),8.30(1H,dd,
J=8.4和2.2Hz),9.23(1H,d,J=2.2Hz)
APCI-MASS:m/z=328(M+H+)
制备例264
6-〔4-(4-正丁氧基苯基)苯基〕烟酸甲酯
IR(KBr):2956,2933,2871,1724,1598,1282,
1118cm-1
NMR(CDCl3,δ):1.00(3H,t,J=7.3Hz),1.4-1.9(4H,
m),3.98(3H,s),4.02(2H,t,J=6.4Hz),7.00(2H ,
d,J=8.8Hz),7.59(2H,d,J=8.8Hz),7.70(2H,d,
J=8.5Hz),7.86(1H,d,J=8.8Hz),8.13(2H,d,
J=8.5Hz),8.37(1H,dd,J=8.8和1.6Hz),9.30(1H,
d,J=1.6Hz)
APCI-MASS:m/z=362(M+H+)
制备例265
5-〔4-(4-正丁氧基苯基)苯基〕呋喃2-羧酸甲酯
IR(KBr):2958,2933,2873,1716,1483,1303,
1139cm-1
NMR(CDCl3,δ):0.99(3H,t,J=7.3Hz),1.5-1.9(4H,
m),3.93(3H,s),4.01(2H,t,J=6.4Hz),6.75(1H,
d,J=3.6Hz),6.98(2H,d,J=8.7Hz),7.26(1H,d,
J=3.6Hz),7.56(2H,d,J=8.4Hz),7.61(2H,d,
J=8.7Hz),7.83(2H,d,J=8.4Hz)
APCI-MASS:m/z=351(M+H)+
制备例266
4-〔4-〔4-(6-甲氧己氧基)苯基〕苯基〕苯甲酸乙酯
IR(KBr):2937,2863,1712,1602,1396,1278,
1108cm-1
NMR(CDCl3,δ):1.4-2.0(11H,m),3.34(3H,s),3.39
(2H,t,J=6.4Hz),4.01(2H,t,J=6.4Hz),4.41(2H,
q,J=7.1Hz),6.98(2H,d,J=8.7Hz),7.56(2H,d,
J=8.7Hz),7.6-7.8(6H,m),8.12(2H,d,J=8.4Hz)
APCI-MASS:m/z=433(M+H+)
制备例267
4-〔4-〔4-(5-甲氧戊氧基)苯基〕苯基〕苯甲酸
IR(KBr):2939,2859,1679,1587,1396,1321,1292,
1126cm-1
NMR(DMSO-d6,δ):1.3-1.8(6H,m),3.21(3H,s),3.2-
3.4(2H,m),4.01(2H,t,J=6.5Hz),7.04(2H,d,
J=8.6Hz),7.66(2H,d,J=8.6Hz),7.7-7.9(6H,m),
8.03(2H,d,J=8.2Hz)
APCI-MASS:m/z=391(M+H+)
制备例268
4-〔4-〔4-(5-甲氧戊氧基)苯基〕苯基〕苯基乙酸甲酯
IR(KBr):2937,2863,1739,1604,1492,1255cm-1
NMR(CDCl3,δ):1.5-2.0(6H,m),3.34(3H,s),3.42
(2H,t,J=6.3Hz),3.68(2H,s),3.72(3H,s),4.02
(2H,t,J=6.4Hz),6.97(2H,d,J=8.7Hz),7.36(2H,
d,J=8.2Hz),7.5-7.7(8H,m)
APCI-MASS:m/z=419(M+H+)
制备例269
将3-〔2-(4-己基苯氨基)乙基〕-2-氧代噁唑烷盐酸盐(2.131g)在25%的氢溴酸/乙酸溶液(13.04ml)中的溶液于环境温度下搅拌96小时。将反应混合物与二异丙醚一起研磨。过滤收集沉淀,加到15ml乙醇中。将溶液回流5小时,与二异丙醚一起研磨。过滤收集沉淀,得到1-(4-正己基苯基)哌嗪二氢溴酸盐(2.413g)。
IR(KBr):2921.6,2711.4,2485.8,1452.1,1012.4cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.6Hz),1.1-1.4(6H,
m),1.4-1.6(2H,m),2.49(2H,t,J=8.4Hz),3.1-3.4
(8H,m),6.54(2H,s),6.90(2H,d,J=8.7Hz),7.08
(2H,d,J=8.7Hz),8.78(1H,s)
APCI-MASS:m/z=247(M++H)
以下化合物(制备例270至274)按照与制备例269相似的方式得到。
制备例270
4-〔4-(4-正己基苯基)哌嗪-1-基〕苯甲酸二氢溴酸盐
IR(KBr):2956.3,1691.3,1664.3,1602.6,1232.3cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.5Hz),1.2-1.4
(10H,m),1.4-1.6(2H,m),2.51(2H,t,J=7.4Hz),
3.2-3.6(8H,m),7.0-7.2(6H,m),7.81(2H,d,
J=8.8Hz)
APCI-MASS:m/z=367(M++H)
制备例271
1-(4-环己基苯基)哌嗪二氢溴酸盐
IR(KBr):2927.4,1510.0,1452.1cm-1
NMR(DMSO-d6,δ):1.1-1.5(6H,m),1.6-1.9(4H,m),
2.41(1H,m),3.1-3.4(8H,m),6.91(2H,d,
J=8.7Hz),7.11(2H,d,J=8.7Hz),8.78(1H,s)
APCI-MASS:m/z=245(M++H)
制备例272
4-〔4-(4-环己基苯基)哌嗪-1-基〕苯甲酸二氢溴酸盐
IR(KBr):1668.1,1602.6,1230.4,1189.9cm-1
APCI-MASS:m/z=365(M++H)
制备例273
3-氟-4-〔4-(4-羟苯基)哌嗪-1-基〕苯甲酸二氢溴酸盐
IR(KBr):1708.6,1610.3cm-1
NMR(DMSO-d6,δ):3.2-3.6(8H,m),6.81(2H,d,
J=8.6Hz),7.0-7.4(3H,m),7.4-7.8(2H,m)
APCI-MASS:m/z=317(M++H)
制备例274
4-〔4-(4-羟苯基)哌嗪-1-基〕苯甲酸二氢溴酸盐
IR(KBr):1670.1,1604.5,1226.5,775.2cm-1
NMR(DMSO-d6,δ):3.0-3.2(4H,m),3.3-3.5(4H,m),
6.68(2H,d,J=8.8Hz),6.85(2H,d,J=8.8Hz),7.02
(2H,d,J=8.8Hz),7.79(2H,d,J=8.8Hz),8.86(1H,
s),12.29(1H,s)
APCI-MASS:m/z=299(M+H+)
制备例275
将4-正己氧基苯胺(10g)、丙烯酸乙酯(56.1ml)、冰乙酸(19.25ml)和氯化亚铜(1.02g)的混合物在氮气下加热搅拌回流26小时。将该冷产物在乙醚中的溶液与水一起摇荡,然后与氨水摇荡。取出有机层,用硫酸镁干燥。滤除硫酸镁,滤液减压蒸发。残余物在硅胶柱色谱,用己烷-乙酸乙酯(9∶1)洗脱。将含有目标化合物的级分合并,减压蒸发,得到3-〔N-(2-乙氧羰基乙基)-N-(4-己氧基苯基)氨基〕丙酸乙酯(15.756g)。
IR(纯相):1733.7,1513.8,1241.9,1182.2cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.2-1.55(6H,
m),1.24(6H,t,J=7.1Hz),1.65-1.85(2H,m),2.51
(4H,t,J=7.2Hz),3.53(4H,t,J=7.2Hz),3.89(2H,
t,J=6.5Hz),4.12(4H,q,J=7.1Hz),6.72(2H,d,
J=9.3Hz),6.83(2H,d,J=9.3Hz)
APCI-MASS:m/z=394(M++H)
制备例276
将4-甲酰苯甲酸甲酯(4.92g)、盐酸羟胺(5.21g)和乙酸钠(6.15g)在乙醇(50ml)中的悬浮液回流2小时。将混合物倒入水中,用乙酸乙酯萃取,分离出的有机层用盐水洗,用硫酸镁干燥。减压去除溶剂,得到4-甲氧羰基苯甲醛肟(5.28g)。
IR(KBr):3291,1727,1438,1284,1112cm-1
NMR(CDCl3,δ):3.93(3H,s),7.65(2H,d,J=8.3Hz),
8.10(2H,d,J=8.3Hz),8.18(1H,s),8.27(1H,s)
APCI-MASS:m/z=180
以下化合物按照与实施例276相似的方式得到。
制备例277
N-羟基-4-正己氧基苯甲脒
IR(KBr):3446,3349,2937,2865,1650,1610,1519,
1392,1253cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.4Hz),1.2-1.8(8H,
m),3.97(2H,t,J=6.5Hz),5.70(2H,s),6.90(2H,
d,J=8.4Hz),7.58(2H,d,J=8.4Hz),9.43(1H,s)
APCI-MASS:m/z=237(M+H)+
制备例278
向4-甲氧羰基苯甲醛肟(896mg)在N,N-二甲基甲酰胺(10ml)中的溶液里加入在1,4-二噁烷(1.38ml)中的4N盐酸和过硫酸氢钾制剂(Oxone R)(1.69g)。将悬浮液在环境温度下搅拌16小时,倒入冰水中。用乙酸乙酯萃取目标化合物,有机层用盐水洗,用硫酸镁干燥。减压去除溶剂,得到4-甲氧羰基苯甲醛肟氯化物(1.05g)。
IR(KBr):3390,1710,1436,1405,1284,1232,1116,
1016cm-1
NMR(CDCl3,δ):3.95(3H,s),8.93(2H,d,J=8.3Hz),
8.10(2H,d,J=8.7Hz),8.39(1H,s)
APCI-MASS:m/z=176(M-H+-HCl)
制备例279
将4-氧代-1-(4-正己氧基苯基)哌啶-3-羧酸乙酯(1.437g)在20%盐酸(7.2ml)中的溶液回流2小时,冷却,用60%氢氧化钠水溶液碱化,用乙酸乙酯萃取。分出有机层,用硫酸镁干燥。滤除硫酸镁,将滤液减压蒸发,得到1-(4-正己氧基苯基)-4-哌啶酮(0.959g)。
IR(纯相):2931.3,1716.3,1511.9,1243.9,825.4cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.2-1.6(6H,
m),1.65-1.85(2H,m),2.57(4H,t,J=6.1Hz),3.46
(4H,t,J=6.1Hz),3.92(2H,t,J=6.5Hz),6.85(2H,
d,J=9.3Hz),6.95(2H,d,J=9.3Hz)
APCI-MASS:m/z=276(M++H)
制备例280
将4-〔4-(7-溴代庚氧基)苯基〕溴苯(0.25g)在氟化四正丁铵(四氢呋喃溶液,1M,2.9ml)中的溶液加热至50℃并保持2小时,在冷却到环境温度之后,将溶液加到乙酸乙酯(20ml)和水(20ml)的混合物中。分离出的有机层依次用水和盐水洗,用硫酸镁干燥。蒸发后得到残余物,将其在硅胶(30ml)上层析,用正己烷和乙酸乙酯的混合物(100∶0-97∶3,v/v)洗脱。收集含目标化合物的级分并蒸发之,残余物与正己烷一起研制,得到4-〔4-(7-氟代庚氧基)苯基〕溴苯(104mg)
IR(KBr):2937.1,2859.9,1606.4cm-1
NMR(CDCl3,δ):1.20-1.90(10H,m),3.99(2H,t,
J=6.4Hz),4.45(2H,dt,J=47.3和6.1Hz),6.95
(2H,d,J=6.7Hz),7.40(2H,d,J=6.7Hz),7.47(2H,
d,J=6.7Hz),7.52(2H,d,J=6.7Hz)
以下化合物按照与制备例280相似的方式得到。
制备例281
4-〔4-(6-氟代己氧基)苯基〕溴苯
NMR(CDCl3,δ):1.40-1.95(8H,m),4.01(2H,t,
J=6.4Hz),4.47(2H,dt,J=47.5和6.0Hz),6.95
(2H,d,J=8.6Hz),7.35-7.59(6H,m)
制备例282
将4-〔4-(8-溴代辛氧基)苯基〕溴苯(3.7g)在甲醇钠(4.9M甲醇溶液,17ml)、N,N-二甲基甲酰胺(20ml)和四氢呋喃(8ml)的混合物中的溶液于80℃加热3小时。将反应混合物加到乙酸乙酯(200ml)和水(100ml)的混合物中。分离出的有机层依次用水和盐水洗,用硫酸镁干燥。蒸发后得到残余物,将其进行柱色谱(硅胶,100ml),用正己烷洗脱,得到4-〔4-(8-甲氧辛氧基)苯基〕溴苯(2.73g)。
IR(KBr):2935.1,2858.0,1604.5cm-1
NMR(CDCl3,δ):1.25-1.70(10H,m),1.70-1.95(2H,
m),3.33(3H,s),3.37(2H,t,J=6.5Hz),3.99(2H,
t,J=6.5Hz),6.95(2H,d,J=8.8Hz),7.35-7.66(6H,
m)
APCI-MASS:m/z=391(M+)
以下化合物(制备例283至284)按照与制备例282相似的方式得到。
制备例283
4-〔4-(6-甲氧己氧基)苯基〕溴苯
NMR(CDCl3,δ):1.50-1.70(6H,m),1.70-1.95(2H,m),
3.34(3H,s),3.40(2H,t,J=6.2Hz),3.99(2H,t,
J=6.5Hz),6.95(2H,d,J=8.7Hz),7.30-7.60(6H,m)
APCI-MASS:m/z=365(M++2)
制备例284
4-〔4-(7-甲氧庚氧基)苯基〕溴苯
IR(KBr):2935.1,2854.1,1604.5cm-1
NMR(CDCl3,δ):1.25-1.70(8H,m),1.70.1.95(2H,m),
3.33(3H,s),3.37(2H,t,J=6.4Hz),3.98(2H,t,
J=6.5Hz),6.95(2H,d,J=8.8Hz),7.35-7.56(6H,m)
APCI-MASS:m/z=379(M++2)
制备例285
将N-(4-辛基苯基)-N’-氨基脲、乙酸甲脒(12.76g)和N-肼基甲酰-4-辛基苯胺(0.458g)在N,N-二甲基甲酰胺(19.4ml)中于150℃搅拌6小时。将反应混合物与水一起研磨。过滤收集沉淀物,用水洗,得到4-(4-辛基苯基)-2,3-二氢-4H-1,2,4-三唑-3-酮(4.27g)。
IR(KBr):3214.8,3085.5,1704.8cm-1
NMR(CDCl3,δ):0.88(3H,t,J=6.7Hz),1.2-1.5(10H,
m),1.5-1.8(2H,m),2.64(2H,t,J=7.9Hz),7.29
(2H,d,J=8.5Hz),7.43(2H,d,J=8.5Hz),7.67(1H,
d,J=1.3Hz),10.31(1H,s)
APCI-MASS:m/z=274(M+H+)
以下化合物(制备例286)按照与制备例285相似的方式得到。
制备例286
4-〔4-(4-叔丁氧羰基哌嗪-1-基)苯基〕-2,3-二氢-4H-1,2,4-三唑-3-酮
IR(KBr):3200,1699.0,918.0cm-1
NMR(CDCl3,δ):1.49(9H,s),3.17(4H,t,J=4.9Hz),
3.60(4H,t,J=4.9Hz),7.00(2H,d,J=9.0Hz),7.40
(2H,d,J=9.0Hz),7.63(1H,s),10.4(1H,s)
APCI-MASS:m/z=346(M+H+)
制备例287
将6-(1-庚炔基)萘-2-羧酸甲酯(4.51g)和氧化铂(0.4g)在四氢呋喃中的混合物在3.5大气压的氢气下搅拌5小时。滤除催化剂,将滤液蒸发,得到6-庚基萘-2-羧酸甲酯(4.40g)
NMR(CDCl3,δ):0.88(3H,t,J=6.6Hz),1.16-1.50(8H,
m),1.50-1.80(2H,m),2.78(2H,t,J=7.6Hz),3.97
(3H,s),7.39(1H,dd,J=17和8.4Hz),7.64(1H,
s),7.79(1H,d,J=8.6Hz),7.86(1H,d,J=8.4Hz),
8.02(1H,dd,J=1.7和8.6Hz),8.57(1H,s)
APCI-MASS:m/z=285(M++1)
以下化合物(制备例288)按照与制备例287相似的方式得到。
制备例288
6-庚基萘-2-羧酸甲酯
NMR(CDCl3,δ):0.88(3H,t,J=6.8Hz),1.17-1.53(6H,
m),1.60-1.82(2H,m),2.79(2H,t,J=7.7Hz),3.97
(3H,s),7.39(1H,dd,J=1.7and8.4Hz),7.64(1H,
s),7.80(1H,d,J=8.6Hz),7.86(1H,d,J=8.4Hz),
8.03(1H,dd,J=1.7和8.6Hz),8.57(1H,s)
APCI-MASS:m/z=271(M+1)
制备例289
在-40℃和搅拌下向6-羟基萘-2-羧酸甲酯(3.0g)在二氯甲烷(40ml)中的溶液里依次加入二异丙基乙胺(3.9ml)和三氟甲磺酸酐(3.0ml)。在-40℃搅拌20分钟后,将混合物加入到乙酸乙酯和冷水的混合物中。分离出有机层,用盐水洗,用硫酸镁干燥,真空干燥。将残余物加到哌啶(20ml)中,向该溶液里加入1-庚炔(4.0ml)和四(三苯膦)钯(0)(0.5g)。在氮气氛下于85℃加热1小时后,将反应混合物减压蒸发。残余物用乙酸乙酯稀释,溶液依次用盐酸和盐水洗,用硫酸镁干燥,减压蒸发。残余物在硅胶(200ml)层析,用正己烷和乙酸乙酯的(9∶1,v/v)混合物洗脱,得到6-(1-庚炔基)萘-2-羧酸甲酯(4.01g)。
NMR(CDCl3,δ):0.94(3H,t,J=7.1Hz),1.30-1.70(6H,
m),2.46(2H,t,J=7.0Hz),3.97(3H,s),7.50(1H,
dd,J=1.7和8.6Hz),7.80(1H,d,J=8.6Hz),7.86
(1H,d,J=8.6Hz),8.04(1H,dd,J=1.7和8.6Hz),
8.55(1H,s)
APCI-MASS:m/z=281(M++1)
以下化合物按照与制备例289相似的方式得到。
制备例290
6-(1-己炔基)萘-2-羧酸甲酯
NMR(CDCl3,δ):0.97(3H,t,J=7.1Hz),1.40-1.71(4H,
m),2.47(2H,t,J=6.8Hz),3.98(3H,s),7.50(1H,
dd,J=1.5和8.5Hz),7.79(1H,d,J=8.6Hz),7.85
(1H,d,J=8.5Hz),7.92(1H,s),8.04(1H,dd,J=1.7
和8.6Hz),8.55(1H,s)
APCI-MASS:m/z=267(M++1)
制备例291
向4-辛基苯胺(5ml)在吡啶(12.5ml)与氯仿(40ml)的混合物中的溶液里加入氯甲酸苯酯(2.95ml),在环境温度下搅拌1.5小时。将反应混合物加到水和乙酸乙酯的混合物中。分出有机层,用硫酸镁干燥。滤除硫酸镁,将滤液减压蒸发,得到4-辛基-N-苯氧羰基苯胺(4.51g)。
IR(KBr):3318.9,1714.4,1234.2cm-1
NMR(CDCl3,δ):0.88(3H,t,J=6.2Hz),1.2-1.4(10H,
m),1.5-1.7(2H,m),2.57(2H,t,J=7.3Hz),6.88
(1H,s),7.1-7.5(9H,m)
以下化合物(制备例292至299)按照与制备例291相似的方式得到。
制备例292
4-(4-叔丁氧羰基哌嗪-1-基)-N-苯氧羰基苯胺
IR(KBr):3309.2,1743.3,1658.5.1197.6cm-1
NMR(CDCl3,δ):1.48(9H,s),3.08(4H,t,J=5.3Hz),
3.58(4H,t,J=5.3Hz),6.87(1H,s),6.91(2H,d,
J=9Hz),7.1-7.5(7H,m)
APCI-MASS:m/z=398(M+H+)
制备例293
1-(4-环己基苯甲酰)-2-(4-甲氧羰基苯甲酰)肼
IR(KBr):3236,2925,2852,1726,1679,1637,1278,
1110cm-1
NMR(DMSO-d6,δ):1.1-1.5(5H,m),1.6-2.0(5H,m),
2.60(1H,m),3.90 (3H,s),7.37(2H,d,J=8.0Hz),
7.85(2H,d,J=8.0Hz),8.0-8.2(4H,m),10.48(1H,
s),10.68(1H,s)
APCI-MASS:m/z=381(M+H)+
制备例294
1-〔4-(哌啶-1-基)苯甲酰〕-2-(4-甲氧羰基苯甲酰)肼
IR(KBr):3500,328 6,2941,2854,1712,1689,1650,
1606,1286,1242cm-1
NMR(DMSO-d6,δ):1.59(6H,s),3.33(4H,s),3.90
(3H,s),6.97(2H,d,J=8.8Hz),7.79(2H,d,
J=8.8Hz),8.02(2H,d,J=8.4Hz),8.09(2H,d,
J=8.4Hz),10.23(1H,s),10.57(1H,s)
APCI-MASS:m/z=382(M+H)+
制备例295
1-〔4-(4-正丙氧基苯基)苯甲酰〕-2-(4-甲氧羰基苯甲酰)肼
IR(KBr):3230,1724,1679,1654,1280,1108cm-1
NMR(DMSO-d6,δ):1.00 3H,d,J=7.5Hz),1.76(2H,tq,
J=6.5and7.5Hz),3.91(3H,s),7.05(2H,d,
J=8.7Hz),7.71(2H,d,J=8.7Hz),7.79(2H,d,
J=8.5Hz),8.00(2H,d,J=8.5Hz),8.05(2H,d,
J=8.6Hz),8.11(2H,d,J=8.6Hz),10.60(1H,s),
10.72(1H,s)
APCI-MASS:m/z=433(M+H)+
制备例296
1-(4-甲氧羰基苯甲酰)-2-癸酰肼
IR(KBr):3220,2919,2850,1724,1643,1600,1567,
1479,1284cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.8Hz),1.2-1.7
(14H,m),2.18(2H,t,J=7.4Hz),3.89(3H,s),7.97
(2H,d,J=8.5Hz),8.06 (2H,d,J=8.5Hz),9.15(1H,
s),10.49(1H,s)
APCI-MASS:m/z=349(M+H+)
制备例297
1-(4-甲氧羰基苯甲酰)-2-(反-4-正戊基环己基羰基)肼
IR(KBr):3201,2923,2852,1727,1600,1567,1479,
1282cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.9Hz),0.9-1.0(2H,
m),1.1-1.5(11H,m),1.7-1.9(4H,m),2.20(1H,
m),3.88(3H,s),7.97(2H,d,J=8.6Hz),8.06(2H,
d,J=8.6Hz),9.85(1H,s),10.46(1H,s)
APCI-MASS:m/z=375(M+H+)
制备例298
1-〔4-(8-甲氧辛氧基)苯甲酰〕-2-(4-甲氧羰基苯甲酰)肼
IR(KBr):3213,2935,2856,1718,1600,1567,1465,
1282cm-1
NMR(DMSO-d6,δ):1.2-1.8(12H,m),3.21(3H,s),
3.29(2H,t,J=6.4Hz),3.90(3H,s),4.04(2H,t,
J=6.5Hz),7.04(2H,d,J=8.8Hz),7.90(2H,d,
J=8.8Hz),8.04(2H,d,J=8.7Hz),8.10(2H,d,
J=8.7Hz),10.41(1H,s),10.64(1H,s)
APCI-MASS:m/z=457(M+H+)
制备例299
1-(4-辛氧基苯甲酰)-2-(4-甲氧羰基苯甲酰)肼
IR(KBr):3224,2923,2854,1724,1681,1643,1502,
1434,1282,1253,1106cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.8Hz),1.2-1.5
(10H,m),1.6-1.8(2H,m),3.89(3H,s),4.04(2H,
t,J=6.3Hz),7.04(2H,d,J=8.7Hz),7.90(2H,d,
J=8.7Hz),8.03(2H,d,J=8.6Hz),8.10(2H,d,
J=8.6Hz),10.42(1H,s),10.64(1H,s)
APCI-MASS:m/z=427(M+H+)
制备例300
将4-正己氧基苯甲酸甲酯(2.00g)和水合肼(4.24g)在乙醇(10ml)中的溶液回流6小时。冷却后将反应混合物倒入水中。过滤收集沉淀物,用水洗,在减压下用P2O5干燥,得到N-(4-正己氧基苯甲酰)肼(1.96g)
IR(KBr):3311,2954,2869,1623,1253cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.8Hz),1.2-1.5(6H,
m),1.6-1.8(2H,m),4.00(2H,t,J=6.5Hz),4.40
(2H,s),6.95(2H,d,J=8.6Hz),7.77(2H,d,
J=8.6Hz),9.59(1H,s)
APCI-MASS:m/z=237(M+H)+
以下化合物(制备例301至308)按照与制备例300相似的方式得到。
制备例301
N-(4-辛基苯基)N’-氨基脲
IR(KBr):3309.2,1683.6,1554.3cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.7Hz),1.1-1.4
(10H,m),1.4-1.6(2H,m),2.48(2H,t,J=8.9Hz),
4.32(2H,s),7.03(2H,d,J=8.4Hz),7.32(1H,s),
7.38(2H,d,J=8.4Hz),8.50(1H,s)
制备例302
N-〔4-(4-叔丁氧羰基哌嗪-1-基)苯基〕-N’-氨基脲
IR(KBr):3237.9,1695.1,1670.1,1540.8,1230.4cm-1
NMR(DMSO-d6,δ):1.42(9H,s),2.97(4H,t,
J=4.9Hz),3.44(4H,t,J=4.9Hz),4.30(2H,s),6.85
(2H,d,J=9.0Hz),7.26(1H,s),7.36(2H,d,
J=9.0Hz),8.41(1H,s)
制备例303
4-环己基苯甲酰肼
IR(KBr):3318,2925,2852,1625,1606,1527,
1326cm-1
NMR (DMSO-d6,δ):1.1-1.5(5H,m),1.6-2.0(5H,m),
2.4-2.6(1H,m),4.44(2H,s),7.27(2H,d,
J=8.2Hz),7.73(2H,d,J=8.2Hz),9.66(1H,s)
APCI-MASS:m/z=219(M+H)+
制备例304
4-(哌啶-1-基)苯甲酰肼
IR(KBr):3263,2852,1612,1504,1245,1124cm-1
NMR(DMSO-d6,δ):1.57(6H,s),3.25(4H,s),4.35
(2H,s),6.90(2H,d,J=9.0Hz),7.68(2H,d,
J=9.0Hz),9.44(1H,s)
APCI-MASS:m/z=220 (M+H)+
制备例305
4-(4-正丙氧基苯基)苯甲酰肼
IR(KBr):3350,3276,1610,1494,1288,978cm-1
NMR(DMSO-d3,δ):0.99(3H,t,J=7.5Hz),1.75(2H,
tq,J=6.5and7.5Hz),3.98(2H,t,J=6.5Hz),4.50
(2H,s),7.03(2H,d,J=8.8Hz),7.65(2H,d,
J=8.8Hz),7.69(2H,d,J=8.4Hz),7.88(2H,d,
J=8.4Hz),9.79(1H,s)
APCI-MASS:m/z=271(M+H+)
制备例306
4-甲氧羰基苯甲酰肼
IR(KBr):3322,3250,3018,1727,1658,1621,1565,
1432,1280,1110cm-1
NMR(DMSO-d6,δ):3.87(3H,s),4.58(2H,s),7.93
(2H,dd,J=8.6和3.1Hz),7.02(2H,dd,J=8.6和
3.1Hz),9.97(1H,s)
APCI-MASS:m/z=195(M+H+)
制备例307
反-4-正戊基环己基羰基肼
IR(KBr):3303,3199,2954,2925,2850,1639,1619,
1533,1457cm-1
NMR(DMSO-d6,δ):0.8-1.0(6H,m),1.1-1.5(10H,m),
1.6-2.2(5H,m),4.10(2H,s ),8.85(1H,s)
APCI-MASS:m/z=213(M+H+)
制备例308
4-(8-甲氧辛氧基)苯甲酰肼
IR(KBr):3309,2937,2852,1606,1494,1253cm-1
NMR(DMSO-d6,δ):1.2-1.8(12H,m),3.20(3H,s),
3.25(2H,t,J=6.5Hz),3.99(2H,t,J=6.5Hz),4.39
(2H,s),6.95(2H,d,J=8.8Hz),7.77(2H,d,
J=8.8Hz),9.58(1H,s)
APCI-MASS:m/z=295(M+H)+
制备例309
在-78℃和搅拌下向4-溴-4’-正庚基联苯(2.71g)在四氢呋喃(100ml)中的溶液里逐滴加入正丁基锂在乙醚和正己烷的混合物中的溶液(1.6M,5.1ml)。在-78℃搅拌30分钟后,将所形成的混合物在-78℃加到草酸二乙酯(3.4ml)在四氢呋喃(50ml)中的溶液里。将所形成的混合物温热至0℃约1小时,向其中加入乙酸(0.5ml)。蒸发得到残余物,将其加入到水和乙酸乙酯的混合物中。分离出有机层,用盐水洗,用硫酸镁干燥。蒸发得到残余物,将其在200ml硅胶上层析,用正己烷和乙酸乙酯的(10∶0-95∶5,v/v)混合物洗脱,得到1-乙基-2-(4-正庚基苯基)乙二酮(2.23g)。
NMR(CDCl3,δ):0.88(3H,t,J=6.6Hz),1.10-1.50(8H,
m),1.44(3H,t,J=7.1Hz),1.50-1.80(2H,m),2.66
(2H,t,J=7.7Hz),4.47(2H,q,J=7.1Hz),7.20-7.40
(2H,m),7.50-7.64(2H,m),7.64-7.85(2H,m),
8.00-8.20(2H,m)
APCI-MASS:m/z=353 (M++1)
制备例310
在环境温度下向氢化钠(60%油分散体,0.37g)在四氢呋喃(40ml)中的悬浮液里分批加入4-乙酰基-4’-正庚基联苯(2.50g)。在室温下搅拌1小时后,向溶液中加入膦酰乙酸三乙酯(1.9ml),将混合物加热回流5小时。在冷却至环境温度之后,向混合物中加入乙酸(0.53ml)并蒸发之。残余物加到水和乙酸乙酯的混合物中。分离出的有机层用盐水洗,用硫酸镁干燥,蒸发。残余物在硅胶(200ml)上层析,用正己烷和二异丙醚的混合物(99∶1-20∶1,v/v)洗脱,得到(E)-3-〔4-(4-庚基苯基)苯基〕-2-丁烯酸乙酯(2.19g)
NMR(CDCl3,δ):0.88(3H,t,J=6.6Hz),1.13-1.48(8H,
m),1.48-1.78(2H,m),2.61(3H,s),2.65(2H,t,
J=7.4Hz),4.22(2H,q,J=7.1Hz),6.20(1H,t,
J=2.7Hz),7.23-7.2 8(2H,m),7.50-7.63(6H,m)
APCI-MASS:m/z=365(M++1)
制备例311
在-60℃向4-溴-4’-正庚基联苯(5.1g)的四氢呋喃(60ml)溶液中加入正丁基锂在正己烷和乙醚的混合物中的溶液(1.6M,9.7ml)。在-60℃搅拌30分钟后,向该混合物中加入N,N-二甲基乙酰胺(4.3ml),将反应混合物温热至0℃。将反应混合物加入到冷水和乙酸乙酯的混合物中,用1N盐酸将pH调节至约1。分离出有机层,用盐水洗,用硫酸镁干燥,蒸发。残余物在硅胶(150ml)上层析,用正己烷和乙酸乙酯的混合物(20∶1,v/v)洗脱,得到4-乙酰基-4’-正庚基联苯(1.60g)。
NMR(CDCl3,δ):0.89(3H,t,J=6.6Hz),1.05-1.48(8H,
m),1.48-1.75(2H,m),2.65(2H,t,J=7.6Hz),2.63
(3H,s),7.20-7.31(2H,m),7.52-7.58(2H,m),
7.65-7.70(2H,m),7.97-8.05(2H,m)
APCI-MASS:m/z=295(M+1)
制备例312
向4-〔4-(8-羟基辛氧基)苯基〕苯甲酸甲酯(500mg)和二羟基吡喃(141mg)在二氯甲烷(15ml)中的溶液里加入对甲苯磺酸(5ml)。将混合物在环境温度下搅拌10分钟,用二氯甲烷稀释,用水和盐水洗。分离出的有机层用硫酸镁干燥,减压蒸发,得到4-〔4-(8-四羟基吡喃-2-基氧基辛氧基)苯基〕苯甲酸甲酯(616mg)。
IR(KBr):2935,2856,1722,1602,1438,1290,
1199cm-1
NMR(CDCl3,δ):1.3-2.0(18H,m),3.3-3.9(4H,m),
3.93(3H,s),4.00(2H,t,J=6.5Hz),4.5-4.6(1H,
m),6.98(2H,d,J=8.7Hz),7.56(2H,d,J=8.7Hz),
7.62(2H,d,J=8.3Hz),8.07(2H,d,J=8.3Hz)
制备例313
在0℃向四氢化钛(11.6g)在二氯甲烷(100ml)中的溶液里逐滴加入4-正戊氧基苯乙酮(10.3g)和4-甲酰苯甲酸甲酯(8.21g)在二氯甲烷(50ml)中的溶液。向该混合物中加入三乙胺(11.15ml)在二氯甲烷(30ml)中的溶液。在0℃搅拌该混合物30分钟,用正己烷稀释。有机层用水洗四次,用盐水洗,在硫酸镁上干燥。减压去除溶剂,残余物与异丙醚一起研磨。过滤收集固体,干燥后得到1-(4-甲氧羰基苯基)-3-(4-正戊氧基苯基)-1-丙烯-3-酮(4.02g)。
IR(KBr):2950,2910,2863,1718,1654,1606,1274,
1176cm-1
NMR(CDCl3,δ):0.94(3H,t,J=6.9Hz),1.3-1.6(4H,
m),1.8-2.0(2H,m),3.93(3H,s),4.04(2H,t,
J=6.5Hz),6.97(2H,d,J=8.8Hz),7.60(1H,d,
J=15.7Hz),7.68(2H,d,J=8.4Hz),7.80(1H,d,
J=15.7Hz),8.0-8.2(4H,m)
APCI-MASS:m/z=353(M+H+)
制备例314
在0℃向四氯化钛(13.88g)在二氯甲烷(100ml)中的溶液里逐滴加入4-乙酰苯甲酸乙酯(11.53g)和4-正戊氧基苯甲醛(12.69g)在二氯甲烷(50ml)中的溶液。向该混合物中加入在二氯甲烷(30ml)中的三乙胺(12.44ml)。将混合物在0℃搅拌30分钟,用乙酸乙酯稀释。有机层依次用水(四次)和盐水洗,用硫酸镁干燥。减压去除溶剂,残余物用正己烷研制。过滤收集固体,干燥,得到1-(4-正戊氧基苯基)-3-(4-乙氧羰基苯基)-1-丙烯-3-酮(13.45g)。
IR(KBr):2956,2929,2861,1718,1656,1594,1510,
1272cm-1
NMR(CDCl3,δ):0.94(3H,t,J=7.1Hz),1.3-1.9(9H,
m),4.01(2H,t,J=6.5Hz),4.42(2H,q,J=7.1Hz),
6.93(1H,d,J=8.7Hz),7.37(1H,d,J=15.6Hz),7.60
(2H,d,J=8.7Hz),7.81(1H,d,J=15.6Hz),8.03(2H,
d,J=8.5Hz),8.16(2H,d,J=8.5Hz)
APCI-MASS:m/z=367(M+H+)
以下化合物按照与制备例314相似的方式得到。
制备例315
4-氧代-1-(4-正己氧基苯基)哌啶-3-羧酸乙酯。
IR(纯相):1664.3,1511.9,1243.9,1216.9cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.2-1.5(6H,
m),1.32(3H,t,J=7.1Hz),1.65-1.85(2H,m),2.51
(2H,t,J=5.8Hz),3.31(2H,t,J=5.8Hz),3.76(2H,
s),3.91(2H,t,J=6.5Hz),4.26(2H,q,J=7.1Hz),
6.84(2H,d,J=9.2Hz),6.94(2H,d,J=9.2Hz),12.06
(1H,s)
APCI-MASS:m/z=348(M++H)
制备例316
在0℃向4-正己氧基苯甲酰肼(1.96g)和吡啶(0.74ml)在四氢呋喃(20ml)中的溶液里逐滴加入氯化对苯二甲酸单甲酯(1.56g)在四氢呋喃(15ml)中的溶液。在室温下搅拌反应混合物2小时,倒入水中。过滤收集沉淀,用乙腈洗,将残渣减压干燥,得到1-(4-正己氧基苯甲酰)-2-(4-甲氧羰基苯甲酰)肼(2.99g)。
IR(KBr):3230,3023,2954,2858,1724,1681,1643,
1280,1251,1105cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.6Hz),1.2-1.5(6H,
m),1.6-1.8(2H,m),3.90(3H,s),4.04(2H,t,
J=6.4Hz),7.04(2H,d,J=8.7Hz),7.90(2H,d,
J=8.7Hz),8.03(2H,d,J=8.4Hz),8.10(2H,d,
J=8.4Hz),10.42(1H,s),10.65(1H,s)
APCI-MASS:m/z=399(M+H)+
制备例317
将1-(4-正己氧基苯基)-4-哌啶酮(0.823g)、1-(4-乙氧羰基苯基)哌嗪(0.7g)和异丙醇钛(IV)(1.11ml)的混合物在室温下搅拌。1小时后,混合物的红外光谱显示无酮键,用3ml无水乙醇稀释此粘稠溶液。加入氰基硼氢化钠(0.121g),将溶液搅拌3小时。在搅拌下加入3ml水,形成的有机沉淀物过滤,用乙醇洗。滤液用乙酸乙酯萃取。分出有机层,用硫酸镁干燥。滤除硫酸镁,滤液减压蒸发,得到4-〔4-〔1-(4-正己氧基苯基)哌啶-4-基〕哌嗪-1-基〕苯甲酸乙酯(331mg)。
IR(KBr):1708.6,1606.4,1511.9,1284.4,1236.1cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.5Hz),1.2-1.55(6H,
m),1.37(3H,t,J=7.1Hz),1.6-1.85(4H,m),1.95
(2H,d,J=12Hz)-,2.41(1H,m),2.62(2H,d,
J=11Hz),2.75(4H,t,J=5.0Hz),3.35(4H,t,
J=5.0Hz),3.58(2H,d,J=11Hz),3.90(2H,t,
J=6.5Hz),4.32(2H,q,J=7.1Hz),6.7-7.0(6H,m),
7.92(2H,d,J=9.0Hz)
APCI-MASS:m/z=494(M++H)
以下化合物按照与制备例317相似的方式得到。
制备例318
1-叔丁氧羰基-4-(4-苯基环己基)哌嗪
IR(KBr):1697.1,1245.8,1170.6,1124.3,700cm-1
NMR(CDCl3,δ):1.2-1.65(17H,m),1.9-2.1(4H,m),
2.3-2.6(2H,m),2.55(4H,t,J=5.0Hz),3.44(4H,
t,J=5.0Hz),7.1-7.4(5H,m)
APCI-MASS:m/z=345(M++H)
制备例319
向1-(N,N-二甲氨基)-2-(4-乙氧羰基苯甲酰)乙烯(0.742g)和4-正己氧基苯甲脒盐酸盐(0.847g)在甲醇(10ml)中的悬浮液里加入28%甲醇钠在甲醇中的溶液(0.64ml)。将此悬浮液回流6小时,分配在乙酸乙酯和水之中。有机层依次用水和盐水洗,用硫酸镁干燥,减压蒸发。残余物用乙腈研制。过滤收集固体,减压干燥,得到4-〔2-(4-正己氧基苯基)嘧啶-6-基苯甲酸甲酯(0.61g)。
IR(KBr):2931,2861,1722,1606,1558,1251cm-1
NMR(CDCl3,δ):0.95(3H,t,J=6.7Hz),1.2-1.6(6H,
m),1.8-2.0(2H,m),3.97(3H,s),4.05(2H,t,
J=6.5Hz),7.02(2H,d,J=8.8Hz),7.56(1H,d,
J=5.2Hz),8.18(2H,d,J=8.6Hz),8.28(2H,d,
J=8.6Hz),8.52-(2H,d,J=8.8Hz),8.83(1H,d,
J=5.2Hz)
APCI-MASS:m/z=391(M+H+)
制备例320
将1-(4-甲氧羰基苯基)-3-(4-正戊氧基苯基)-1-丙烯-3-酮(4.0g)和盐酸羟胺(3.93g)在乙醇(40ml)中的溶液回流4小时。将混合物用乙酸乙酯稀释,有机层用水洗两次,用盐水洗,用硫酸镁干燥。减压除去溶剂,得到粗品肟。向粗品肟在1,2-二氯乙烷(20ml)中的溶液里加入活化的二氧化锰(IV)(10.0g)。将反应混合物回流2小时,过滤。残渣用二氯甲烷洗。减压去除溶剂,残余物用乙腈研制。过滤收集固体,干燥,得到4-〔3-(4-正戊氧基苯基)异噁唑-5-基〕苯甲酸甲酯(0.98g)。
IR(KBr):2940,2871,1720,1612,1278,1249,1178,
1108cm-1
NMR(DMSO-d6,δ):0.94(3H,t,J=7.2Hz),1.2-1.6(4H,
m),1.7-1.9(2H,m),3.95(3H,s),4.01(2H,t,
J=6.5Hz),6.87(1H,s),6.98(2H,d,J=8.9Hz),7.79
(2H,d,J=8.9Hz),7.89(2H,d,J=8.6Hz),8.15(2H,
d,J=8.6Hz)
APCI-MASS:m/z=366(M+H+)
制备例321
在40℃于2小时内向4-甲氧羰基苯基羟基亚氨基甲基氯(16.98g)和4-正戊氧基苯基乙炔(18.96g)在四氢呋喃(170ml)中的溶液里加入三乙胺(14.4ml)在四氢呋喃(140ml)中的溶液,将混合物在40℃搅拌30分钟。用二氯甲烷稀释该混合物,用水和盐水洗。分离出的有机层用硫酸镁干燥,减压蒸发。残余物与乙腈-起研磨。过滤收集沉淀物,干燥后得到4-〔5-(4-正戊氧基苯基)异噁唑-3-基〕苯甲酸甲酯(24.56g)。
IR(KBr):2942,2873,1716,1616,1508,1280,
1108cm-1
NMR(CDCl3,δ):0.95(3H,t,J=6.9Hz),1.3-1.6(4H,
m),1.8-2.0(2H,m),3.95(3H,s),4.02(2H,t,
J=6.5Hz),6.74(1H,s),6.99(2H,d,J=8.8Hz),7.76
(2H,d,J=8.8Hz),7.93(2H,d,J=8.5Hz),8.14(2H,
d,J=8.5Hz)
APCI-MASS:m/z=366(M+H+)
制备例322
在0℃向N-羟基-4-辛氧基苯甲脒(1.89g)的吡啶(10ml)溶液中逐滴加入氯化对苯二甲酸单甲酯(1.67g)的四氢呋喃(15ml)溶液。在室温下搅拌混合物15分钟,倒入水中。过滤收集沉淀物,干燥后溶在10ml吡啶中,将溶液回流1小时。反应混合物用乙酸乙酯稀释,依次用1N HCl、水和盐水洗。分离出的有机层用硫酸镁干燥,减压去除溶剂。残余物与乙腈一起研磨,过滤收集固体,干燥后得到4-〔3-(4-正己氧基苯基)-1,2,4-噁二唑-5-基〕苯甲酸甲酯(2.27g)。
IR(KBr):2950,2925,2863,1720,1280,1255cm-1
NMR(CDCl3,δ):0.92(3H,t,J=6.6Hz),1.2-1.9(8H,
m),3.97(3H,s),4.03(2H,d,J=6.5Hz),7.00(2H,
d,J=8.9Hz),8.09(2H,d,J=8.9Hz),8.20(2H,d,
J=6.6Hz),8.28(2H,d,J=6.6Hz)
APCI-MASS:m/z=381(M+H)+
制备例323
将1-(4-正己氧基苯甲酰)-2-(4-甲氧羰基苯甲酰)肼(1.00g)在磷酰氯(5ml)中的悬浮液回流1小时。冷却后将溶液减压浓缩。将残余物倒入冰水中用二氯甲烷萃取。有机层依次用水和盐水洗,用硫酸镁干燥。减压除去溶剂,残余物与乙腈一起研磨,过滤收集固体,减压干燥,得到4-〔5-(4-正己氧基苯基)-1,3,4-噁二唑-2-基〕苯甲酸甲酯(761mg)。
IR(KBr):2954,2854,1724,1612,1494,1280,
1249cm-1
NMR(CDCl3,δ):0.91(3H,t,J=6.6Hz),1.3-1.6(6H,
m),1.7-1.9(2H,m),3.96(3H,s),4.04(2H,t,
J=6.5Hz),7.02(2H,d,J=8.6Hz),8.07(2H,d,
J=8.6Hz),8.19(4H,m)
APCI-MASS:m/z=381(M+H)+
以下化合物(制备例324至327)按照与制备例323相似的方式得到。
制备例324
4-〔5-〔4-(4-正丙氧基苯基)苯基〕-1,3,4-噁二唑-2-基〕苯甲酸甲酯
IR(KBr):1720,1614,1496,1280,1103cm-1
NMR(CDCl3,δ):1.07(3H,d,J=7.5Hz),1.84(2H,tq,
J=6.5and7.5Hz),3.98(3H,s),3.99(2H,t,
J=6.5Hz),7.01(2H,d,J=8.8Hz),7.60(2H,d,
J=8.8Hz),7.73(2H,d,J=8.5Hz),8.19(2H,d,
J=8.5Hz),8.22(4H,s)
APCI-MASS:m/z=415(M+H+)
制备例325
4-〔5-(正壬基)-1,3,4-噁二唑-2-基〕苯甲酸甲酯
IR(KBr):2915,2848,1724,1569,1436,1413,
1278cm-1
NMR(CDCl3,δ):0.88(3H,t,J=6.4Hz),1.2-1.6(12H,
m),1.8-2.0(2H,m),2.94(2H,t,J=7.6Hz),3.96
(3H,s),8.11(2H,d,J=8.8Hz),8.17(2H,d,
J=8.8Hz)
APCI-MASS:m/z=331(M+H)+
制备例326
4-〔5-〔4-(8-甲氧辛氧基)苯基〕-1,3,4-噁二唑-2-基〕甲酯
IR(KBr):2925,2858,1722,1614,1280,1259cm-1
NMR(CDCl3,δ):1.3-1.9(12H,m),3.36(3H,s),3.37
(2H,t,J=6.4Hz),3.97(3H,s),4.04(2H,t,
J=6.5Hz),7.02(2H,d,J=8.9Hz),8.07(2H,d,
J=8.9Hz),8.20(4H,s)
APCI-MASS:m/z=439(M+H+)
制备例327
4-〔5-(4-正辛氧基苯基)-1,3,4-噁二唑-2-基]苯甲酸甲酯
IR(KBr):2923,2856,1722,1614,1496,1282,
1103cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.8Hz),1.2-1.6(10H,
m),1.7-1.9(2H,m),3.97(3H,s),4.04(2H,t,
J=6.5Hz),7.03(2H,d,J=8.7Hz),8.07(2H,d,
J=8.7Hz),8.19(4H,m)
APCI-MASS:m/z=409(M+H+)
制备例328
将1-(4-己氧基苯甲酰)-2-(4-甲氧羰基苯甲酰)肼(1.0g)和五硫化二磷(1.28g)在四氢呋喃(15ml)中的悬浮液于室温下搅拌3小时。将混合物用水(30ml)稀释,搅拌30分钟,用二氯甲烷萃取。有机层用盐水洗,用硫酸镁干燥,减压蒸发。残余物与乙腈一起研磨。过滤收集固体,减压干燥,得到4-〔5-(4-正己氧基苯基)-1,3,4-噻二唑-2-基〕苯甲酸甲酯(816mg)。
IR(KBr):2925,2871,1722,1608,1436,1276,
1106cm-1
NMR(CDCl3,δ):0.92(3H,t,J=6.6Hz),1.3-2.0(8H,
m),3.96(3H,s),4.03(2H,t,J=6.5Hz),6.99(2H,
d,J=8.6Hz),7.95(2H,d,J=8.4Hz),8.16(2H,d,
J=8.4Hz)
APCI-MASS:m/z=397(M+H)+
以下化合物(制备例329至334)根据与制备例328相似的方式得到。
制备例329
4-〔5-〔4-(8-甲氧辛氧基)苯基〕-1,3,4-噻二唑-2-基〕苯甲酸甲酯
IR(KBr):3210,2935,2856,1718,1600,1465,1280,
1110cm-1
NMR(CDCl3,δ):1.3-1.6(10H,m),1.7-1.9(2H,m),
3.33(3H,s),3.37(2H,d,J=6.4Hz),3.96(3H,s),
4.03(2H,t,J=6.5Hz),6.99(2H,d,J=8.9Hz),7.94
(2H,d,J=8.9Hz),8.07(2H,d,J=8.6Hz),8.16(2H,
d,J=8.6Hz)
APCI-MASS:m/z=455(M+H+)
制备例330
4-〔5-(4-环己基苯基)-1,3,4-噻二唑-2-基〕
苯甲酸甲酯
IR(KBr):2925,2850,1716,1432,1274,1108,997cm-1
NMR(CDCl3,δ):1.2-1.6(5H,m),1.7-2.0(5H,m),
2.58(1H,m),3.96(3H,s),7.34(2H,d,J=8.2Hz),
7.93(2H,d,J=8.2Hz),8.07(2H,,d,J=8.6Hz),8.16
(2H,d,J=8.6Hz)
APCI-MASS:m/z=379(M+H+)
制备例331
4-〔5-〔4-(哌啶-1-基)苯基〕-1,3,4-噻二唑-2-基〕苯甲酸甲酯
IR(KBr):2940,2848,1720,1602,1436,1415,1276,
1108cm-1
NMR(CDCl3,δ):1.68(6H,br),3.34(4H,br),3.96
(3H,s),6.95(2H,d,J=8.7Hz),7.88(2H,d,
J=8.7Hz),8.05(2H,d,J=8.6Hz),8.16(2H,d,
J=8.6Hz)
APCI-MASS:m/z=380(M+H+)
制备例332
4-〔5-(4-正辛氧基苯基)-1,3,4-噻二唑-2-基〕苯甲酸甲酯
IR(KBr):2927,2858,1720,1606,1434,1276,
1106cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.8Hz),1.2-1.6(10H,
m),1.7-1.9(2H,m),3.96(3H,s),4.03(2H,t,
J=6.5Hz),7.00(2H,d,J=8.9Hz),7.95(2H,d,
J=8.9Hz),8.06(2H,d,J=8.4Hz),8.16(2H,d,
J=8.4Hz)
APCI-MASS:m/z=425(M+H+)
制备例333
4-〔5-(4-正戊基环己基)-1,3,4-噻二唑-2-基〕苯甲酸甲酯
IR(KBr):2923,2850,1722,1440,1276,1110cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.9Hz),1.0-1.8(13H,
m),1.92(2H,d,J=13.4Hz),2.24(2H,d,J=12.2Hz),
3.15(1H,tt,J=12.2和3.5Hz),3.95(3H,s),8.01
(2H,dd,J=8.6和2.0Hz),8.13(2H,dd,J=8.6和
2.0Hz)
APCI-MASS:m/z=373(M+H+)
制备例334
4-〔5-〔4-(4-正戊氧基苯基)苯基〕-1,3,4-噻二唑-2-基〕苯甲酸甲酯
IR(KBr):1720,1540,1508,1282cm-1
NMR(CDCl3,δ):1.07(3H,t,J=7.5Hz),1.85(2H,m),
3.9-4.1(5H,m),7.01(2H,d,J=8.8Hz),7.59(2H,
d,J=8.8Hz),7.70(2H,d,J=8.4Hz)8.07(2H,d,
J=8.4Hz),8.1-8.2(4H,m)
APCI-MASS:m/z=431(M+H)+
制备例335
向4-己氧基苯甲酸在草酰氯(10ml)和二氯甲烷(10ml)中的悬浮液里加入N,N-二甲基甲酰胺(0.1ml)。在室温下搅拌混合物2小时。减压去除溶剂,得到粗制的4-己氧基苯甲酰氯。在10℃向3-氨基-4-羟基苯甲酸乙酯(733mg)、三乙胺(1.38ml)和4-二甲氨基吡啶(DMAP,10mg)在二氯甲烷(10ml)中的悬浮液里逐滴加入上面得到的4-己氧基苯甲酰氯在二氯甲烷(5ml)中的溶液。将反应混合物在10℃搅拌1.5小时,用二氯甲烷(20ml)稀释。溶液依次用H2O(20ml)、1N盐酸(20ml×2)、H2O(20ml)和盐水(20ml)洗。有机层用MgSO4干燥,减压去除溶剂。向残余物中加入甲苯(15ml)和对甲苯磺酸(10mg)。将混合物回流6小时,减压去除溶剂。残余物与乙腈一起研磨,过滤收集沉淀,用PO5干燥,得到2-(4-己氧基苯基)-5-乙氧羰基苯并噁唑(0.60g)。
IR(KBr):2952,2871,1712,1623,1500,1294,
1255cm-1
NMR(CDCl3,δ):0.92(3H,t,J=6.6Hz),1.3-1.6(9H,
m),1.7-1.9(2H,m),4.05(2H,t,J=6.5Hz),4.42
(2H,q,J=7.1Hz),7.03(2H,d,J=6.9Hz),7.57(1H,
d,J=8.6Hz),8.08(1H,dd,J=8.6和1.7Hz),8.18
(2H,d,J=6.9Hz),8.43(1H,d,J=1.7Hz)
APCI-MASS:m/z=368(M+H+)
以下化合物(制备例336至337)按照与制备例335相似的方式得到。
制备例336
5-乙氧羰基-2-(2-辛氧基吡啶-5-基)苯并噁唑
IR(KBr):2933,2858,1716,1623,1604,1577,1467,
1290,1213,1083cm-1
NMR(CDCl3,δ):0.89(3H,t,J=6.7Hz),1.2-1.5(10H,
m),1.43(3H,t,J=7.1Hz),1.7-1.9(2H,m),4.3-4.5
(4H,m),6.87(1H,d,J=8.7Hz),7.60(1H,d,
J=8.6Hz),8.11(1H,dd,J=8.6和1.6Hz),8.37(1H,
dd,J=8.8和2.4Hz),8.45(1H,d,J=1.6Hz),9.03
(1H,d,J=2.4Hz)
APCI-MASS:m/z=397(M+H+)
制备例337
2-〔4-(4-己基苯基)苯基〕-5-乙氧羰基苯并噁唑
IR(KBr):2952,2871,1712,1623,1500,1294,1255,
1024cm-1
NMR(CDCl3,δ):0.90(3H,t,J=6.6Hz),1.2-1.5(6H,
m),1.44(3H,t,J=7.1Hz),1.6-1.8(2H,m),2.67
(2H,t,J=7.3Hz),4.43(2H,q,J=7.1Hz),7.27(1H,
d,J=3.7Hz),7.32(1H,s),7.5-7.7(3H,m),7.77
(2H,d,J=8.6Hz),8.12(1H,dd,J=8.6and1.7Hz),
8.32(2H,d,J=8.5Hz),8.48(1H,d,J=1.2Hz)
APCI-MASS:m/z=428(M+H+)
制备例338
将4-〔4-(8-溴代辛氧基)苯基〕苯甲酸(1g)在2,6-二甲基吗啉(3.06ml)中的悬浮液回流30分钟。将反应混合物加到水和乙酸乙酯的混合物中,用浓HCl调节至pH2.0。分出有机层,用硫酸镁干燥。滤除硫酸镁,将滤液减压蒸发,得到4-〔4-〔8-(2,6-二甲基吗啉-4-基)辛氧基〕苯基〕苯甲酸盐酸盐(0.95g)。
IR(KBr):2939.0,1704.8,1606.4,1189.9cm-1
NMR(DMSO-d6,δ):1.12(6H,d,J=6.3Hz),1.2-1.6
(10H,m),1.6-1.9(4H,m),2.4-2.7(2H,m),2.9-3.1
(2H,m),3.8-4.0(2H,m),4.02(2H,t,J=6.3Hz),
7.04(2H,d,J=8.8Hz),7.68(2H,d,J=8.8Hz),7.75
(2H,d,J=8.4Hz),7.99(2H,d,J=8.4Hz)
APCI-MASS:m/z=440(M+H+)
制备例339
将氢化钠(60%矿物油悬浮液,108mg)加到乙氧基乙醇(10ml)中,将溶液在60℃搅拌20分钟。向此溶液中加入4-〔4-(8-溴代辛氧基)苯基〕苯甲酸甲酯(1.26g),在70℃搅拌反应混合物2小时。向反应混合物中加入10%氢氧化钠水溶液(2.4ml),在70℃搅拌该溶液1小时。冷却后用1N盐酸将溶液调至pH2.0。过滤收集沉淀,干燥,得到4-〔4-〔8-(2-乙氧乙氧基)辛氧基〕苯基〕苯甲酸(1.13g)。
IR(KBr):2933,2858,1685,1604,1434,1294,
1132cm-1
NMR(DMSO-d6,δ):1.09(3H,t,J=7.0Hz),1.2-1.9
(14H,m),3.2-3.6(6H,m),4.01(2H,d,J=6.3Hz),
7.04(2H,d,J=8.8Hz),7.67(2H,d,J=8.8Hz),7.74
(2H,d,J=8.5Hz),7.98(2H,d,J=8.5Hz)
APCI-MASS:m/z=415(M+H+)
以下化合物按照与制备例300相似的方式得到。
制备例340
4-正戊氧基苯甲酰肼
IR(KBr):3182,2937,2869,1645,1618,1571,
1251cm-1
NMR(DMSO-d6,δ):0.89(3H,d,J=7.1Mz),1.2-1.8(6H,
m),4.00(2H,t,J=6.5Hz),4.41(2H,s),6.96(2H,
d,J=8.8Hz),7.78(2H,d,J=8.8Hz),9.59(1H,s)
APCI-MASS:m/z=223(M+H+)
以下化合物根据与制备例291相似的方式得到。
制备例341
1-(4-甲氧羰基苯甲酰)-2-(4-正戊氧基苯甲酰)肼
IR(KBr):3234,2956,2931,1724,1683,1643,1610,
1284,1253cm-1
NMR(DMSO-d6,δ):0.90(3H,t,J=6.9Hz),1.2-1.5(4H,
m),1.6-1.8(2H,m),3.90(3H,s),4.04(2H,t,
J=6.5Hz),7.04(2H,d,J=8.8Hz),7.90(2H,d,
J=8.8Hz),8.03(2H,d,J=8.7Hz),8.10(2H,d,
J=8.7Hz),10.42(1H,s),10.64(1H,s)
APCI-MASS:m/z=385(M+H+)
以下化合物按照与制备例328相似的方式得到。
制备例342
4-〔5-(4-正戊氧基苯基)噻二唑-2-基〕苯甲酸甲酯
IR(KBr):2940,2871,1720,1606,1438,1280cm-1
NMR(CDCl3,δ):0.95(3H,t,J=7.1Hz),1.3-1.6(4H,
m),1.8-2.0(2H,m),3.96(3H,s),4.03(2H,t,
J=6.5Hz),6.99(2H,d,J=8.8Hz),7.94(2H,d,
J=8.8Hz),8.06(2H,d,J=8.7Hz),8.16(2H,d,
J=8.7Hz)
APCI-MASS:m/z=383(M+H+)
以下化合物按照与制备例32相似的方式得到。
制备例343
4-〔5-(4-正戊氧基苯基)噻二唑-2-基〕苯甲酸
IR(KBr):2954,2867,1687,1602,1432,1294,
1255cm-1
NMR(DMSO-d6,δ):0.91(3H,t,J=7.0Hz),1.3-1.5(4H,
m),1.7-1.9(2H,m),4.07(2H,t,J=6.7Hz),7.13
(2H,d,J=8.8Hz),7.97(2H,d,J=8.8Hz),8.07(4H,
s)
APCI-MASS:m/z=369(M+H+)
以下化合物按照与制备例49相似的方式得到。
制备例344
1-〔4-〔5-(4-正戊氧基苯基)噻二唑-2-基〕苯甲酰〕苯并三唑3-氧化物
IR(KBr):2948,2873,1770,1602,1257,1232cm-1
NMR(CDCl3,δ):0.95(3H,t,J=7.1Hz),1.3-1.6(4H,
m),1.8-2.0(2H,m),4.04(2H,t,J=6.5Hz),7.01
(2H,d,J=8.1Hz),7.4-7.7(3H,m),7.97(2H,d,
J=8.1Hz),8.12(1H,d,J=8.2Hz),8.24(2H,d,
J=8.0Hz),8.40(2H,d,J=8.0Hz)
APCI-MASS:m/z=486(M+H+)
制备例345
在40℃向氯化4-溴苯甲醛肟(647mg)和4-正戊氧基-苯基乙炔(650mg)在四氢呋喃(7ml)中的溶液里逐滴加入三乙胺(0.5ml)在四氢呋喃(5ml)中的溶液。将溶液在40℃搅拌30分钟,倒入水中,用乙酸乙酯萃取。有机层依次用水和盐水洗,用硫酸镁干燥。减压蒸走溶剂,残余物与乙腈一起研磨。过滤收集沉淀,干燥,得到4-〔5-(4-正戊氧基苯基)异噁唑-3-基〕溴苯(0.59g)。
IR(KBr):2948,2867,1612,1430,1255cm-1
NMR(CDCl3,δ):0.95(3H,t,J=6.9Hz),1.3-1.6(4H,
m),1.7-1.9(2H,m),4.01(2H,t,J=6.5Hz),6.66
(1H,s),6.98(2H,d,J=8.8Hz),7.60(2H,d,
J=8.6Hz),7.7-7.9(4H,m)
APCI-MASS:m/z=388(M+H+)
制备例346
在-40℃和N2气流下向4-〔5-(4-正戊氧基苯基)异噁唑-3-基〕溴苯(386mg)在四氢呋喃(5ml)中的悬浮液中加入1.55M的正丁基锂在己烷(0.84ml)中的溶液,将溶液在-40℃搅拌1小时。向此溶液中加入1g碎干冰,在-40℃搅拌悬浮液1小时。将悬浮液用水稀释,用1N盐酸酸化。过滤收集沉淀物,干燥,得到4-〔5-(4-正戊氧基苯基)异戊唑-3-基〕苯甲酸(312mg)。
IR(KBr):2939,2867,1681,1614,1429,1255,1178,
821cm-1
NMR(DMSO-d6,δ):0.91(3H,t,J=7.1Hz),1.3-1.5(4H,
m),1.6-1.8(2H,m),4.04(2H,t,J=6.5Hz),7.11
(2H,d,J=8.9Hz),7.54(1H,s),7.85(2H,d,
J=8.9Hz),7.98(2H,d,J=8.6Hz),8.11(2H,d,
J=8.6Hz)
APCI-MASS:m/z=352(M+H+)
在下列实施例1-117中的起始化合物和实施例1-122和124中的目标化合物(1)至(122)和(124)用以下的化学式示例说明。起始化合物(实施例1至117中相同)
目标化合物(1)至(122)和(124)
在以下实施例中,目标化合物(X)〔例如目标化合物(1)〕是指实施例(X)〔例如实施例(1)〕中的目标化合物。
实施例1
向起始化合物(1g)和1-(6-辛基-氧甲基吡啶甲酰)苯并三唑3-氧化物(0.399g)在N,N-二甲基甲酰胺(10ml)中的溶液里加入4-(N,N-二甲氨基)吡啶(0.140g),在环境温度下搅拌12小时。将反应混合物与乙酸乙酯一起研磨。过滤收集沉淀物,减压干燥。将粉末溶于水中,在离子交换树脂柱(DOWEX-50WX4,商品名称,Dow化学公司制备)上柱色谱,用水洗脱。将含有目标化合物的级分合并,在ODS(YMC-凝胶ODS-AM·S-50,商品名称,Yamamura化学实验室制备)上进行柱色谱,用50%甲醇水溶液洗脱。将含有目标化合物的级分合并,减压蒸发除掉甲醇。残余物冷冻干燥,得到目标化合物(1)。
IR(KBr):3347,1664,1629,1517cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.7Hz),0.98(3H,
d,J=6.7Hz),1.09(3H,d,J=6.0Hz),1.2-1.47
(10H,m),1.47-1.67(2H,m),1.67-2.06(3H,m),
2.06-2.5(4H,m),3.19(1H,m),3.53(2H,t,
J=6.4Hz),3.5-3.85(2H,m),3.85-4.7(13H,m),
5.35(11H,m),5.56(1H,d,J=5.7Hz),6.73(1H,
d,J=8.3Hz),6.83(1H,d,J=8.3Hz),6.89(1H,
s),7.05(1H,s),7.11(1H,s),7.32(1H,m),
7.43(1H,d,J=8.5Hz),7.63(1H,d,J=7.3Hz),
7.85-8.13(4H,m),8.66(1H,d,J=7.8Hz),8.84
(1H,s)
FAB-MASS(快原子轰击质谱):m/z=1228(M++Na)
元素分析 理论值C50H72N9O22SNa·6H2O:
C45.49,H6.44,N9.59
实验值:C45.89,H6.52,N9.69
目标化合物(2)至(25)按照与实施例1相似的方式得到。
实施例2
IR(KBr):3353,1666,1510,1236cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.7Hz),0.96(3H,
d,J=6.7Hz),1.06 (3H,d,J=5.8Hz),1.2-1.5
(10H,m),1.55-2.05(5H,m),2.11-2.7(4H,m),
3.0-3.3(5H,m),3.3-3.5(4H,m),3.6-4.5(15H,
m),4.6-5.6(12H,m),6.6-7.2(10H,m),7.2-7.5
(3H,m),7.81(2H,d,J=8.8Hz),8.05(1H,d,
J=8.7Hz),8.28(1H,d,J=8.7Hz),8.41(1H,d,
J=6.7Hz),8.84(1H,s)
FAB-MASS(快原子轰击质谱):m/z=1373(M++Na)
元素分析 理论值C60H83N10O22SNa·4H2O:
C50.63,H6.44,N9.84
实验值:C50.59,H6.59,N9.79
实施例3
IR(KBr):3350,1664,1627,1047cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.6Hz),1.08(3H,
d,J=5.7Hz),1.15-1.53(8H,m),1.55-2.1(9H,
m),2.1-2.45(3H,m),2.5-2.7(1H,m),3.18(1H,
m),3.6-3.83(2H,m),3.83-4.6(17H,m),4.7-5.4
(11H,m),5.51(1H,d,J=5.9Hz),6.73(1H,d,
J=8.2Hz),6.83(1H,d,J=8.2Hz),6.85(1H,s),
7.03(2H,d,J=8.4Hz),7.05(1H,s),7.30(1H,
s),7.2-7.5(2H,m),7.67(2H,d,J=8.4Hz),7.71
(2H,d,J=7.4Hz),7.94(1H,s),7.96(2H,d,
J=7.4Hz),8.06(1H,d,J=8.0Hz),8.25(1H,d,
J=6.7Hz),8.50(1H,s),8.74(1H,d,J=6.7Hz),
8.84(1H,s)
FAB-MASS:m/z=1356(M++Na)
元素分析 理论值C58H76N11O22SNa·4H2O:
C49.53,H6.02,N10.95
实验值:C49.26,H6.22,N10.77
实施例4
IR(KBr):3350,1660,1631,1047cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.9Hz),0.97(3H,
d,J=6.6Hz),1.09(3H,d,J=5.3Hz),1.2-1.5
(10H,m),1.37(6H,s),1.55-2.0(5H,m),2.1-
2.6(4H,m),3.16(1H,m),3.73(2H,m),3.89
(2H,t,J=6.3Hz),3.95-4.49(11H,m),4.68-5.21
(10H,m),5.25(1H,d,J=4.1Hz),5.53(1H,d,
J=5.7Hz),6.73(1H,d,J=8.2Hz),6.75-6.85(4H,
m),6.91(1H,d,J=8.2Hz),7.05(1H,s),7.15
(1H,s),7.3-7.5(2H,m),7.9-8.2(3H,m),8.84
(1H,s)
FAB-MASS:m/z=1271(M++Na)
元素分析 理论值C53H77N8O23SNa·4H2O:
C48.18,H6.48,N8.48
实验值:C48.04,H6.51,N8.38
实施例5
IR(KBr):1666,1629,1222cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.6Hz),0.9-1.12
(6H,m),1.12-1.52(13H,m),1.52-1.93(5H,m),
2.08-2.55(4H,m),3.16(1H,m),3.6-5.3(26H,
m),5.49+5.54(1H,d,J=5.8Hz,非对映体混合物
),6.60-7.1(7H,m),7.04(1H,s),
7.1(1H,m),7.2-7.5(2H,m),7.9-8.43(3H,m),
8.83(1H,s)
FAB-MASS:m/z=1257(M++Na)
元素分析 理论值C52H75N8O23SNa·3H2O:
C48.44,H6.33,N8.69
实验值:C48.16,H6.51,N8.53
实施例6
IR(KBr):3349,1666,1629,1259cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.7Hz),0.9(3H,
d,J=5.7Hz),0.96(3H,d,J=6.7Hz),1.1-1.55
(19H,m),1.55-2.0(5H,m),2.0-2.47(4H,m),
2.65-3.25(3H,m),3.5-5.13(27H,m),5.17(1H,
d,J=3.2Hz),5.24(1H,d,J=4.5Hz),5.38(1H,d,
J=5.9Hz),6.5-6.9(5H,m),6.9-7.1(3H,m),7.2-
7.46(2H,m),7.7-8.1(3H,m),8.83(1H,s)
FAB-MASS:m/z=1368(M++Na)
元素分析 理论值C58H84N9O24SNa·5H2O:
C48.50,N6.60,N8.78
实验值:C48.47,H6.83,N8.78
实施例7
IR(KBr):3350,1666,1502,1199cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.6Hz),0.97(3H,
d,J=6.7Hz),1.06(3H,d,J=5.7Hz),1.2-1.5
(10H,m),1.55-2.0(5H,m),2.1-2.6(4H,m),
3.17(1H,m),3.7-4.5 (15H,m),4.7-5.22(10H,
m),5.24(1H,d,J=4.4Hz),5.60(1H,d,
J=5.9Hz),6.68-7.03(8H,m),7.04(1H,s),7.2-
7.42(2H,m),7.85-8.1(3H,m),8.83(1H,s)
FAB-MASS:m/z=1229(M++Na)
元素分析 理论值C50H71N8O23SNa·5H2O:
C46.29,H6.29,N8.64
实验值:C46.39,H6.05,N8.72
实施例8
IR(KBr):3350,1666,1631,1513cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.2Hz),0.97(3H,
d,J=6.7Hz),1.04(3H,d,J=5.7Hz),1.2-1.58
(8H,m),1.58-2.0(5H,m),2.0-2.6(4H,m),3.17
(1H,m),3.6-4.5(15H,m),4.63-5.33(13H,m),
5.53(1H,d,J=5.9Hz),6.73(1H,d,J=8.2Hz),
6.82(1H,d,J=8.2Hz),6.84(1H,s),6.95-7.52
(7H,m),7.66(1H,d,J=7.6Hz),7.7-7.9(3H,m),
8.05(1H,d,J=9.1Hz),8.15(1H,d,J=7.6Hz),
8.85(1H,s)
FAB-MASS:m/z=1279(M++Na)
元素分析 理论值C54H73N8O23SNa·5H2O:
C48.14,H6.21,N8.32
实验值:C48.43,H6.28,N8.30
实施例9
IR(KBr):3347,2956,1664,1633,1508,1444,1268,
1047cm-1
NMR(DMSO-d6,δ):0.9-1.1(9H,m),1.06(3H,d,
J=5.9Hz),1.3-1.5(8H,m),1.6-2.0(7H,m),2.1-
2.4(3H,m),2.5-2.6(1H,m),3.1-3.3(1H,m),
3.6-4.4(17H,m),4.7-5.0(8H,m),5.09(1H,d,
J=5.5Hz),5.16(1H,d,J=3.1Hz),5.24(1H,d,
J=4.5Hz),6.73(1H,d,J=8.2Hz),6.8-6.9(2H,
m),6.98(1H,d,J=8.3Hz),7.05(1H,d,
J=1.7Hz),7.3-7.6(5H,m),8.08(1H,d,
J=8.9Hz),8.25(1H,d,J=8.4Hz),8.54(1H,d,
J=7.5Hz),8.83(1H,s)
FAB-MASS:m/z=1257(M++Na)
元素分析 理论值C52H75N8O23SNa·4H2O:
C47.78,H6.40,N8.57
实验值:C47.88,H6.71,N8.53
实施例10
IR(KBr):3350,2931,1664,1625,1529,1440,1276,
1226,1047cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.8Hz),0.97(3H,
d,J=6.7Hz),1.12(3H,d,J=5.9Hz),1.2-1.5
(10H,m),1.6-2.1(5H,m),2.1-2.4(4H,m),3.1-
3.3(1H,m),3.5-4.6(15H,m),4.7-5.0(3H,m),
5.0-5.2(7H,m),5.27(1H,d,J=4.4Hz),5.55
(1H,d,J=5.7Hz),6.73(1H,d,J=8.2Hz),6.8-7.0
(2H,m),7.0-7.2(4H,m),7.3-7.6(2H,m),7.90
(1H,d,J=8.8Hz),8.0-8.2(2H,m),8.8-8.9(2H,
m),9.06(1H,d,J=7.2Hz)
FAB-MASS:m/z=1281(M++Na)
元素分析 理论值C53H71N8O24SNa·5H2O:
C47.18,H6.05,N8.30
实验值:C46.97,H6.27,N8.22
实施例11
NMR(DMSO-d6,δ):0.87-1.05(6H,m),1.10(3H,d,
J=5.7Hz),1.3-1.5(4H,m),1.6-1.9(5H,m),2.2-
2.5(3H,m),2.6(1H,m),3.1-3.2(1H,m),3.7-
4.5(15H,m),4.8-5.1(8H,m),5.09(1H,d,
J=5.64Hz),5.16(1H,d,J=3.2Hz),5.26(1H,d,
J=4.2Hz),5.52(1H,d,J=6.0Hz),6.73(2H,d,
J=8.4Hz),6.8-6.9(2H,m),7.0-7.1(3H,m),7.2-
7.4(4H,m),7.6-7.8(6H,m),8.11(1H,d,
J=8.4Hz),8.29(1H,d,J=8.4Hz),8.51(1H,d,
J=7.7Hz),8.85(1H,s)
FAB-MASS:m/z=1273(M++Na)
元素分析 理论值C55H71N8O22SNa·4H2O:
C49.92,H6.02,N8.47
实验值:C49.79,H6.14,N8.45
实施例12
IR(KBr):3330,2929,1670,1629,1533,1440,1280,
1226,1045,804cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.7Hz),0.97(3H,
d,J=6.7Hz),1.08(3H,d,J=5.9Hz),1.2-1.6
(10H,m),1.6-2.0(5H,m),2.1-2.5(4H,m),3.1-
3.3(1H,m),3.6-4.5(15H,m),4.8-5.1(9H,m),
5.17(1H,d,J=3.0Hz),5.25(1H,d,J=4.5Hz),
5.56(1H,d,J=5.6Hz),6.73(1H,d,J=8.2Hz),
6.83(1H,d,J=6.8Hz),7.1-7.2(3H,m),7.3-7.5
(3H,m),7.85(1H,d,J=8.8Hz),8.0-8.2(3H,m),
8.84(1H,s),8.96(1H,d,J=7.2Hz)
FAB-MASS:m/z=1269(M++Na)
元素分析 理论值C52H71N8O22S2Na·4H2O:
C47.34,H6.04,N8.49
实验值:C47.21,H5.96,N8.41
实施例13
IR(KBr):3345,2927,1664,1629,1515,1442,
1274,1047cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.7Hz),0.97(3H,
d,J=6.7Hz),1.10(3H,d,J=5.9Hz),1.2-1.4
(10H,m),1.5-2.5(8H,m),2.46(3H,s),2.69
(2H,t,J=7.7Hz),3.1-3.4(2H,m),3.6-4.5(17H,
m),4.8-5.2(8H,m),6.7-7.0(3H,m),7.05(1H,
d,J=1.7Hz),7.14(1H,s),7.3-7.6(5H,m),8.0-
8.2(2H,m),8.47(1H,d,J=7.0Hz),8.84(1H,s)
FAB-MASS:m/z=1251(M++Na)
元素分析 理论值C53H73N8O22SNa·3H2O:
C49.61,H6.21,N8.73
实验值:C49.88,H6.44,N8.74
实施例14
IR(KBr):3340,1672,1627,1542,1513,1440,1268,
1045cm-1
NMR(DMSO-d6,δ):0.84(3H,t,J=6.7Hz),0.94(3H,
d,J=6.7Hz),1.07(3H,d,J=6.0Hz),1.2-1.4
(12H,m),1.6-2.0(5H,m),2.1-2.4(3H,m),2.6
(1H,m),2.96(2H,t,J=7.4Hz),3.1-3.3(1H,m),
3.6-4.5(13H,m),4.7-5.2(11H,m),5.50(1H,d,
J=5.7Hz),6.73(1H,d,J=8.2Hz),6.8-6.9(2H,
m),7.04(1H,s),7.2-7.5(3H,m),7.72(1H,d,
J=8.5Hz),7.91(1H,d,J=8.4Hz),8.05(1H,d,
J=8.4Hz),8.2-8.4(1H,m),8.80(1H,d,
J=7.7Hz),8.83(1H,s)
FAB-MASS:m/z=1252(M++Na)
元素分析 理论值C52H72N9O22SNa·6H2O:
C46.67,H6.33,N9.42
实验值:C46.72,H6.53,N9.45
实施例15
IR(KBr):3350,2935,1664,1627,1517,1446,1251,
1045cm-1
NMR(DMSO-d6,δ):0.90-1.1(6H,m),1.10(3H,d,
J=5.9Hz),1.2-1.4(6H,m),1.6-2.4(8H,m),2.6-
2.7(1H,m),3.1-3.3(1H,m),3.7-4.5(16H,m),
4.7-5.4(11H,m),5.51(1H,d,J=5.6Hz),6.7-7.0
(3H,m),7.0-7.6(7H,m),7.74(1H,d,J=8.6Hz),
8.0-8.4(5H,m),8.7-8.8(1H,m),8.84(1H,s)
FAB-MASS:m/z=1301(M++Na)
元素分析 理论值C55H71N10O22SNa·6H2O:
C47.62,H6.03,N10.01
实验值:C47.65,H6.03,N10.03
实施例16
IR(Nujol):3353,1668,1627,1540,1515,1500cm-1
NMR(DMSO-d6,δ):0.80-1.00(6H,m),1.06(3H,d,
J=5.9Hz),1.20-1.53(4H,m),1.60-1.95(5H,m),
2.00-2.65(8H,m),2.80(2H,t,J=7.5Hz),3.05-
3.45(1H,m),3.50-3.85(2H,m),3.90-4.48(11H,
m),4.65-5.38(11H,m),5.47(1H,d,J=6.0Hz),
6.65-6.90(2H,m),6.90-7.10(2H,m),7.10-7.65
(11H,m),7.90-8.25(2H,m),8.30(1H,d,
J=7.8Hz),8.84(1H,s)
FAB-MASS:m/z=1275.3(M++Na)
元素分析 理论值C55H73N8O22SNa·3H2O:
C50.53,H6.09,N8.57
实验值:C50.48,H6.39,N8.57
实施例17
IR(Nujol):3351,1656,1623,1538,1515cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.7Hz),0.96(3H,
d,J=6.7Hz),1.08(3H,d,J=5.8Hz),1.15-1.40
(8H,m),1.50-2.00(5H,m),2.10-2.48(4H,m),
2.52-2.70(2H,m),3.05-3.28(1H,m),3.60-4.50
(13H,m),4.70-5.20(9H,m),5.25(1H,d,
J=4.6Hz),5.52(1H,d,J=6.0Hz),6.68-6.92 (4H,
m),7.04(1H,d,J=1.0Hz),7.22-7.50(5H,m),
7.55-7.82(7H,m),8.14(1H,d,J=8.4Hz),8.31
(1H,d,J=8.4Hz),8.54(1H,d,J=7.7Hz),8.84
(1H,s)
FAB-MASS:m/z=1285(M++Na)
实施例18
IR(Nujol):3351,1668,1627,1540,1515cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.8Hz),0.96(3H,
d,J=6.7Hz),1.06(3H,d,J=5.8Hz),1.17-1.48
(4H,m),1.50-1.95(5H,m),2.05-2.70(8H,m),
2.70-2.95(2H,m),3.05-3.30(1H,m),3.60-3.90
(2H,m),3.90-4.50(11H,m),4.65-5.10(9H,m),
5.15(1H,d,J=3.2Hz),5.23(1H,d,J=4.2Hz),
5.48(1H,d,J=6.0Hz),6.67-6.90(3H,m),7.03
(1H,d,J=1.5Hz),7.15-7.80(11H,m),8.00-8.20
(2H,m),8.29(1H,d,J=7.8Hz),8.84(1H,s)
FAB-MASS:m/z=1259(M++Na)
元素分析 理论值C55H73N8O21SNa·6H2O:
C50.30,H6.52,N8.53
实验值:C50.42,H6.50,N8.45
实施例19
IR(Nujol):3351,1668,1652,1623,1540cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.7Hz),0.96(3H,
d,J=6.7Hz),1.07(3H,d,J=6.0Hz),1.25-1.45
(4H,m),1.50-2.00(5H,m),2.05-2.48(4H,m),
2.50-2.75(2H,m),3.60-4.50(13H,m),4.68-5.25
(10H,m),5.27(1H,d,J=4.5Hz),5.53(1H,d,
J=6.0Hz),6.67-6.98(4H,m),7.05(1H,d,
J=1.0Hz),7.22-7.58(5H,m),7.58-7.90(7H,m),
8.16(1H,d,J=9.0Hz),8.34(1H,d,J=8.4Hz),
8.57(1H,d,J=7.7Hz),8.85(1H,s)
FAB-MASS:m/z=1258(M++Na)
元素分析 理论值C55H71N8O21SNa·5H2O:
C49.84,H6.15,N8.45
实验值:C49.77,H6.27,N8.39
实施例20
IR(Nujol):3353,1670,1629,1540,1508cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.5Hz),0.97(3H,
d,J=6.8Hz),1.04(3H,d,J=5.9Hz),1.20-1.58
(8H,m),1.60-1.96(5H,m),2.08-2.60(6H,m),
2.70-3.00(2H,m),3.00-3.40(1H,m),3.60-3.85
(2H,m),3.85-4.50(13H,m),4.50-5.60(12H,m),
6.65-6.90(3H,m),7.00-7.15(3H,m),7.18-7.50
(4H,m),7.59(1H,s),7.62-7.78(2H,m),7.95-
8.20(2H,m),8.30(1H,d,J=7.7Hz),8.83(1H,
s)
FAB-MASS:m/z=1277(M++Na)
元素分析 理论值C55H75N8O22SNa·4H2O:
C49.77,H6.30,N8.44
实验值:C49.67,H6.31,N8.40
实施例21
IR(Nujol):3351,1654,1623,1538,1515cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.7Hz),0.97(3H,
d,J=6.7Hz),1.08(3H,d,J=5.9Hz),1.20-1.58
(8H,m),1.66-1.95(5H,m),2.10-2.60(4H,m),
3.09-3.30(1H,m),3.58-4.60(15H,m),4.69-5.20
(10H,m),5.24(1H,d,J=4.5Hz),5.51(1H,d,
J=6.0Hz),6.68-6.95(4H,m),7.04(1H,d,
J=1.0Hz),7.10-7.73(7H,m),7.73-7.90(2H,m),
7.98(1H,d,J=1.9Hz),8.10(1H,d,J=8.4Hz),
8.32(1H,d,J=8.4Hz),8.50(1H,d,J=7.7Hz),
8.84(1H,s)
FAB-MASS:m/z=1275(M++Na)
元素分析 理论值C55H73N8022SNa·5H20:
C50.38,H6.38,N8.55
实验值:C49.98,H6.37,N8.41
实施例22
IR(KBr):3340,2931,1664,1627,1531,1444,1278,
1047cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.6Hz),0.96(3H,
d,J=6.8Hz),1.08(3H,d,J=5.9Hz),1.2-1.4(6H,
m),1.5-1.7(2H,m),1.7-2.1(3H,m),2.2-2.4
(3H,m),2.6-2.7(3H,m),3.1-3.2(1H,m),3.7-
4.6(13H,m),4.78(1H,d,J=6.0Hz),4.8-5.1
(1H,m),5.09(1H,d,J=5.6Hz),5.16(1H,d,
J=3.2Hz),5.24(1H,d,J=4.4Hz),5.52(1H,d,
J=6.0Hz),6.73(1H,d,J=8.2Hz),6.83(2H,d,
J=8.3Hz),7.05(1H,s),7.3-7.5(5H,m),7.65
(2H,d,J=8.2Hz),7.74(2H,d,J=8.4Hz),7.98
(2H,d,J=8.4Hz),8.11(1H,d,J=8.4Hz),8.31
(1H,d,J=8.4Hz),8.79(1H,d,J=7.7Hz),8.84
(1H,s)
FAB-MASS:m/z=1245(M++Na)
元素分析 理论值C54H71N8O21SNa·4H2O:
C50.07,H6.15,N8.65
实验值:C50.26,H6.44,N8.67
实施例23
NMR(DMSO-d6,δ):0.91(3H,t,J=6.7Hz),0.96(3H,
d,J=6.8Hz),1.05(3H,d,J=5.6Hz),1.2-1.5(6H,
m),1.6-2.1(5H,m),2.1-2.7(4H,m),3.0-3.5
(9H,m),3.6-4.5(15H,m),4.6-5.6(11H,m),
6.73(1H,d,J=8.2Hz),6.8-6.9(4H,m),6.95
(2H,d,J=8.6Hz),7.02(2H,d,J=9.2Hz),7.04
(1H,s),7.2-7.5(3H,m),7.82(2H,d,J=8.6Hz),
8.06(1H,d,J=8Hz),8.25(1H,d,J=6.7Hz),8.43
(1H,d,J=6.7Hz),8.85(1H,s)
IR(KBr):3350,1668,1629,1510cm-1
FAB-MASS:m/z=1345(M+Na)
元素分析 理论值C58H79N10O22SNa·6H2O:
C48.67,H6.41,N9.78
实验值:C48.80,H6.46,N9.82
实施例24
主产物
IR(KBr):3350,1668,1631,1047cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.7Hz),1.08(3H,
d,J=5.7Hz),1.2-1.6(10H,m),1.6-2.4(8H,m),
2.5-2.7(1H,m),3.18(1H,m),3.21(3H,s),
3.29(2H,t,J=6.4Hz),3.6-3.83(2H,m),3.83-
4.6(13H,m),4.7-5.4(11H,m),5.51(1H,d,
J=5.9Hz),6.73(1H,d,J=8.2Hz),6.83(1H,d,
J=8.2Hz),6.85(1H,s),7.04(2H,d,J=8.4Hz),
7.06(1H,s),7.31(1H,s),7.2-7.5(2H,m),
7.67(2H,d,J=8.4Hz),7.71(2H,d,J=8.4Hz),
7.96(2H,d,J=8.4Hz),8.06(1H,d,J=8Hz),8.25
(1H,d,J=6.7Hz),8.74(1H,d,J=6.7Hz),8.84
(1H,s)
FAB-MASS:m/z=1319(M+Na)
元素分析 理论值C57H77N8O23SNa·4H2O:
C49.99,H6.26,N8.18
实验值:C49.74,H6.27,N8.06
次产物
IR(KBr):3350,1668,1631cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.7Hz),1.08(3H,
d,J=5.7Hz),1.2-1.6(6H,m),1.6-2.1(7H,m),
2.1-2.5(3H,m),2.5-2.7(1H,m),3.18(1H,m),
3.6-3.8(2H,m),3.8-4.6(13H,m),4.6-5.2(12H,
m),5.26(1H,d,J=4.6Hz),5.53(1H,d,
J=5.8Hz),5.6-6.0(1H,m),6.73(1H,d,
J=8.2Hz),6.83(1H,d,J=8.3Hz),6.85(1H,s),
7.04(2H,d,J=8.5Hz),7.06(1H,s),7.30(1H,
s),7.2-7.5(2H,m),7.68(2H,d,J=8.5Hz),7.72
(2H,d,J=8.5Hz),7.96(2H,d,J=8.5Hz),8.06
(1H,d,J=8Hz),8.25(1H,d,J=6.7Hz),8.74(1H,
d,J=6.7Hz),8.85(1H,s)
FAB-MASS:m/z=1287(M+Na)
元素分析 理论值C56H73N8NaO22S·7H2O:
C48.34,H6.30,N8.05
实验值:C48.19,H6.19,N7.99
实施例25
IR(KBr):3350,2935,2873,1668,1629,1538,1506,
1438,1257,1049cm-1
NMR(DMSO-d6,δ):0.9-1.0(6H,m),1.08(3H,d,
J=5.7Hz),1.2-1.6(4H,m),1.6-2.0(5H,m),2.1-
2.4(3H,m),2.5-2.6(1H,m),3.1-3.2(1H,m),
3.6-4.6(15H,m),4.7-5.2(10H,m),5.26(1H,d
J=4.5Hz),5.55(1H,d,J=5.9Hz),6.7-6.9(3H,
m),7.0-7.6(7H,m),7.85(2H,d,J=8.6Hz),7.9-
8.2(4H,m),8.26(1H,d,J=7.7Hz),8.8-9.0(2H,
m)
FAB-MASS:m/z=1314.3(M+Na)+
元素分析 理论值C56H70N9O23NaS·7H2O:
C47.42,H5.97,N8.89
实验值:C47.33,H5.85,N8.73
实施例26
向起始化合物(1g)和丁二酰亚氨基4-(4-辛氧基苯基)哌嗪-1-羧酸酯(0.45g)在N,N-二甲基甲酰胺(10ml)中的溶液里加入4-二甲基氨基吡啶(0.141g),在50℃搅拌5天。将反应混合物与乙酸乙酯一起研磨。过滤收集沉淀物,减压干燥。将粉末溶在水中,在离子交换树脂(DOWEX-50WX4)上进行柱色谱,用水洗脱。将含有目标化合物的级分合并,在ODS(YMC-凝胶ODS-AM·S-50)上进行柱色谱,用50%乙腈水溶液洗脱。将含有目标化合物的级分合并,减压蒸发去掉乙腈。将残余物冷冻干燥,得到粗制的目标化合物(23)。将目标化合物(23)的粗品粉末用制备型HPLC纯化,使用C18μBondapak树脂(Waters Associates公司),用由乙腈-pH3磷酸盐缓冲液=40∶60构成的溶剂体系洗脱,使用岛津LC-8A泵,流速为80ml/分。用设定在240μm的紫外检测器监测柱子。将含有目标化合物的各级分合并,减压蒸发去除乙腈。残余物在离子交换树脂(DOWEX-50WX4)上进行柱色谱,用水洗脱。将含有目标化合物的级分合并,在ODS(YMC-凝胶ODS-AM·S-50)上进行柱色谱,用50%的乙腈水溶液洗脱。将含有目标化合物的级分合并,减压蒸发去掉乙腈。将残余物冷冻干燥,得到目标化合物(23)(60mg)。
IR(KBr):3347,1629,1511,1245cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.7Hz),0.95(3H,
d,J=6.8Hz),1.06(3H,d,J=5.9Hz),1.2-1.5
(10H,m),1.55-1.92(5H,m),2.0-2.65(4H,m),
2.8-3.05(5H,m),3.2-4.47(17H,m),4.6-5.6
(12H,m),6.6-7.0(7H,m),7.03(1H,s),7.2-7.5
(3H,m),7.9-8.3(3H,m),8.84(1H,s)
FAB-MASS:m/z=1297(M++Na)
元素分析 理论值C54H79N10O22SNa·6H2O·CH3CN:
C47.22,H6.65,N10.82
实验值:C47.58,H7.05,N10.85
实施例27
向1-羟基苯并三唑(0.53g)和2-(4-辛氧苯氧基)乙酸(1g)在二氯甲烷(30ml)中的悬浮液里加入1-乙基-3-(3’-二甲氨基丙基)碳化二亚胺盐酸盐(WSCD·HCl)(0.886g),在环境温度下搅拌3小时。将反应混合物加到水中。分出有机层,用硫酸镁干燥。滤除硫酸镁,将滤液减压蒸发,得到1-〔2-(4-辛氧苯氧基)乙酰基〕苯并三唑3-氧化物(892mg)。向起始化合物(1.79g)和1-〔2-(4-辛氧苯氧基)乙酰〕苯并三唑3-氧化物(892mg)在N,N-二甲基甲酰胺(18ml)中的溶液里加入4-(N,N-二甲氨基)吡啶(0.297g),在环境温度下搅拌12小时。将反应混合物与乙酸乙酯一起研磨。过滤收集沉淀,减压干燥。将粉末加到水中,在DOWEX-50WX4上进行离子交换柱色谱,用水洗脱。将含有目标化合物的级分合并,在ODS(YMC-凝胶ODS-AM·S-50)上进行柱色谱,用50%甲醇水溶液洗脱。将含有目标化合物的级分合并,减压蒸发去除甲醇。残余物冷冻干燥,得到目标化合物(24)(1.75g)。
IR(KBr):3350,1666,1629,1228cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.9Hz),0.95(3H,
d,J=6.7Hz),1.04(3H,d,J=5.7Hz),1.15-1.5
(10H,m),1.55-2.0(5H,m),2.05-2.5(4H,m),
3.16(1H,m),3.72(2H,m),3.88(3H,t,
J=6.3Hz),4.41(2H,s),3.93-4.6(11H,m),
4.69-5.25(10H,m),5.28(1H,d,J=4.3Hz),5.57
(1H,d,J=5.7Hz),6.73(1H,d,J=8.2Hz),6.8-7.0
(5H,m),7.04(1H,s),7.09(1H,s),7.3-7.4
(2H,m),7.92-8.17(2H,m),8.29(1H,d,
J=7.5Hz),8.84(1H,s)
FAB-MASS:m/z=1243(M++Na)
元素分析 理论值C51H73N8O23SNa·4H2O:
C47.36,H6.31,N8.66
实验值:C47.22,H6.44,N8.37
目标化合物(28)至(31)按照与实施例27相似的方式得到。
实施例28
IR(KBr):3350,2933,1664,1628,1446,1205,
1045cm-1
NMR(DMSO-d6,δ):0.8-1.1(9H,m),1.2-2.0(19H,m),
2.1-2.3(3H,m),3.6-3.8(4H,m),3.9-4.4(13H,m),
4.6-5.0(8H,m),5.07(1H,d,J=5.6Hz),5.14(1H,
d,J=3.2Hz),5.23(1H,d,J=4.3Hz), 5.46(1H,d,
J=6.7Hz),6.7-6.9(3H,m),7.04(1H,s),7.2-7.5
(6H,m),7.8-8.0(3H,m),8.05(1H,d,J=8.4Hz),
8.2-8.4(2H,m),8.83(1H,s)
FAB-MASS:m/z=1360(M++Na)
元素分析 理论值C59H80N9O23SNa·6H2O:
C48.99,H6.41,N8.72
实验值:C48.92,H6.37,N8.64
实施例29
IR(KBr):3350,2927,1668,1627,1535,1515,1452,
1440,1286,1045cm-1
NMR(DMSO-d6,δ):0.83(3H,t,J=6.7Hz),0.95(3H,
d,J=6.7Hz),1.07(3H,d,J=5.9Hz),1.2-1.4
(12H,m),1.6-2.0(5H,m),2.1-2.4(3H,m),2.6
(1H,m),2.82(2H,t,J=7.4Hz),3.1-3.2(1H,m),
3.6-4.5(13H,m),4.7-5.2(11H,m),5.4-5.6(1H,
m),6.72(1H,d,J=8.2Hz),6.82(2H,d,
J=8.1Hz),7.03(1H,s),7.2-7.4(3H,m),7.47
(1H,d,J=8.5Hz),7.69(1H,d,J=8.5Hz),8.1-8.2
(2H,m),8.23(1H,d,J=8.4Hz),8.62(1H,d,
J=7.8Hz),8.83(1H,s)
FAB-MASS:m/z=1251(M++Na)
元素分析 理论值C52H73N10O21SNa·5H2O:
C47.34,H6.34,N10.61
实验值:C47.30,H6.4 5,N10.45
实施例30
NMR(DMSO-d6,δ):0.86(3H,t,J=6.8Hz),0.96(3H,
t,J=6.7Hz),1.05(3H,t,J=5.8Hz),1.2-1.5
(10H,m),1.6-2.0(5H,m),2.2-2.4(3H,m),2.5-
2.6(1H,m),3.1-3.2(1H,m),3.7-4.5(15H,m),
4.7-5.0(8H,m),5.10(1H,d,J=5.6Hz),5.17
(1H,d,J=3.1Hz),5.26(1H,d,J=4.5Hz),5.52
(1H,d,J=5.8Hz)6.73(1H,d,J=8.2Hz),6.8-7.0
(3H,m),7.04(1H,s),7.2-7.4(3H,m),8.0-8.3
(3H,m),8.68(1H,d,J=2.3Hz),8.7-8.8(1H,m),
8.85(1H,m)
FAB-MASS:m/z=1214(M++Na)
元素分析 理论值C49H70N9O22SNa·4H2O:
C46.55,H6.22,N9.97
实验值:C46.29,H6.18,N9.71
实施例31
IR(Nujol):3342,2210,1668,1623cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.7Hz),0.97(3H,
d,J=6.7Hz),1.08(3H,d,J=6.7Hz),1.20-1.60
(8H,m),1.60-2.00(5H,m),2.05-2.50(4H,m),
3.05-3.30(1H,m),3.60-4.60(15H,m),4.65-5.18
(10H,m),5.24(1H,d,J=4.5Mz),5.58(1M,d,
J=6.0Hz),6.68-7.10(4H,m),7.15-7.65(5H,m),
7.80-8.30(6H,m),8.84(1H,s),9.18(1H,d,
J=7.7Hz)
FAB-MASS:m/z=1273.5(M++Na)
实施例32
向6-庚氧基-2-萘甲酸(0.358g)和三乙胺(0.174ml)在N,N-二甲基甲酰胺(10ml)中的溶液里加入二苯基磷酰叠氮化物(0.4ml),在环境温度下搅拌1小时.然后将反应混合物在100℃搅拌1小时。冷却后,向反应混合物中加入起始化合物(1g)和4-(N,N-二甲氨基)吡啶(0.140g),在环境温度下搅拌10小时。将反应混合物与乙酸乙酯一起研磨。过滤收集沉淀,减压干燥。将粉末溶在水中,在离子交换树脂(DOWEX-50WX4)上进行柱色谱,用水洗脱。将含有目标化合物的级分合并,在ODS(YMC-凝胶·ODS-AM·S-50)上进行柱色谱,用50%的乙腈水溶液洗脱。将含有目标化合物的级分合并,减压蒸发除去乙腈。将残余物冷冻干燥,得到目标化合物(29)(0.832g)。
IR(KBr):3350,1664,1629,1546,1240cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.6Hz),0.97(3H,
d,J=6.7Hz),1.08(3H,d,J=5.9Hz),1.2-1.55
(8H,m),1.55-2.0(5H,m),2.1-2.5(4H,m),
3.18(1H,m),3.6-3.8(3H,m),3.9-4.5(13H,m),
4.7-4.95(3H,m),5.0-5.3(7H,m),5.59(1H,d,
J=5.8Hz),6.52(1H,d,J=8.1Hz),6.73(1H,d,
J=8.2Hz),6.83(1H,d,J=8.2Hz),6.90(1H,s),
7.0-7.15(3H,m),7.20(1H,s),7.27-7.4(3H,
m),7.6-7.7(2H,m),7.87(1H,s),7.95-8.2(2H,
m),8.69(1H,s),8.85(1H,s)
FAB-MS:m/z=1264(M++Na)
元素分析 理论值C53H72N9O22SNa·5H2O:
C47.78,H6.20,N9.46
实验值:C47.65,H6.42,N9.34
目标化合物(33)按照与实施例32相似的方式得到。
实施例33
IR(KBr):3350,1666,1629,1537,1240cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.7Hz),0.97(3H,
d,J=6.7Hz),1.09(3H,d,J=5.8Hz),1.2-1.55
(8H,m),1.55-2.0(5H,m),2.07-2.6(4H,m),
3.18(1H,m),3.6-3.85(3H,m),3.9-4.5(13H,
m),4.7-4.98(3H,m),5.0-5.3(7H,m),5.57(1H,
d,J=5.9Hz),6.50(1H,d,J=8.1Hz),6.73(1H,d,
J=8.2Hz),6.82(1H,dd,J=8.2and1.7Hz),6.87
(1H,s),6.97(2H,d,J=8.8Hz),7.05(1H,d,
J=1.7Hz),7.10(1H,s),7.23-7.43(2H,m),7.38
(2H,d,J=8.8Hz),7.50(2H,d,J=8.8Hz),7.52
(2H,d,J=8.8Hz),8.0-8.15(2H,m),8.65(1H,
s),8.84(1H,s)
FAB-MASS:m/z=1290(M++Na)
元素分析 理论值C55H74N9O22SNa·7H2O:
C47.38,H6.36,N9.04
实验值:C47.67,H6.53,N9.03
实施例34
将起始化合物(2.45g)、3-〔4-(4-戊基苯基)苯基〕丙炔酸(0.90g)、1-乙基-3-(3’-二甲氨基丙基)碳化二亚胺盐酸盐(WSCD-HCl)(0.59g)和三乙胺(0.43ml)在N,N-二甲基甲酰胺(50ml)中的溶液在环境温度下搅拌15小时。将反应混合物用乙酸乙酯稀释,过滤收集所形成的沉淀,依次用乙酸乙酯和异丙醚洗,减压干燥。将粉末溶在水中,在离子交换树脂上(DOWEX-50WX4,钠型,50ml)进行柱色谱,用水洗脱。将含有目标化合物的级分合并,在ODS(YMC-凝胶·ODS-AM·S-50,50ml)上进行反相色谱分离,用(水∶乙腈=10∶0-7∶3,v/v)洗脱。将含有目标化合物的级分合并,减压蒸发去除乙腈。残余物冷冻干燥,得到目标化合物(31)(1.53g)。
IR(Nujol):3351,2212,1668,1627cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.5Hz),0.96(3H,
d,J=6.7Hz),1.08(3H,d,J=5.8Hz),1.20-1.50
(4H,m),1.50-2.00(5H,m),2.03-2.55(4H,m),
2.62(2H,t,J=7.5Hz),3.17(1H,t,J=8.4Hz),
3.55-4.57(15H,m),4.65-5.13(9H,m),5.16(1H,
d,J=3.2Hz),5.24(1H,d,J=4.5Hz),5.58(1H,d,
J=5.8Hz),6.67-6.90(3H,m),6.93-7.10(2H,m),
7.15-7.50(4H,m),7.50-7.90(6H,m),8.06(1H,
d,J=8.4Hz),8.15(1H,d,J=7.7Hz),8.84(1H,
s),9.19(1H,d,J=7.1Hz)
FAB-NASS:m/z=1255(M++Na)
元素分析 理论值C55H69N8O21SNa·4H2O:
C50.61,H5.95,N8.58
实验值:C50.47,H6.00,N8.54
实施例35
向1-羟基苯并三唑(501mg)和4-(4-庚基苯基)苯甲酸(1g)在二氯甲烷(30ml)中的悬浮液里加入1-乙基-3-(3,-二甲氨基丙基)碳化二亚胺盐酸盐(WSCD·HCl)(839mg),在环境温度下搅拌3小时。将反应混合物加到水中。分离出有机层,用硫酸镁干燥。滤除硫酸镁,将滤液减压蒸发,得到1-〔4-(4-庚基苯基)苯甲酰〕苯并三唑3-氧化物。向起始化合物(2.49g)和1-〔4-(4-庚基苯基)苯甲酰〕苯并三唑3-氧化物在N,N-二甲基甲酰胺(25ml)中的溶液里加入4-(N,N-二甲氨基)吡啶(381mg),在环境温度下搅拌12小时。将反应混合物与乙酸乙酯一起研磨。过滤收集沉淀物,减压干燥。将残余物溶在水中,在离子交换树脂(DOWEX-50WX4)上进行柱色谱。将含有目标化合物的级分合并,在ODS(YMC-凝胶·ODS-AM·S-50)上进行柱色谱,用30%的乙腈水溶液洗脱。将含有目标化合物的级分合并,减压蒸发除去乙腈。残余物冷冻干燥后得到目标化合物(32)(1.99g)。
IR(Nujol):3350,2852,1749,1621,1457,1376,
1045cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.7Hz),0.96(3H,
d,J=6.7Hz),1.08(3H,d,J=5.9Hz),1.5-1.7(2H,
m),1.7-2.2(3H,m),2.2-2.5(3H,m),2.6-2.8
(3H,m),3.1-3.2(1H,m),3.7-4.6(13H,m),
4.7-5.2(8H,m),5.12(1H,d,J=5.5Hz),5.18
(1H,d,J=2.9Hz),5.27(1H,d,J=4.4Hz),5.54
(1H,d,J=5.8Hz),6.7-6.9(3H,m),7.05(1H,s),
7.2-7.4(5H,m),7.65(2H,d,J=8.0Hz),7.74
(2H,d,J=8.3Hz),7.98(2H,d,J=8.3Hz),8.11
(1H,d,J=8.7Hz),8.28(1H,d,J=8.4Hz),8.78
(1H,d,J=7.3Hz),8.85(1H,s)
FAB-MASS:m/z=1259(M++Na)
元素分析 理论值C55H73N8O21SNa·5H2O:
C49.77,H6.30,N8.44
实验值:C49.98,H6.44,N8.41
目标化合物(36)至(107)按照与实施例1相似的方式得到。
实施例36
IR(KBr):3350,1675.8,1629.6,1515.8cm-1
NMR(DMSO-d6,δ):0.86(6H,d,J=6.6Hz),0.96(3H,d,
J=6.6Hz),1.06(3H,d,J=5.7Hz),1.1-1.3(2H,m),
1.4-2.0(6H,m),2.0-2.7(4H,m),3.1-3.5(9H,m),
3.66(2H,t,J=7.3Hz),3.6-4.5(13H,m),4.7-5.6
(12H,m),6.73(1H,d,J=8.3Hz),6.82(1H,d,
J=8.3Hz),6.8-6.9(1H,m),7.02(2H,d,J=9.0Hz),
7.04(1H,s),7.11(2H,d,J=9.0Hz),7.2-7.6(3H,
m),7.50(2H,d,J=9.0Hz),7.82(2H,d,J=9.0Hz),
8.1(1H,d,J=8.5Hz),8.28(1H,d,J=8.5Hz),8.33
(1H,s),8.45(1H,d,J=7.0Hz),8.84(1H,s)
FAB-MASS:m/z=1412(M+Na)
元素分析 理论值C60H80N13O22SNa·9H2O:
C46.42,H6.36,N11.73
实验值:C46.64,H6.43,N11.62
实施例37
IR(KBr):3350,1668.1,1629.6,1268.9cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.6Hz),0.96(3H,d,
J=6.7Hz),1.07(3H,d,J=5.9Hz),1.2-1.4(10H,m),
1.4-2.0(5H,m),2.0-2.5(4H,m),2.61(2H,t,
J=7.2Hz),3.1-3.3(1H,m),3.6-4.5(13H,m),4.40
(2H,s),4.6-5.3(11H,m),5.60(1H,d,J=5.8Hz),
6.73(1H,d,J=8.2Hz),6.82(1H,d,J=8.2Hz),6.6-
6.9(1H,m),7.04(1H,s),7.0-7.1(1H,m),7.32
(2H,d,J=8.5Hz),7.2-7.5(2H,m),7.58(2H,d,
J=8.5Hz),7.93(1H,d,J=7Hz),8.04(1H,d,
J=9.4Hz),8.41(1H,s),8.44(1H,d,J=9.4Hz),8.84
(1H,s)
FAB-MASS:m/z=1294(M+Na)
元素分析 理论值C53H74N11O22SNa·7H2O:
C45.52,H6.34,N11.02
实验值:C45.47,H6.27,N10.93
实施例38
主产物
IR(KBr):3349.7,1670.1,1627.6,1508.1cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.6Hz),1.06(3H,d,
J=5.7Hz),1.2-1.6(8H,m),1.6-2.1(5H,m),2.1-2.7
(4H,m),3.0-3.2(5H,m),3.21(3H,s),3.30(2H,
t,J=6.5Hz),3.3-3.5(4H,m),3.6-4.5(15H,m),
4.7-5.3(11H,m),5.49(1H,d,J=5.9Hz),6.73(1H,
d,J=8.3Hz),6.8-6.9(4H,m),6.95(2H,d,
J=9.2Hz),7.01(2H,d,J=8.5Hz),7.04(1H,s),7.20
(1H,s),7.2-7.5(2H,m),7.81(2H,d,J=8.5Hz),
8.09(1H,d,J=8.7Hz),8.28(1H,d,J=8.7Hz),8.45
(1H,d,J=6.7Hz),8.84(1H,s)
FAB-MASS:m/z=1389(M+Na)
元素分析 理论值C60H83N10O23SNa·8H2O:.
C47.68,H6.60,N9.27
实验值:C47.83,H6.72,N9.27
次产物
IR(KBr):3338.2,1646.9,1511.9cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.7Hz),1.06(3H,d,
J=5.7Hz),1.3-1.6(4H,m),1.6-2.7(11H,m),3.0-
3.2(5H,m),3.3-3.5(4H,m),3.6-4.5(15H,m),
4.7-5.3(13H,m),5.48(1H,d,J=5.9Hz),5.7-6.0
(1H,m),6.73(1H,d,J=8.2Hz),6.8-6.9(4H,m),
6.94(2H,d,J=9.3Hz),7.01(2H,d,J=8.6Hz),7.04
(1H,s),7.2-7.5 (3H,m),7.81(2H,d,J=8.6Hz),
8.06(1H,d,J=8.7Hz),8.25(1H,d,J=8.7Hz),8.42
(1H,d,J=6.7Hz),8.84(1H,s)
FAB-MASS:m/z=1357(M+Na)
元素分析 理论值C59H79N10O22SNa·9H2O:
C47.32,H6.53,N9.35
实验值:C47.08,H6.66,N9.25
实施例39
IR(KBr):3350,1670.1,1631.5,1510.0,1234.2cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.7Hz),0.96(3H,d,
J=6.7Hz),1.06(3H,d,J=5.6Hz),1.2-1.5(8H,m),
1.6-2.1(5H,m),2.1-2.7(4H,m),3.0-3.3(5H,m),
3.3-3.5(4H,m),3.6-3.8(2H,m),3.88(2H,d,
J=6.4Hz),3.8-4.5(11H,m),4.7-5.1(8H,m),5.10
(1H,d,J=5.6Hz),5.16(1H,d,J=3.1Hz),5.25(1H,
d,J=4.5Hz),5.48(1H,d,J=5.9Hz),6.73(1H,d,
J=8.2Hz),6.8-6.9(4H,m),6.94(2H,d,J=9.3Hz),
7.01(2H,d,J=8.7Hz),7.04(1H,s),7.2-7.5(3H,
m),7.81(2H,d,J=8.7Hz),8.06(1H,d,J=8Hz),
8.25(1H,d,J=6.7Hz),8.43(1H,d,J=6.7Hz),8.85
(1H,s)
FAB-MASS:m/z=1359(M+Na)
元素分析 理论值C59H81N10O22SNa·5H2O:
C49.64,H6.43,N9.81
实验值:C49.49,H6.54,N9.72
实施例40
IR(KBr):3355.5,1670.1,1627.6,1510.0 1236.1cm-1
NMR(DMSO-d6,δ): 0.89(6H,d,J=6.5Hz),0.96(3H,d,
J=6.7Hz),1.05(3H,d,J=5.7Hz),1.2-1.4(2H,m),
1.5-2.1(6H,m),2.1-2.7(4H,m),3.0-3.6(9H,m),
3.6-4.5(15H,m),4.5-5.4(12H,m),6.73(1H,d,
J=8.2Hz),6.8-6.9(4H,m),6.96(2H,d,J=9.6Hz),
7.02(2H,d,J=8.7Hz),7.05(1H,s),7.2-7.5(3H,
m),7.82(2H,d,J=8.7Hz),8.08(1H,d,J=8Hz),
8.27(1H,d,J=6.7Hz),8.46(1H,d,J=6.7Hz),8.85
(1H,s)
FAB-MASS:m/z=1345(M+Na)
元素分析 理论值C58H79N10O22SNa·8H2O:
C47.47,H6.52,N9.54
实验值:C47.47,H6.54,N9.51
实施例41
IR(KBr):3347.8,1668.1,1629.6,1510.0,1234.2cm-1
NMR(DMSO-d6,δ):0.89(3H,t,J=7.0Hz),0.96(3H,d,
J=6.7Hz),1.05(3H,d,J=5.8Hz),1.2-1.5(4H,m),
1.6-2.1(5H,m),2.1-2.7(4H,m),3.0-3.6(9H,m),
3.6-3.8(2H,m),3.8-4.5(13H,m),4.7-5.6(12H,
m),6.73(1H,d,J=8.2Hz),6.8-6.9(4H,m),6.96
(2H,d,J=8.7Hz),7.02(2H,d,J=9.0Hz),7.04(1H,
s),7.2-7.5(3H,m),7.82(2H,d,J=8.7Hz),8.07
(1H,d,J=8Hz),8.27(1H,d,J=6.7Hz),8.45(1H,d,
J=6.7Hz),8.85(1H,s)
FAB-MASS:m/z=1331(M+Na)
元素分析 理论值C57H77N10O22SNa·6H2O:
C48.30,H6.33,N9.88
实验值:C48.20,H6.58,N10.03
实施例42
混合产物
IR(KBr):3344,1670.1,1631.5cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.7Hz),1.08(3H,d,
J=5.9Hz),1.2-1.5(8H,m),1.6-2.1(7H,m),2.1-2.7
(4H,m),3.1-3.3(1H,m),3.6-4.5(15H,m),4.45
and 4.70(2H,t,J=7.1Hz),4.6-5.3(11H,m),5.52
(1H,d,J=5.9Hz),6.73(1H,d,J=8.2Hz),6.83(1H,
d,J=8.2Hz),6.85(1H,s),7.03(2H,d,J=8.6Hz),
7.05(1H,s),7.2-7.5(3H,m),7.68(2H,d,
J=8.6Hz),7.71(2H,d,J=8.4Hz),7.96(2H,d,
J=8.4Hz),8.12(1H,d,J=8.5Hz),8.30(1H,d,
J=7.0Hz)
FAB-MASS:m/z=1357(M+Na)
元素分析 理论值C57H75N12O22SNa·4H2O:
C48.64,H5.94,N11.94
实验值:C48.91,H5.88,N11.86
实施例43
IR(KBr):3350,1666.2,1651.5cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.7Hz),1.05(6H,d,
J=6.3Hz),1.06(3H,d,J=5.7Hz),1.2-1.6(10H,m),
1.6-2.1(7H,m),2.1-2.7(6H,m),2.8-3.0(2H,m),
3.0-3.2(1H,m),3.4-3.7(2H,m),3.6-3.8(2H,m),
3.8-4.5(13H,m),4.7-5.6(12H,m),6.73(1H,d,
J=8.2Hz),6.8-7.0 (2H,m),7.03(2H,d,J=8.7Hz),
7.06(1H,s),7.2-7.5(3H,m),7.67(2H,d,
J=8.7Hz),7.71(2H,d,J=8.4Hz),7.96(2H,d,
J=8.4Hz),8.04(1H,d,J=8.5Hz),8.31(1H,d,
J=8.5Hz),8.73(1H,d,J=7.0Hz),8.90(1H,s)
FAB-MASS:m/z=1402(M+Na)
实施例44
IR(KBr压片):3350,2929,2856,1670,1631,1510,
1243,1045cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.8Hz),0.96(3H,d,
J=6.7Hz),1.06(3H,d,J=5.7Hz),1.6-2.0(5H,m),
2.2-2.5(5H,m),2.6-2.7(1H,m),3.0-3.3(5H,m),
3.6-4.5(19H,m),4.77(2H,d,J=5.9Hz),4.8-5.1
(6H,m),5.10(1H,d,J=5.6Hz),5.17(1H,d,
J=3.1Hz),5.25(1H,d,J=4.5Hz),5.50(1H,d,
J=5.8Hz),6.7-7.0(8H,m),7.04(1H,s),7.2-7.4
(3H,m),8.0-8.2(2H,m),8.26(1H,d,J=8.0Hz),
8.55(1H,d,J=7.3Hz),8.67(1H,d,J=1.2Hz),8.85
(1H,s)
FAB-MASS:m/z=1374.3(M+Na+)
元素分析 理论值C59H82N11O22NaS·5.5H2O:
C48.82,H6.46,N10.61
实验值:C48.89,H6.74,N10.50
实施例45
IR(KBr):3350,2935,1668,1623,1538,1257,1174,
1047cm-1
NMR(DMSO-d6,δ):0.8-1.1(6H,m),1.09(3H,d,
J=5.7Hz),1.2-1.6(6H,m),1.7-2.1(5H,m),2.2-2.4
(3H,m),2.5-2.6(1H,m),3.6-3.8(2H,m),3.8-4.6
(14H,m),4.8-5.2(7H,m),5.18(1H,d,J=3.1Hz),
5.26(1H,d,J=4.5Hz),5.54(1H,d,J=5.8Hz),6.7-
7.5(9H,m),7.82(1H,d,J=8.5Hz),7.96(1H,d,
J=8.7Hz),8.1-8.4(5H,m),8.8-9.0(2H,m)
FAB-MASS:m/z=1302.6(M+Na+)
元素分析 理论值C55H70N9O23SNa·6H2O:
C47.58,H5.95,N9.08
实验值:C47.46,H6.04,N9.05
实施例46
IR(KBr):3355,2958,1670,1627,1521,1247,
1047cm-1
NMR(DMSO-d6,δ):0.9-1.0(6H,m),1.08(3H,d,
J=5.6Hz),1.4-1.6(2H,m),1.7-2.1(5H,m),2.1-2.4
(3H,m),2.5-2.6(1H,m),3.1-3.3(1H,m),3.7-3.8
(2H,m),3.9-4.6(13H,m),4.8-5.1(8H,m),5.11
(1H,d,J=5.6Hz),5.17(1H,d,J=3.1Hz),5.26(1H,
d,J=4.5Hz),5.54(1H,d,J=5.9Hz),6.7-6.9(3H,
m),7.0-7.2(3H,m),7.3-7.5(3H,m),7.7-7.9(8H,
m),8.02(2H,d,J=8.4Hz),8.08(1H,d,J=8.4Hz),
8.32(1H,d,J=7.7Hz),8.81(1H,d,J=7.0Hz),8.85
(1H,s)
FAB-MASS:m/z=1309.3(M+Na)+
元素分析 理论值C58H71N8O22NaS·6H2O:
C49.92,H6.00,N8.03
实验值:C49.92,H5.97,N8.03
实施例47
IR(KBr):3350,2933,1668,1629,1517,1249,
1045cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.7Hz),0.96(3H,d,
J=6.7Hz),1.08(3H,d,J=5.8Hz),1.7-2.7(8H,m),
3.1-3.3(1H,m),3.6-4.5(16H,m),4.7-5.2(8H,m),
5.18(1H,d,J=3.1Hz),5.27(1H,d,J=4.5Hz),5.56
(1H,d,J=5.8Hz),6.7-7.0(3H,m),7.0-7.2(3H,m),
7.2-7.5(3H,m),8.0-8.4(6H,m),8.85(1H,s),
8.96(1H,d,J=7.0Hz),9.07(1H,s)
FAB-MASS:m/z=1276.6(M+Na+)
元素分析 理论值C54H72N9O22NaS·5H2O:
C48.25,H6.15,N9.38
实验值:C48.10,H6.14,N9.30
实施例48
IR(KBr):3350,2931,1668,1629,1537,1049cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.9Hz),0.9-1.5
(16H,m),1.6-2.4(8H,m),2.5-2.7(1H,m),3.1-3.3
(1H,m),3.5-5.6(25H,m),6.6-7.4(8H,m),7.8-8.4
(6H,m),8.7-9.0(2H,m),9.00(1H,d,J=2.4Hz)
FAB-MASS:m/z=1331.4(M+Na+)
元素分析 理论值C56H73N10O23NaS·8H2O:
C46.28,H6.17,N9.64
实验值:C46.50,H6.27,N9.65
实施例49
IR(KBr压片):3300,2931,1668,1650,1629,1538,
1515,1268,1049cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.6Hz),0.97(3H,d,
J=6.7Hz),1.10(3H,d,J=5.6Hz),1.2-1.4(6H,m),
1.5-1.7(2H,m),1.7-2.1(3H,m),2.1-2.4(3H,m),
2.6-2.7(3H,m),3.1-3.2(1H,m),3.7-3.9(2H,m),
3.9-4.5(12H,m),4.8-5.1(7H,m),5.11(1H,d,
J=5.5Hz),5.18(1H,d,J=3.1Hz),5.27(1H,d,
J=4.5Hz),5.55(1H,d,J=5.8Hz),6.7-7.0(3H,m),
7.06(1H,s),7.3-7.5(5H,m),7.72(2H,d,
J=8.2Hz),7.9-8.2(5H,m),8.3-8.4(4H,m),8.9-9.0
(2H,m)
FAB-MASS:m/z=1260.5(M+Na+)
元素分析 理论值C61H74N9O22SNa·6H2O:
C50.58,H5.98,N8.70
实验值:C50.34,H6.16,N8.55
实施例50
IR(KBr):3369,2958,2935,1670,1629,1525,1473,
1247,1047cm-1
NMR(DMSO-d6,δ):0.95(3H,t,J=7.3Hz),0.97(3H,d,
J=6.7Hz),1.09(3H,d,J=5.7Hz),1.3-1.6(2H,m),
1.7-2.1(5H,m),2.1-2.4(3H,m),2.5-2.6(1H,m),
3.1-3.3(1H,m),3.7-4.6(15H,m),4.7-5.1(8H,m),
5.10(1H,d,J=5.6Hz),5.18(1H,d,J=3.1Hz),5.26
(1H,d,J=4.4Hz),5.56(1H,d,J=5.7Hz),6.7-7.0
(3H,m),7.1-7.2(3H,m),7.2-7.4(3H,m),7.70
(2H,d,J=8.6Hz),7.78(2H,d,J=8.4Hz),8.1-8.4
(6H,m),8.85(1H,s),8.99(1H,d,J=7.0Hz),9.13
(1H,d,J=1.6Hz)
FAB-MASS:m/z=1310.1(M+Na)+
元素分析 理论值C57H70N9O22NaS·7H2O:
C47.20,H6.12,N8.69
实验值:C47.42,H6.19,N8.92
实施例51
IR(KBr):3351,2937,2875,1670,1627,1533,1245,
1047cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.7Hz),1.08(3H,
d,J=5.7Hz),1.5-1.7(2H,m),1.7-2.1(7H,m),2.1-
2.4(3H,m),2.5-2.6(1H,m),3.1-3.2(1H,m),3.7-
3.8(2H,m),3.9-4.6(15H,m),4.7-4.9(3H,m),
5.0-5.1(5H,m),5.10 (1H,d,J=5.6Hz),5.17(1H,
d,J=3.1Hz),5.26(1H,d,J=4.5Hz),5.52(1H,d,
J=5.9Hz),6.7-7.1(9H,m),7.2-7.5(5H,m),7.68
(2H,d,J=8.2Hz),7.72(2H,d,J=6.7Hz),7.96(2H,
d,J=8.2Hz),8.06(1H,d,J=8.4Hz),8.28(1H,d,
J=7.7Hz),8.76(1H,d,J=7.0Hz),8.85(1H,s)
FAB-MASS:m/z=1339.5(M+Na+)
元素分析 理论值C59H73N8O23NaS·7H2O:
C49.09,H6.08,N7.76
实验值:C49.04,H6.08,N7.82
实施例52
IR(KBr):3350,2954,2937,1670,1631,1440,1257,
1047cm-1
NMR(DMSO-d6,δ):0.89(3H,t,J=6.8Hz),0.97(3H,d,
J=6.7Hz),1.09(2H,d,J=5.8Hz),1.2-1.5(6H,m),
1.7-2.1(5H,m),2.1-2.4(3H,m),2.5-2.6(1H,m),
3.1-3.2(1H,m),3.7-4.6(15H,m),4.7-5.3(11H,
m),5.5-5.6(1H,m),6.7-6.9(1H,m),7.0-7.5(6H,
m),8.0-8.4(8H,m),8.85(1H,s),8.96(1H,d,
J=7.0Hz)
APCI-MASS:m/z=1329.0.(M+Na)+
元素分析 理论值C56H71N10O23NaS·6H2O:
C47.52,H5.91,N9.90
实验值:C47.42,H6.05,N9.90
实施例53
IR(KBr):3350,2952,1666,1629,1537,1519,
1255cm-1
NMR(DMSO-d6,δ):0.89(3H,t,J=6.7Hz),0.96(3H,d,
J=6.4Hz),1.08(3H,d,J=5.6Hz),1.7-2.4(8H,m),
2.5-2.6(1H,m),3.7-4.5(15H,m),4.7-5.1(8H,m),
5.11(1H,d,J=5.5Hz),5.17(1H,d,J=3.1Hz),5.26
(1H,d,J=3.1Hz),5.56(1H,d,J=5.7Hz),6.73(1H,
d,J=8.2Hz),6.7-7.0(2H,m),7.05(1H,s),7.13
(2H,d,J=8.7Hz),7.2-7.5(3H,m),7.97(2H,d,
J=8.7Hz),8.1-8.4(6H,m),8.85(1H,s),8.92(1H,
d,J=7.0Hz)
FAB-MASS:m/z=1345.3(M+Na)+
元素分析 理论值
C56H71N10O22S2Na·8H2O:
C45.84,H5.98,N9.55
实验值:C45.87,H6.07,N9.55
实施例54
IR(KBr pelet):3350,2931,1670,1652,1628,1442,
1247,1047cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.6Hz),0.97(3H,d,
J=6.8Hz),1.12(3H,d,J=6.8Hz),1.2-1.5(10H,m),
1.7-2.0(5H,m),2.2-2.4(3H,m),2.5-2.6(1H,m),
3.1-3.2(1H,m),3.72(2H,br),3.8-4.5(17H,m),
4.7-5.2(9H,m),5.26(1H,d,J=4.6Hz),5.57(1H,
d,J=5.7Hz),6.7-7.1(7H,m),7.3-7.5(3H,m),7.66
(2H,d,J=8.7Hz),8.10(1H,d,J=7.6Hz),8.17(1H,
d,J=7.6Hz),8.76(1H,d,J=7.0Hz),8.85(1H,s)
FAB-MASS:m/z=1293(M+Na+)
元素分析 理论值C54H75N10O22NaS·7H2O:
C46.41,H6.42,N10.02
实验值:C46.51,H6.43,N9.95
实施例55
IR(KBr):3345,2937,1650,1511,1249,1047cm-1
NMR(DMSO-d6,δ):0.91(3H,t,J=7.0Hz),0.96(3H,t,
J=7.8Hz),1.09(3H,d,J=6.8Hz),1.3-1.5(4H,m),
1.6-2.1(5H,m),2.1-2.5(3H,m),2.5-2.6(1H,m),
3.1-3.3(1H,m),3.7-3.9(2H,m),3.9-4.6(13H,m),
4.79(2H,d,J=5.9Hz),4.8-4.9(1H,m),4.9-5.2
(5H,m),5.10(1H,d,J=5.9Hz),5.17(1H,d,
J=3.1Hz),5.25(1H,d,J=4.6Hz),5.53(1H,d,
J=5.9Hz),6.7-7.0(3H,m),7.0-7.2(3H,m),7.19
(1H,s),7.3-7.5(3H,m),7.7-8.1(6H,m),8.08
(1H,d,J=10.0Hz),8.26(1H,d,J=8.8Hz),8.77(1H,
m),8.85(1H,s),13.32(1H,s)
FAB-MASS:m/z=1314.0(M+Na)+
元素分析 理论值C56H71N10O22SNa·8H2O:
C46.86,H6.11,N9.76
实验值:C46.93,H5.87,N9.74
实施例56
IR(KBr):3350,2958,2935,2873,1666,1629,1247,
1045cm-1
NMR(DMSO-d6,δ):0.9-1.1(6H,m),1.08(3H,d,
J=6.0Hz),1.4-1.6(2H,m),1.6-2.1(5H,m),2.1-2.4
(3H,m),2.5-2.6(1H,m),3.1-3.3(1H,m),3.6-4.5
(15H,m),4.7-5.1(8H,m),5.10(1H,d,J=5.5Hz),
5.17(1H,d,J=2.9Hz),5.25(1H,d,J=4.5Hz),5.55
(1H,d,J=5.7Hz),6.7-6.9(3H,m),7.0-7.5(8H,m),
7.68(2H,d,J=8.9Hz),7.73(2H,d,J=8.3Hz),8.01
(2H,d,J=8.3Hz),8.10(1H,d,J=8.4Hz),8.26(1H,
d,J=7.7Hz),8.8-9.0(2H,m)
FAB-MASS:m/z=1299.5(M+Na)+
元素分析 理论值C56H69N8O23NaS·6H2O:
C48.55,H5.89,N8.09
实验值:C48.52,H5.94,N8.07
实施例57
IR(KBr):3355.5,1662.3,1629.6,1267.0cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.8Hz),0.93(3H,d,
J=8.4Hz),0.97(3H,d,J=6.7Hz),1.2-1.5(4H,m),
1.5-1.95(5H,m),2.1-2.45(4H,m),2.5-2.7(4H,
m),3.17(1H,m),3.55-4.45(14H,m),4.6-5.3(13H,
m),5.56(1H,d,J=5.6Hz),6.72(1H,d,J=8.1Hz),
6.75(1H,s),6.77(1H,d,J=8.1Hz),7.04(1H,s),
7.10(1H,s),7.2-7.45(10H,m),7.53(4H,d,
J=6.6Hz),7.85(1H,d,J=7Hz),7.92(1H,d,J=7Hz),
8.05(1H,d,J=7Hz),8.22(1H,d,J=7Hz),8.84(1H,
s)
FAB-MASS:m/z=1408(M+Na)
实施例58
IR(KBr):3347.8,1664.3,1631.5,1245.8cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.6Hz),0.96(3H,d,
J=6.6Hz),1.04(3H,d,J=5.7Hz),1.15-2.6(21H,
m),3.16(1H,m),3.5-4.5(16H,m),4.6-5.4(13H,
m),5.47(1H,d,J=5.7Hz),6.73(1H,d,J=8.2Hz)
6.78-6.85(4H,m),7.05(1H,s),7.10(1H,s),7.18
(2H,d,J=8.6Hz),7.25-7.45(6H,m),7.72(1H,d,
J=7Hz),7.91(1H,d,J=7Hz),8.05(1H,d,J=9.3Hz),
8.20(1H,d,J=7Hz),8.85(1H,s)
FAB-MASS:m/z=1390(M+Na)
元素分析 理论值C60H82N9O24SNa·5H2O:
C49.41,H6.36,N8.64
实验值:C49.77,H6.71,N8.71
实施例59
IR(KBr):3353.6,1670.1,1627.6,1247.7cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.5Hz),0.97(3H,d,
J=6.8Hz),1.01(3H,d,J=5.4Hz),1.1-1.55(12H,m),
1.55-1.95(5H,m),2.05-4.7(4H,m),3.16(1H,m),
3.5-4.5(16H,m),4.6-5.3(13H,m),5.55(1H,d,
J=5.6Hz),6.7-6.9(5H,m),7.05(1H,s),7.1(1H,
s),7.15(1H,d,J=8.5Hz),7.25-7.5(6H,m),7.73
(1H,d,J=8.4Hz),7.92(1H,d,J=7Hz),8.08(1H,d,
J=8.4Hz),8.18(1H,d,J=7Hz),8.84(1H,s)
FAB-MASS:m/z=1390(M+Na)
实施例60
NMR(DMSO-d6,δ):0.85(3H,t,J=6.6Hz),0.96(3H,d,
J=6.6Hz),1.05(3H,d,J=5.6Hz),1.1-1.5(22H,m),
1.5-2.5(9H,m),2.5-3.5(4H,m),3.5-4.45(14H,
m),4.45-5.45(12H,m),6.72(1H,d,J=8.2Hz),6.79
(1H,s),6.81(1H,d,J=8.2Hz),7.04(1H,s),7.05-
7.5(8H,m),7.9-8.3(3H,m),8.84(1H,s)
FAB-MASS:m/z=1325(M+Na)
元素分析 理论值C58H89N8O22SNa·6H2O:
C49.35,H7.14,N7.94
实验值:C49.33,H7.04,N7.87
实施例61
IR(KBr):3400,1668.1,1629.6,1270.9cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.8Hz),1.06(3H,d,
J=5.7Hz),1.1-2.0(33H,m),2.1-2.5(4H,m),3.20
(3H,s),3.28(2H,t,J=6.5Hz),3.1-3.3(1H,m),
3.6-4.45(14H,m),4.6-5.3(13H,m),5.49(1H,d,
J=6.1Hz),6.70(1H,s),6.72(1H,d,J=8.2Hz),6.80
(1H,d,J=8.2Hz),7.03(1H,s),7.0-7.1(1H,m),
7.15(1H,s),7.2-7.45(6H,m),8.0-8.3(3H,m),
8.83(1H,s)
FAB-MASS:m/z=1426(M+Na)
元素分析 理论值C62H94N9O24SNa·5H2O:
C49.82,H7.01,N8.43
实验值:C49.86,H7.31,N8.40
实施例62
IR(KBr):3355.5,1668.1,1629.6,1274.7cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.5Hz),0.96(3H,d,
J=6.7Hz),1.04(3H,d,J=5.9Hz),1.1-2.6(34H,m),
3.2(1H,m),3.6-4.55(14H,m),4.7-5.3(11H,m),
5.47(1H,d,J=5.9Hz),6.72(1H,d,J=8.1Hz),6.79
(1H,s),6.81(1H,d,J=8.1Hz),7.05(1H,s),7.11
(1H,s),7.2-7.5(2H,m),8.0-8.15(2H,m),8.20
(1H,d,J=8.0Hz),8.84(1H,s)
FAB-MASS:m/z=1235(M+Na)
元素分析 理论值C51H81N8O22SNa·7H2O:
C45.73,H7.15,N8.37
实验值:C45.55,H7.24,N8.23
实施例63
IR(KBr):3353.6,1664.3,1627.6cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.6Hz),0.95(3H,d,
J=6.7Hz),1.04(3H,d,J=5.7Hz),1.2-2.7(30H,m),
3.16(1H,m),3.6-4.5(13H,m),4.7-5.3(11H,m),
5.51(1H,d,J=6.0Hz),5.74(1H,s),6.72(1H,d,
J=8.2Hz),6.75(1H,s),6.77(1H,d,J=8.2Hz),7.05
(1H,s),7.2-7.5(3H,m),8.0-8.3(3H,m),8.85
(1H,s)
FAB-MASS:m/z=1204(M+Na)
元素分析 理论值C50H77N8O21SNa·5H2O:
C47.24,H6.90,N8.81
实验值:C46.98,H7.12,N8.72
实施例64
主产物
IR(KBr):3400,1675.8,1631.5,1511.9,1234.2cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.6Hz),1.05(3H,d,
J=5.8Hz),1.2-1.6(10H,m),1.6-2.1(5H,m),2.1-
2.7(4H,m),3.05-3.2(4H,m),3.20(3H,s),3.29
(2H,t,J=6.4Hz),3.3-3.5(5H,m),3.6-4.5(15H,
m),4.7-5.3(11H,m),5.50(1H,d,J=5.8Hz),6.73
(1H,d,J=8.2Hz),6.8-7.1(9H,m),7.2-7.5(3H,m),
7.81(2H,d,J=8.6Hz),8.08(1H,d,J=8.2Hz),8.24
(1H,d,J=7Hz),8.44(1H,d,J=7Hz),8.84(1H,s)
FAB-MASS:m/z=1403(M+Na)
元素分析 理论值C61H85N10O23SNa·9H2O:
C47.47,H6.73,N9.07
实验值:C47.43,H7.06,N9.03
次产物
IR(KBr):3350,1668.1,1631.5,1511.9,1234.2cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.6Hz),1.07(3H,d,
J=5.8Hz),1.2-1.5(6H,m),1.55-2.1(7H,m),2.1-
2.65(4H,m),3.0-3.6(9H,m),3.7-4.5(15H,m),
4.7-5.6(14H,m),5.7-6.0(1H,m),6.72(1H,d,
J=8.0Hz),6.75-7.1(9H,m),7.25-7.5(3H,m),7.81
(2H,d,J=8.3Hz),8.08(1H,d,J=8.2Hz),8.25(1H,
d,J=7Hz),8.45(1H,d,J=7Hz),8.85(1H,s)
FAB-MASS:m/z=1371(M+Na)
元素分析理论值C60H81N10O22SNa·8H2O:
C48.25,H6.55,N9.38
实验值:C48.10,H6.81,N9.40
实施例65
IR(KBr):3450,1668.1,1635.3cm-1
NMR(DMSO-d6,6):0.88(3H,t,J=6.5Hz),0.96(3H,d,
J=6.7Hz),1.06(3H,d,J=6Hz),1.2-1.5(6H,m),
1.6-2.1(5H,m),2.1-2.7(4H,m),3.1-3.4(9H,m),
3.6-4.5(15H,m),4.7-5.3(11H,m),5.49(1H,d,
J=5.8Hz),6.73(1H,d,J=8.2Hz),6.8-7.0(2H,m),
6.83(2H,d,J=9.0Hz),6.94(2H,d,J=9.0Hz),7.04
(1H,s),7.12(1H,t,J=8.4Hz),7.2-7.5(3H,m),
7.65-7.8(2H,m),8.09(1H,d,J=8.4Hz),8.25(1H,
d,J=7Hz),8.63(1H,d,J=7Hz),8.84(1H,s)
FAB-MASS:m/z=1363(M+Na)
元素分析 理论值C58H78FN10O22SNa·5H2O:.
C48.67,H6.20,N9.79
实验值:C48.83,H6.15,N9.74
实施例66
IR(KBr):3400,1668.1,1635.3,1510.0,1240.0cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.6Hz),1.2-1.5(6H,
m),1.5-2.05(5H,m),2.1-2.65(4H,m),3.1-3.3
(9H,m),3.6-4.5(15H,m),4.7-5.3(11H,m),5.51
(1H,d,J=5.8Hz),6.73(1H,d,J=8.2Hz),6.8-6.9
(4H,m),6.94(2H,d,J=9.2Hz),7.04(1H,s),7.24
(1H,d,J=8.5Hz),7.15-7.5(3H,m),7.86(1H,dd,
J=8.6 and 2.1Hz),8.02(1H,d,J=2.1Hz),8.04(1H,
d,J=8.4Hz),8.23(1H,d,J=7Hz),8.70(1H,d,
J=7Hz),8.84(1H,s)
FAB-MASS:m/z=1379(M+Na)
元素分析 理论值C58H78ClN10O22SNa·6H2O:
C47.52,H6.19,N9.55
实验值:C47.78,H6.23,N9.55
实施例67
IR(KBr):3400,1670cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.7Hz),1.05(3H,d,
J=5.7Hz),1.4-2.65(17H,m),2.65-3.6(8H,m),3.6-
4.5(15H,m),4.6-5.3(11H,m),5.44(1H,d,
J=6.0Hz),6.73(1H,d,J=8.2Hz),6.81(1H,s),6.83
(1H,d,J=8.2Hz),6.98(2H,d,J=8.9Hz),7.05(1H,
s),7.2-7.5(3H,m),7.80(2H,d,J=8.9Hz),8.05
(1H,d,J=8.4Hz),8.26(1H,d,J=7Hz),8.39(1H,d,
J=7Hz),8.84(1H,s)
FAB-MASS:m/z=1229(M+Na)
元素分析 理论值C52H74N10O21S5·H2O:
C48.14,H6.53,N10.80
实验值:C48.29,H6.33,N10.95
实施例68
IR(KBr):3400,1652.7,1635.3,1511.9,1241.9cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.6Hz),0.97(3H,d,
J=6.7Hz),1.09(3H,d,J=5.7Hz),1.2-1.5(6H,m),
1.6-2.0(5H,m),2.1-2.6(4H,m),3.0-3.3(5H,m),
3.6-4.6(19H,m),4.7-5.3(11H,m),5.53(1H,d,
J=5.6Hz),6.73(1H,d,J=8.2Hz),6.75-7.0(2H,m),
6.83(2H,d,J=9.2Hz),6.95(2H,d,J=9.2Hz),7.05
(1H,s),7.12(1H,s),7.25-7.5(2H,m),7.42(1H,
d,J=9.5Hz),7.84(1H,d,J=9.5Hz),7.9-8.1(2H,
m),8.71(1H,d,J=7Hz),8.84(1H,s)
FAB-MASS:m/z=1347(M+Na)
元素分析 理论值C56H77N12O22SNa·7H2O:
C46.34,H6.32,N11.58
实验值:C46.38,H6.18,N11.36
实施例69
NMR(DMSO-d6,δ):0.88(3H,t,J=6.6Hz),0.97(3H,d,
J=6.7Hz),1.08(3H,d,J=5.8Hz),1.2-1.5(6H,m),
1.6-2.05(5H,m),2.1-2.6(4H,m),3.0-3.3(5H,m),
3.4-3.55(4H,m),3.7-4.6(15H,m),4.7-5.3(11H,
m),5.52(1H,d,J=5.8Hz),6.73(1H,d,J=8.1Hz),
6.8-6.95(2H,m),6.83(2H,d,J=9.3Hz),6.95(2H,
d,J=9.3Hz)7.05(1H,s),7.14(1H,s),7.3-7.6
(3H,m),7.84(1H,d,J=8.6Hz),7.95-8.1(2H,m),
8.40(1H,s),8.42(1H,d,J=7Hz),8.84(1H,s)
FAB-MASS:m/z=1346(M+Na)
元素分析 理论值C57H78N11O22SNa·5H2O:
C48.40,H6.27,N10.89
实验值:C48.32,H6.44,N10.86
实施例70
NMR(DMSO-d6,δ):0.96(3H,d,J=6.7Hz),1.06(3H,d,
J=5.7Hz),1.15-1.5(6H,m),1.6-2.0(7H,m),2.1-
2.65(5H,m),3.1-3.5(9H,m),3.6-4.5(13H,m),
4.7-5.3(11H,m),5.46(1H,d,J=5.9Hz),6.73(1H,
d,J=8.2Hz),6.81(1H,s),6.84(1H,d,J=8.2Hz),
6.91(2H,d,J=8.7Hz),6.95-7.05(3H,m),7.09(2H,
d,J=8.7Hz),7.25-7.5(3H,m),7.81(2H,d,
J=8.8Hz),8.09(1H,d,J=7Hz),8.25(1H,d,J=7Hz),
8.04(1H,d,J=7Hz),8.84(1H,s)
FAB-MASS:m/z=1327(M+Na)
元素分析 理论值C58H77N10O21SNa·5H2O:
C49.92,H6.28,N10.03
实验值:C49.75,H6.41,N10.25
实施例71
IR(KBr):3350,1668.1,1629.6,1511.9,1232.3cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.5Hz),0.96(3H,d,
J=6.7Hz),1.06(3H,d,J=6.0Hz),1.2-1.4(6H,m),
1.4-1.6(2H,m),1.7-2.1(3H,m),2.1-2.7(6H,m),
3.1-3.5(9H,m),3.72(2H,m),3.8-4.5(11H,m),
4.7-5.3(11H,m),5.47(1H,d,J=5.9Hz),6.73(1H,
d,J=8.2Hz),6.8-6.9(2H,m),6.91(2H,d,
J=8.6Hz),6.95-7.15(5H,m),7.25-7.5(3H,m),7.81
(2H,d,J=8.8Hz),8.09(1H,d,J=8.4Hz),8.26(1H,
d,J=7Hz),8.40(1H,d,J=7Hz),8.84(1H,s)
FAB-MASS:m/z=1329(M+Na)
元素分析 理论值C58H79N10NaO21S·6H2O:
C49.22,H6.48,N9.90
实验值:C49.33,H6.67,N9.89
实施例72
IR(KBr):3450,1668.1,1631.5,1240.0cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.6Hz),1.05(3H,d,
J=5.6Hz),1.3-1.7(4H,m),1.7-2.1(7H,m),2.1-
2.73(6H,m),2.75-3.05(4H,m),3.05-4.5(18H,m),
4.7-5.5(12H,m),6.72(1H,d,J=8.3Hz),6.77-6.9
(2H,m),6.96(2H,d,J=8.6Hz),7.05(1H,s),7.1-
7.5(8H,m),7.80(2H,d,J=8.6Hz),8.06(1H,d,
J=8.4Hz),8.28(1H,d,J=7Hz),8.41(1H,d,J=7Hz),
8.84(1H,s)
FAB-MASS:m/z=1305(M+Na)
元素分析 理论值C58H78N10O21S·8H2O:
C48.80,H6.64,N9.81
实验值:C48.88,H6.50,N9.81
实施例73
IR(KBr):1673.9,1646.9,1510.0 1238.1cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.4Hz),0.96(3H,d,
J=6.6Hz),1.05(3H,d,J=5.6Hz),1.2-1.5(6H,m),
1.5-2.0(9H,m),2.1-2.8(11H,m),3.1-3.4(5H,m),
3.4-4.5(17H,m),4.6-5.5(12H,m),6.6-7.0(9H,
m),7.04(1H,s),7.2-7.5(3H,m),7.78(2H,d,
J=8.7Hz),8.05(1H,d,J=8.4Hz),8.24(1H,d,
J=7Hz),8.39(1H,d,J=7Hz),8.84(1H,s)
FAB-MASS:m/z=1326(M+-SO3+Na)
元素分析 理论值C63H89N11O22S·9H2O:
C48.92,H6.97,N9.96
实验值:C48.77,H6.73,N9.94
实施例74
IR(KBr):3450,1670.1,1631.5,12 80.5cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=7.0Hz),0.96(3H,t,
J=6.8Hz),1.05(3H,d,J=5.6Hz),1.1-1.65(13H,m),
1.65-2.1(7H,m),2.1-2.65(5H,m),3.17(1H,m),
3.6-4.5(13H,m),4.7-5.3(11H,m),5.49(1H,d,
J=5.9Hz),6.72(1H,d,J=8.2Hz),6.82(1H,d,
J=8.2Hz),6.84(1H,s),7.04 (1H,s),7.29(2H,d,
J=8.3Hz),7.2-7.5(3H,m),7.80(2H,d,J=8.3Hz),
8.10(1H,d,J=8.4Hz),8.26(1H,d,J=7Hz),8.65
(1H,d,J=7Hz),8.84(1H,s)
FAB-MASS:m/z=1237(M+Na)
元素分析 理论值C53H75N8O21SNa·6H2O:
C48.10,H6.63,N8.47
实验值:C48.26,H6.62,N8.46
实施例75
IR(KBr):3400,1670.1,1627.6,1272.8cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=3.3Hz),1.08(3H,d,
J=5.7Hz),1.2-1.6(10H,m),1.6-2.1(5H,m),2.1-
2.7(4H,m),3.0-3.3(1H,m),3.20(3H,s),3.29
(2H,t,J=6.4Hz),3.73(2H,m),3.9-4.6(13H,m),
4.7-5.3(11H,m),5.53(1H,d,J=5.8Hz),6.73(1H,
d,J=8.3Hz),6.83(1H,d,J=8.3Hz),6.91(1H,s),
7.05(1H,s),7.23(1H,dd,J=9.0and2.3Hz),7.3-
7.5(4H,m),7.8-8.0(3H,m),8.09(1H,d,
J=8.4Hz),8.33(1H,d,J=7Hz),8.44(1H,s),8.80
(1H,d,J=7Hz),8.85(1H,s)
FAB-MASS:m/z=1293(M+Na)
元素分析 理论值C55H75N8O23SNa·6H2O:
C47.89,H6.36,N8.12
实验值:C47.81,H6.26,N8.05
实施例76
IR(KBr):3361.3,1668.1,1635.3,1627.6cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.7Hz),0.96(3H,d,
J=6.7Hz),1.09(3H,d,J=5.8Hz),1.19-1.25(8H,m),
1.25-2.00(5H,m),2.02-2.53(4H,m),2.44(3H,s),
2.61(2H,t,J=7.6Hz),3.05-3.27(1H,m),3.55-4.50
(13H,m),4.65-5.65(12H,m),6.42(1H,s),6.65-
6.95(3H,m),7.05(1H,d,J=0.4Hz),7.13-7.50(5H,
m),7.50-7.88(6H,m),8.10(1H,d,J=9.0Hz), 8.25
(1H,d,J=8.4Hz),8.40(1H,d,J=7.0Hz),8.85(1H,
s)
FAB-MASS:m/z=1299.3(M+Na-1)
元素分析 理论值C58H77N8NaO21S·5H2O:
C50.94,H6.41,N8.19
实验值:C50.99,H6.40,N8.15
实施例77
IR(Nujol):3351.7,1670.1,1652.7,1623.8cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.7Hz),0.96(3H,d,
J=6.7Hz),1.06(3H,d,J=5.8Hz),1.13-1.45(8H,m),
1.47-1.96(5H,m),2.06-2.66(8H,m),2.81(2H,t,
J=7.6Hz),3.04-3.30(1H,m),3.53-4.50(13H,m),
4.53-5.70(12H,m),6.64-6.88(3H,m),7.04(1H,d,
J=0.4Hz),7.13-7.60(11H,m),8.10(1H,d,
J=9.0Hz),8.18(1H,d,J=8.4Hz),8.30(1H,d,
J=7.0Hz),8.85(1H,s)
FAB-MASS:m/z=1287.4(M+Na-1)
元素分析 理论值C57H77N8NaO21S·5H2O:
C50.51,H6.46,N8.27
实验值:C50.84,H6.60,N8.33
实施例78
IR(KBr):3361.3,1683.6,1670.1,1662.3,1652.7,
1646.9,1635.3,1627.6,1623.8cm-1
NMR(DMSO-d6,δ):0.97(3H,d,J=6.7Hz),1.07(3H,d,
J=5.6Hz),1.28-2.00(13H,m),2.08-2.60(4H,m),
3.07-3.30(1H,m),3.60-4.66(17H,m),4.66-5.12
(9H,m),5.11(1H,d,J=3.1Hz),5.25(1H,d,
J=4.6Hz),5.52(1H,d,J=6.0Hz),6.62-6.95(4H,m),
6.95-7.15(3H,m),7.20-7.50(3H,m),7.50-7.85
(7H,m),8.12(1H,d,J=8.4Hz),8.35(1H,d,
J=7.7Hz),8.53(1H,d,J=7.0Hz),8.85(1H,s)
FAB-MASS:m/z=1319.7(M+Na-1)
元素分析 理论值C57H74N8NaO22SF·8H2O:
C47.49,H6.29,N7.77
实验值:C47.79,H6.16,N7.93
实施例79
IR(KBr):3354.9,1668.1,1662.3,1654.6,1646.9,
1627.6cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.7Hz),0.90-1.10
(6H,m),1.10-1.40(8H,m),1.48-1.95(5H,m),
2.05-2.46(4H,m),2.60(2H,t,J=7.6Hz),3.07-3.23
(1H,m),3.55-4.45(14H,m),4.67-5.32(11H,m),
5.48-5.63(1H,m),6.22(1H,,J=5.3Hz),6.65-6.89
(3H,m),6.97-7.15(2H,m),7.20-7.68(10H,m),
7.85-8.20(3H,m),8.84(1H,s)
FAB-MASS:m/z=1289.4(M+Na-1)
元素分析 理论值C56H75N8NaO22S·3H2O:
C50.90,H6.18,N8.48
实验值:C50.80,H6.44,N8.29
实施例80
IR(KBr):3361.3,1664.3,1631.5,1600.6cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.7Hz),0.98(3H,d,
J=6.7Hz),1.16(3H,t,J=5.9Hz),1.20-1.45(8H,m),
1.50-1.70(2H,m),1.70-2.05 (3H,m),2.10-2.57
(4H,m),2.63(2H,t,J=7.6Hz),3.10-3.30(1H,m),
3.68-4.50(13H,m),4.7 8-5.32(11H,m),5.66(1H,
d,J=5.7Hz),6.68-7.02(3H,m),7.04(1H,c,
J=0.4Hz),7.25-7.48(4H,m),7.60-8.08(7H,m),
8.10(1H,d,J=8.4Hz),8.28(1H,d,J=7.7Hz),8.85
(1H,s),9.30(1H,d,J=7.1Hz)
FAB-MASS:m/z=1287.5(M+Na-1)
元素分析 理论值C55H73N8NaO22S·3H2O:
C50.53,H6.09,N8.57
实验值:C50.66,H6.01,N8.22
实施例81
IR(KBr):3349.7,1668.1,1627.6cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.7Hz),0.96(3H,d,
J=6.7Hz),1.09(3H,d,J=5.8Hz),1.18-1.48(8H,m),
1.50-2.10(5H,m),2.10-2.45(3H,m),2.50-2.65
(1H,m),2.77(2H,t,J=7.6Hz),3.05-3.25(1H,m),
3.60-4.65(13H,m),4.67-5.60(12H,m),6.65-6.97
(3H,m),7.05(1H,d,J=0.4Hz),7.21-7.43(4H,m),
7.76(1H,s),7.83-8.05(3H,m),8.10(1H,d,
J=9.0Hz),8.29(1H,d,J=8.4Hz),8.48(1H,s),
8.64-9.03(2H,m)
FAB-MASS:m/z=1233.0(M+Na-1)
元素分析 理论值C53H71N8NaO20S·3H2O:
C50.96,H6.22,N8.96
实验值:C50.62,H6.40,N8.92
实施例82
IR(KBr):3361.3,1670.1,1627.6cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=6.7Hz),0.96(3H,d,
J=6.7Hz),1.09(3H,d,J=5.9Hz),1.18-1.43(6H,m),
1.50-2.10(5H,m),2.10-2.69(4H,m),2.77(2H,t,
J=7.6Hz),3.07-3.29(1H,m),3.60-4.62(13H,m),
4.69-5.23(10H,m),5.27(1H,d,J=4.5Hz),5.55
(1H,d,J=5.9Hz),6.68-7.00(3H,m),7.05(1H,d,
J=0.4Hz),7.25-7.53(4H,m),7.76(1H,s),7.84-
8.05(3H,m),8.13(1H,d,J=8.4Hz),8.33(1H,d,
J=7.7Hz),8.48(1H,s),8.7 3-9.00(2H,m)
FAB-MASS:m/z=1219.4(M+Na-1)
元素分析 理论值C52H69N8NaO21S·5H2O:
C48.51,H6.19,N8.71
实验值:C48.67,H6.34,N8.74
实施例83
IR(KBr):3357.5,1668.1,1627.6cm-1
NMR(DMSO-d6,δ):0.97(3H,d,J=6.7Hz),1.07(3H,d,
J=6.0Hz),1.20-1.62(10H,m),1.62-2.00(5H,m),
2.10-2.65(4H,m),3.20(3H,s),3.08-3.45(1H,m),
3.28(2H,t,J=6.5Hz),3.53-4.50(15H,m),4.68-
5.13(9H,m),5.17(1H,d,J=3.1Hz),5.25(1H,d,
J=4.4Hz),5.53(1H,d,J=6.0Hz),6.68-6.95(4H,m),
6.95-7.11(3H,m),7.20-7.52(3H,m),7.55-7.95
(7H,m),8.13(1H,d,J=8.4Hz),8.30(1H,d,
J=7.7Hz),8.52(1H,d,J=7.0Hz),8.85(1H,s)
FAB-MASS:m/z=1345.2(M+Na-1)
元素分析 理论值C59H79N8NaO23S·8H2O:
C48.29,H6.53,N7.64
实验值:C48.44,H6.58,N7.75
实施例84
IR(KBr):3353.6,1662.3,1627.6cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.7Hz),1.07(3H,d,
J=5.5Hz),1.40-1.65(2H,m),1.65-2.00(5H,m),
2.00-2.67(6H,m),3.08-3.30(1H,m),3.50-4.50
(15H,m),4.68-5.13(11H,m),5.18(1H,d,
J=3.1Hz),5.26(1H,d,J=4.5Hz),5.53(1H,d,
J=6.0Hz),5.70-6.00(1H,m),6.63-6.95(4H,m),
6.95-7.13(3H,m),7.20-7.52(3H,m),7.52-7.95
(7H,m),8.12(1H,d,J=8.4Hz),8.31(1H,d,
J=7.7Hz),8.53(1H,d,J=7.0Hz),8.85(1H,s)
FAB-MASS:m/z=1285.4(M+Na-1)
元素分析 理论值C56H71N8O22SNa·8H2O:
C47.79,H6.23,N7.96
实验值:C47.59,H6.32,N8.06
实施例85
IR(KBr):3363.2,1670.1,1627.6cm-1
NMR(DMSO-d6,δ):0.89(6H,d,J=6.5Hz),0.96(3H,
d,J=6.7Hz),1.07(3H,d,J=5.7Hz),1.22-1.41(2H,
m),1.50-1.97(6H,m),2.11-2.65(4H,m),3.10-3.30
(1H,m),3.60-4.50(15H,m),4.70-5.08(8H,m),
5.10(1H,d,J=5.6Hz),5.16(1H,d,J=3.1Hz),5.25
(1H,d,J=4.5Hz),5.50(1H,d,J=5.9Hz),6.65-6.92
(4H,m),6.92-7.12(3H,m),7.21-7.50(3H,m),
7.52-7.90(7H,m),8.12(1H,d,J=8.4Hz),8.30(1H,
d,J=7.7Hz),8.56(1H,d,J=7.0Hz),8.85(1H,s)
FAB-MASS:m/z=1287.6(M+Na-1)
元素分析 理论值C56H73N8NaO22S·6.5H2O:
C48.66,H6.27,N8.11
实验值:C48.67,H6.32,N8.20
实施例86
IR(KBr):3361.3,1683.6,1670.1,1654.6,1635.3,
1623.8cm-1
NMR(DMSO-d6,δ):0.97(3H,d,J=6.7Hz),1.07(3H,d,
J=5.6Hz),1.30-2.00(11H,m),2.10-2.70(4H,m),
3.05-3.15(1H,m),3.55-4.70(17H,m),4.70-5.11
(9H,m),5.16(1H,d,J=3.1Hz),5.25(1H,d,
J=4.5Hz),5.52(1H,d,J=6.0Hz),6.65-6.95(4H,m),
6.95-7.10(3H,m),7.10-7.50(3H,m),7.50-7.85
(7H,m),8.12(1H,d,J=8.4Hz),8.30(1H,d,
J=8.3Hz),8.52(1H,d,J=7.0Hz),8.85(1H,s)
FAB-MASS:m/z=1305.2(M+Na-1)
元素分析 理论值C56H72N8NaO22SF·6H2O:
C48.34,H6.09,N8.05
实验值:C48.47,H6.29,N7.95
实施例87
IR(KBr):3359.4,1668.1,1654.6,1625.7cm-1
NMR(DMSO-d6,δ):0.97(3H,d,J=6.7Hz),1.07(3H,d,
J=6.0Hz),1.22-1.62(6H,m),1.62-2.00(5H,m),
2.10-2.65(4H,m),3.20(3H,s),3.05-3.40(1H,m),
3.31(2H,t,J=6.5Hz),3.60-4.55(15H,m),4.65-
5.13(9H,m),5.16(1H,d,J=3.1Hz),5.26(1H,d,
J=4.4Hz),5.53(1H,d,J=6.0Hz),6.68-6.95(4H,m),
6.95-7.20(3H,m),7.20-7.58(3H,m),7.58-7.90
(7H,m),8.13(1H,d,J=8.4Hz),8.32(1H,d,
J=7.7Hz),8.53(1H,d,J=7.0Hz),8.85(1H,s)
FAB-MASS:m/z=1317.6(M+Na-1)
元素分析 理论值C57H75N8NaO23S·7H2O:
C48.16,H6.31,N7.88
实验值:C48.21,H6.60,N7.78
实施例88
IR(KBr):3350,2954,1668,1629,1538,1511,1454,
1249cm-1
NMR(DMSO-d6,δ):0.88(3H,t,J=7.1Hz),0.96(3H,d,
J=7.5Hz),1.08(2H,d,J=5.7Hz),1.2-1.5(6H,m),
1.6-2.4(8H,m),2.6-2.7(1H,m),3.1-3.3(1H,m),
3.6-4.5(19H,m),4.7-5.3(8H,m),6.73(1H,d,
J=8.2Hz),6.8-7.1(5H,m),7.19(1H,s),7.3-7.5
(3H,m),7.75(2H,d,J=8.7Hz),7.8-8.0(4H,m),
8.08(1H,d,J=8.9Hz),8.30(1H,d,J=7.7Hz),8.7-
9.0(3H,m)
FAB-MASS:m/z=1327(M+Na+)
元素分析 理论值C57H73N10O22NaS·9H2O:
C46.65,H6.25,N9.54
实验值:C46.95,H6.22,N9.55
实施例89
IR(KBr):3376,2931,2858,1662,1631,1521,1444,
1245,1047cm-1
NMR(DMSO-d6,δ):0.97(3H,d,J=6.7Hz),1.09(3H,d,
J=5.9Hz),1.3-1.6(6H,m),1.7-2.1(5H,m),2.2-2.4
(3H,m),2.5-2.6(1H,m),3.21(3H,s),3.2-3.4
(3H,m),3.6-4.5(16H,m),4.79(2H,d,J=6.0Hz),
4.9-5.2(5H,m),5.10(1H,d,J=3.6Hz),5.18(1H,
d,J=3.1Hz),5.26(1H,d,J=4.5Hz),5.53(1H,d,
J=6.0Hz),6.73(1H,d,J=8.2Hz),6.8-7.0(2H,m),
7.0-7.2(3H,m),7.3-7.5(3H,m),7.6-7.9(8H,m),
8.01(2H,d,J=8.4Hz),8.12(1H,d,J=8.4Hz),8.31
(1H,d,J=7.7Hz),8.79(1H,d,J=7.0Hz),8.85(1H,
s)
FAB-MASS:m/z=1367(M+Na+)
元素分析 理论值C61H77N8O23NaS·6.5H2O:
C50.10,H6.20,N7.66
实验值:C50.09,H6.17,N7.62
实施例90
IR(KBr):3363,2937,2869,1646,1444,1255cm-1
NMR(DMSO-d6,δ):0.97(3H,d,J=6.7Hz),1.08(3H,d,
J=5.7Hz),1.2-1.6(10H,m),1.7-2.1(5H,m),2.1-
2.4(3H,m),2.5-2.7(1H,m),3.20(3H,s),3.2-3.4
(1H,m),3.6-4.6(16H,m),4.7-5.2(8H,m),5.16
(1H,d,J=3.1Hz),5.24(1H,d,J=4.5Hz),5.54(1H,
d,J=5.8Hz),6.73(1H,d,J=8.2Hz),6.8-7.0(2H,
m),7.1-7.4(6H,m),7.97(2H,d,J=8.8Hz),8.0-8.4
(6H,m),8.84(1H,s),8.92(1H,d,J=7.0Hz)
FAB-MASS:m/z=1403.6(M+Na+)
元素分析 理论值C59H77N10O23NaS2·6H2O:
C47.58,H6.02,N9.40
实验值:C47.72,H6.12,N9.42
实施例91
IR(KBr):3350,1668,1654,1625,1537,1521,1245,
1047cm-1
NMR(DMSO-d6,δ):0.9-1.1(6H,m),1.07(3H,d,
J=5.7Hz),1.4-2.0(7H,m),2.2-2.5(3H,m),2.5-2.6
(1H,m),3.1-3.3(1H,m),3.6-4.5(16H,m),4.7-5.1
(7H,m),5.09(1H,d,J=5.6Hz),5.16(1H,d,
J=3.1Hz),5.25(1H,d,J=4.4Hz),5.53(1H,d,
J=6.0Hz),6.73(1H,d,J=8.4Hz),6.8-7.2(6H,m)
7.2-7.5(4H,m),7.5-7.8(6H,m),8.11(1H,d,
J=8.4Hz),8.32(1H,d,J=7.7Hz),8.54(1H,d,
J=7.0Hz),8.84(1H,s)
FAB-MASS:m/z=1259(M+Na+)
元素分析 理论值C54H69N8O22NaS·8H2O:
C46.95,H6.20,N8.11
实验值:C47.20,H6.23,N8.28
实施例92
IR(KBr):3359,2929,2852,1668,1650,1631,1538,
1515cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.7Hz),1.09(3H,d,
J=6.1Hz),1.2-1.6(5H,m),1.6-2.5(10H,m),2.5-
2.6(1H,m),3.18(1H,m),3.7-4.5(15H,m),4.8-
5.2(8H,m),5.17(1H,d,J=3.1Hz),5.26(1H,d,
J=4.5Hz),5.55(1H,d,J=5.9Hz),6.73(1H,d,
J=8.1Hz),6.81(1H,s),6.85(1H,s),7.05(1H,s),
7.2-7.4(3H,m),7.45(2H,d,J=8.2Hz),7.96(2H,
d,J=8.2Hz),8.0-8.2(4H,s),8.2-8.3(1H,m),8.85
(1H,s),8.9-9.0(1H,d,J=7.0Hz)
FAB-MASS:m/z=1327.5(M+Na)+
元素分析 理论值C56H69N10O21S2Na·6H2O:
C47.59,H5.78,N9.91
实验值:C47.89,H5.76,N9.93
实施例93
IR(KBr):3350,1654,1629,1517,1249,1047cm-1
NMR(DMSO-d6,δ):0.9-1.1(6H,m),1.11(3H,d,
J=5.9Hz),1.6-2.0(5H,5),2.1-2.4(3H,s),2.6-2.7
(1H,m),3.1-3.3(1H,m),3.6-4.5(16H,m),4.7-5.2
(7H,m),5.10(1H,d,J=5.6Hz),5.17(1H,d,
J=3.1Hz),5.25(1H,d,J=4.5Hz),5.55(1H,d,
J=5.7Hz),6.7-6.9(3H,m),7.0-7.5(6H,m),7.74
(2H,d,J=8.8Hz),7.91(2H,d,J=8.5Hz),8.1-8.4
(8H,m),8.84(1H,s),8.97(1H,d,J=7.0Hz)
FAB-MASS:m/z=1363.5(M+Na)+
元素分析 理论值C59H69N10O23SNa·5H2O:
C49.51,H5.56,N9.79
实验值:C49.39,H5.63,N9.77
实施例94
IR(KBr):3355,2929,2856,1664,1631,1519,1440,
1282cm-1
NMR(DMSO-d6,δ):0.84(3H,t,J=6.7Hz),0.96(3H,d,
J=6.7Hz),1.07(3H,t,J=5.8Hz),1.2-1.5(12H,m),
1.7-2.0(5H,m),2.2-2.4(3H,m),2.5-2.7(1H,m),
2.94(2H,t,J=7.4Hz),3.1-3.3(1H,m),3.6-4.6
(14H,m),4.8-5.2(7H,m),5.10(1H,d,J=3.6Hz),
5.17(1H,d,J=3.1Hz),5.26(1H,d,J=4.5Hz),5.55
(1H,d,J=5.9Hz),6.73(1H,d,J=8.2Hz),6.8-7.0
(2H,m),7.0-7.5(4H,m),8.0-8.2(5H,m),8.27
(1H,d,J=7.7Hz),8.85(1H,s),8.93(1H,d,
J=7.0Hz)
FAB-MASS:m/z=1279(M+Na+)
元素分析 理论值C53H73N10OSNa·5.5H2O:
C46.93,H6.24,N10.33
实验值:C46.93,H6.46,N10.31
实施例95
IR(KBr):3363,1673,1648,1538,1253cm-1
NMR(DMSO-d6,δ):0.92(3H,t,J=6.8Hz),0.97(3H,d,
J=6.8Hz),1.10(3H,d,J=5.8Hz),1.2-1.5(6H,m),
1.7-2.1(5H,m),2.1-2.4(3H,m),2.5-2.6(1H,m),
3.1-3.3(1H,m),3.6-4.5(16H,m),4.7-5.1(9H,m),
5.16(1H,d,J=3.1Hz),5.24(1H,d,J=4.5Hz),5.54
(1H,d,J=5.8Hz),6.73(1H,d,J=8.2Hz),6.8-7.4
(8H,m),8.04(2H,d,J=8.8Hz),8.13(2H,d,
J=8.6Hz),8.2-8.4(4H,m),8.84(1H,s),8.98(1H,
d,J=7.0Hz)
FAB-MASS:m/z=1329.6(M+Na)+
元素分析 理论值C56H71N10O23SNa·7H2O:
C46.92,H5.97,N9.77
实验值:C46.86,H5.99,N9.77
实施例96
IR(KBr):3355,2929,1666,1648,1631,1515,1442,
1047cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.7Hz),0.97(3H,d,
J=6.7Hz),1.10(3H,d,J=5.8Hz),1.2-1.5(10H,m),
1.7-2.1(5H,m),2.1-2.4(3H,m),2.5-2.6(1H,m),
3.1-3.3(1H,m),3.6-4.6(16H,m),4.79(2H,d,
J=5.9Hz),4.8-5.2(5H,m),5.09(1H,d,J=5.5Hz),
5.16(1H,d,J=3.1Hz),5.23(1H,d,J=4.5Hz),5.53
(1H,d,J=5.9Hz),6.73(1H,d,J=8.0Hz),6.8-6.9
(2H,m),7.0-7.5(6H,m),7.97(2H,d,J=8.8Hz),
8.0-8.3(6H,m),8.83(1H,s),8.88(1H,d,
J=7.0Hz)
FAB-MASS:m/z=1373.5(M+Na)+
元素分析 理论值C58H75N10O22S2Na·6H2O:
C47.73,H6.01,N9.60
实验值:C47.57,H5.92,N9.53
实施例97
IR(KBr):3361,2925,2852,1668,1650,1631,1538,
1452,1049cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.9Hz),0.96(3H,d,
J=6.7Hz),1.08(3H,d,J=5.7Hz),1.2-1.4(11H,m),
1.4-1.6(2H,m),1.7-2.1(5H,m),2.1-2.5(5H,m),
2.5-2.6(1H,m),3.1-3.3(2H,m),3.7-4.5(14H,m),
4.7-5.0(7H,m),5.09(1H,d,J=5.6Hz),5.16(1H,
d,J=3.1Hz),5.25(1H,d,J=4.5Hz),5.54(1H,d,
J=5.8Hz),6.73(1H,d,J=8.2Hz),6.8-7.0(2H,d),
7.04(1H,s),7.2-7.5(3H,m),8.03(4H,s),8.0-
8.3(2H,m),8.84(1H,s),8.95(1H,d,J=7.0Hz)
FAB-MASS:m/z=1321.9(M+Na)+
元素分析 理论值C55H75N10O21S2Na·5H2O:
C47.54,H6.17,N10.08
实验值:C47.38,H6.12,N9.98
实施例98
IR(KBr):3374,2937,2875,1658,1629,1531,1436,
1255,1047cm-1
NMR(DMSO-d6,δ):0.9-1.11(6H,m),1.09(3H,d,
J=5.7Hz),1.2-1.5(4H,m),1.7-2.1(5H,m),2.2-2.5
(3H,m),2.6-2.7(1H,m),3.2-3.3(1H,m),3.6-4.5
(16H,m),4.80(2H,d,J=5.8Hz),4.8-5.2(5H,m),
5.10(1H,d,J=5.5Hz),5.17(1H,d,J=3.0Hz),5.24
(1H,d,J=4.5Hz),5.53(1H,d,J=5.8Hz),6.73(1H,
d,J=8.2Hz),6.8-7.0(2H,m),7.06(1H,s),7.10
(2H,d,J=8.9Hz),7.2-7.5(3H,m),7.68(1H,s),
7.86(2H,d,J=8.8Hz),8.0-8.4(6H,m),8.84(1H,
s),8.90(1H,d,J=7.0Hz)
FAB-MASS:m/z=1314(M+Na+)
元素分析 理论值C56H70N9O23NaS·6H2O:
C48.03,H5.90,N9.00
实验值:C47.92,H5.83,N8.88
实施例99
IR(KBr):3345,1646,1633,1531,1257cm-1
NMR(DMSO-d6,δ):0.97(3H,d,J=6.7Hz),1.11(3H,d,
J=5.7Hz),1.2-1.6(10H,m),1.7-2.5(8H,m),2.6-
2.7(1H,m),3.21(3H,s),3.3-3.4(1H,m),3.7-4.6
(16H,m),4.8-5.2(8H,m),5.16(1H,d,J=3.1Hz),
5.24(1H,d,J=4.5Hz),5.55(1H,d,J=5.7Hz),6.7-
6.9(3H,m),7.0-7.5(6H,m),8.0-8.3(8H,m),8.84
(1H,s),8.96(1H,d,J=7.0Hz)
FAB-MASS:m/z=1387.7(M+Na+)
元素分析 理论值C59H77N10O24NaS·6H2O:
C48.09,H6.09,N9.51
实验值:C47.81,H5.83,N9.38
实施例100
IR(KBr):3357,1668,1631,1429,1284,1047cm-1
NMR(DMSO-d6,δ):0.97(3H,d,J=6.7Hz),1.09(3H,d,
J=5.8Hz),1.8-2.4(6H,m),2.5-2.6(1H,m),3.1-3.2
(1H,m),3.7-4.6(14H,m),4.7-5.2(7H,m),5.10
(1H,d,J=5.5Hz),5.17(1H,d,J=3.1Hz),5.24(1H,
d,J=5.5Hz),5.53(1H,d,J=5.8Hz),6.75(1H,d,
J=8.2Hz),6.8-6.9(2H,m),7.05(1H,s),7.3-7.6
(9H,m),7.8-7.9(4H,m),8.0-8.2(5H,m),8.2-8.3
(1H,m),8.34(1H,d,J=9.3Hz),8.7-8.8(1H,m),
8.85(1H,s)
FAB-MASS:m/z=1332.7(M+Na+)
元素分析 理论值C58H65N10O22SNa·8H2O:
C47.93,H5.62,N9.64
实验值:C47.83,H5.53,N9.56
实施例101
IR(KBr):3353,2929,2856,1666,1631,1612,1496,
1440,1259cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.6Hz),0.97(3H,d,
J=6.5Hz),1.09(3H,d,J=5.9Hz),1.2-1.5(10H,m),
1.7-2.1(5H,m),2.2-2.5(3H,m),2.6-2.7(1H,m),
3.1-3.2(1H,m),3.6-4.5(16H,m),4.7-5.0(3H,m),
5.0-5.2(5H,m),5.10(1H,d,J=3.1Hz),5.26(1H,
d,J=4.2Hz),5.56(1H,d,J=5.5Hz),6.73(1H,d,
J=8.1Hz),6.8-7.0(2H,m),7.05(1H,s),7.1-7.5
(5H,m),8.0-84(8H,m),8.85(1H,s),8.95(1H,d,
J=7.0Hz)
FAB-MASS:m/z=1357.3(M+Na+)
元素分析 理论值C58H75N10O23NaS·7H2O:
C47.67,H6.14,N9.58
实验值:C47.63,H6.42,N9.52
实施例102
IR(KBr):3361,1670,1648,1633,1540,1519,
1249cm-1
NMR(DMSO-d6,δ):0.89(3H,t,J=7.0Hz),0.97(3H,d,
J=6.8Hz),1.10(3H,d,J=5.7Hz),1.2-1.5(6H,m),
1.6-2.4(8H,m),2.5-2.7(1H,m),3.1-3.3(1H,m),
3.6-4.5(16H,m),4.80(2H,d,J=5.8Hz),4.8-5.2
(5H,m),5.10(1H,d,J=5.4Hz),5.18(1H,d,
J=3.1Hz),5.25(1H,d,J=4.3Hz),5.55(1H,d,
J=5.7Hz),6.73(1H,d,J=8.2Hz),6.8-7.0(2H,m),
7.0-7.5(6H,m),8.02(1H,d,J=5.3Hz),8.0-8.4
(4H,m),8.42(2H,d,J=8.4Hz),8.48(2H,d,
J=8.9Hz),8.8-9.0(3H,m)
FAB-MASS:m/z=1339.3(M+Na+)
元素分析 理论值C58H73N10O22SNa·6H2O:
C48.87,H6.01,N9.83
实验值:C49.16,H5.92,N9.86
实施例103
IR(KBr):3350,2971,2859,1672,1629,1537,1442,
1247,1047cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.8Hz),1.0-1.2(6H,
m),1.2-1.6(12H,m),1.7-2.5(8H,m),2.5-2.6(1H,
m),3.2-3.6(7H,m),3.7-4.5(16H,m),4.76(2H,d,
J=5.6Hz),4.8-5.1(5H,m),5.09(1H,d,J=5.5Hz),
5.16(1H,d,J=3.1Hz),5.23(1H,d,J=5.5Hz),5.51
(1H,d,J=5.9Hz),6.73(1H,d,J=8.2Hz),6.8-6.9
(2H,m),7.0-7.1(3H,m),7.3-7.5(3H,m),7.67
(2H,d,J=6.9Hz),7.71(2H,d,J=6.9Hz),7.95(2H,
d,J=8.4Hz),8.05(1H,d,J=7.0Hz),8.23(1H,d,
J=7.7Hz),8.70(1H,d,J=7.0Hz),8.84(1H,s)
FAB-MASS:m/z=1377.1(M+Na+)
元素分析 理论值C60H83N8O24NaS·5H2O:
C49.86,H6.49,N7.75
实验值:C49.74,H6.73,N7.68
实施例104
IR(KBr):3349,2937,2858,1672,1629,1537,1444,
1249,1047cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.7Hz),1.08(3H,d,
J=5.6Hz),1.2-1.7(14H,m),1.7-2.1(5H,m),2.1-
2.4(5H,m),2.5-2.6(1H,m),3.1-3.2(1H,m),3.4-
3.6(4H,m),3.7-4.5(16H,m),4.77(2H,d,
J=5.7Hz),4.8-5.2(5H,m),5.09(1H,d,J=5.6Hz),
5.16(1H,d,J=3.1Hz),5.24(1H,d,J=4.5Hz),5.51
(1H,d,J=5.8Hz),6.73(1H,d,J=8.2Hz),6.8-6.9
(2H,m),7.0-7.1(3H,m),7.3-7.5(3H,m),7.6-7.8
(4H,m),7.96(2H,d,J=8.4Hz),8.10(1H,d,
J=8.4Hz),8.24(1H,d,J=7.7Hz),8.71(1H,d,
J=7.0Hz),8.89(1H,s)
FAB-MASS:m/z=1386.5(M+Na+)
元素分析 理论值C61H82N9O23NaS·6H2O:
C49.76,H6.43,N8.56
实验值:C49.99,H6.39,N8.52
实施例105
IR(KBr):3350,2933,2856,1664,1631,1604,1511,
1450,1243,1045cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.7Hz),0.96(3H,d,
J=6.5Hz),1.05(3H,d,J=5.7Hz),1.2-1.5(8H,m),
1.6-2.0(5H,m),2.1-2.4(3H,m),2.5-2.6(1H,m),
3.0-3.3(5H,m),3.6-4.4(20H,m),4.7-5.1(7H,m),
5.10(1H,d,J=5.5Hz),5.16(1H,d,J=3.1Hz),5.27
(1H,d,J=4.5Hz),5.51(1H,d,J=6.0Hz),6.7-7.1
(9H,m),7.2-7.5(3H,m),8.0-8.2(2H,m),8.2-8.4
(1H,m),8.4-8.6(1H,m),8.66(1H,d,J=2.2Hz),
8.85(1H,s)
FAB-MASS:m/z=1360(M+Na+)
元素分析 理论值C58H80N11O22SNa·6H2O:
C48.16,H6.41,N10.65
实验值:C47.91,H6.31,N10.56
实施例106
IR(KBr):3369,3345,2935,1672,1629,1511,1245,
1047cm-1
NMR(DMSO-d6,δ):0.96(3H,d,J=6.7Hz),1.06(3H,d,
J=5.8Hz),1.3-1.6(10H,m),1.6-2.0(5H,m),2.1-
2.4(3H,m),2.5-2.6(1H,m),3.20(3H,s),3.28
(2H,t,J=6.4Hz),3.1-3.4(5H,m),3.7-4.5(20H,
m),4.7-5.1(7H,m),5.08(1H,d,J=5.5Hz),5.15
(1H,d,J=3.1Hz),5.23(1H,d,J=4.5Hz),5.48(1H,
d,J=5.8Hz),6.73(1H,d,J=8.2Hz),6.82(2H,d,
J=9.1Hz),6.94(2H,d,J=9.1Hz),6.9-7.0(1H,m),
7.04(1H,s),7.3-7.5(3H,m),8.0-8.1(2H,m),
8.27(1H,d,J=7.7Hz),8.49(1H,d,J=7.0Hz),8.66
(1H,d,J=2.2Hz),8.84(1H,s)
FAB-MASS:m/z=1404(M+Na+)
实施例107
IR(KBr):3357,1847,1631,1537,1444,1249,
1049cm-1
NMR(DMSO-d6,δ):0.9-1.1(6H,m),1.09(3H,d,
J=5.9Hz),1.6-2.4(8H,m),2.4-2.5(1H,m),3.1-3.3
(1H,m),3.6-4.5(16H,m),4.8-5.2(7H,m),5.10
(1H,d,J=5.6Hz),5.17(1H,d,J=3.1Hz),5.25(1H,
d,J=4.5Hz),5.55(1H,d,J=5.9Hz),6.73(1H,d,
J=8.2Hz),6.8-7.0(2H,m),7.0-7.6(6H,m),7.73
(2H,d,J=8.7Hz),7.86(2H,d,J=8.5Hz),8.0-8.3
(8H,m),8.84(1H,s),8.9-9.0(1H,m)
FAB-MASS:m/z=1379.4(M+Na)+
元素分析 理论值C59H69N10O22S2Na·6H2O:
C48.36,H5.57,N9.56
实验值:C48.18,H5.60,N9.36
目标化合物(108)至(117)按照与实施例27相似的方式得到。
实施例108
IR(KBr):3350,2933,1670,1627,1521,1436,1272,
1047cm-1
NMR(DMSO-d6,δ):0.85(3H,t,J=6.7Hz),0.92(3H,d,
J=6.7Hz),1.1-1.4(11H,m),1.7-2.4(9H,m),3.1-
3.2(1H,m),3.5-5.4(27H,m),6.6-7.2(8H,m),
7.5-7.8(3H,m),7.8-8.0(3H,m),8.1-8.8(3H,m)
FAB-MASS:m/z=1249.4(M+Na+)
元素分析 理论值C52H71N10O21NaS·7H2O:
C46.15,H6.33,N10.35
实验值:C46.12,H6.35,N10.24
实施例109
IR(Kbr pelet):3361,2933,2856,1670,1652,1616,
1540,1508,1448,1261,1047cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.6Hz),0.97(3H,d,
J=6.8Hz),1.12(3H,d,J=6.8Hz),1.2-1.5(10H,m),
1.7-2.0(5H,m),2.2-2.6(4H,m),3.1-3.2(1H,m),
3.7-4.4(16H,m),4.8-5.3(10H,m),5.59(1H,d,
J=6.0Hz),6.7-6.9(3H,m),7.0-7.4(7H,m),7.8-8.2
(4H,m),8.8-9.0(2H,m)
FAB-MASS:m/z=1280.3(M+Na+)
元素分析 理论值C54H72N9O23NaS·7H2O:
C46.45,H6.21,N9.03
实验值:C46.68,H6.44,N9.03
实施例110
IR(KBr):3350,2931,1670,1627,1540,1436,1276,
1047cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=6.8Hz),0.93(2H,d,
J=8.8Hz),1.08(2H,d,J=5.9Hz),1.2-1.4(4H,m),
1.5-1.7(2H,m),1.7-2.1(3H,m),2.1-2.4(3H,m),
2.6-2.7(3H,m),3.1-3.3(1H,m),3.6-4.5(17H,m),
4.7-5.4(8H,m),6.73(1H,d,J=8.2Hz),6.83(2H,
d,J=8.2Hz),7.0-7.1(1H,m),7.2-7.5(5H,m),7.65
(2H,d,J=8.2Hz),7.74(2H,d,J=8.4Hz),7.98(2H,
d,J=8.4Hz),8.08(1H,d,J=8.5Hz),8.25(1H,d,
J=8.5Hz),8.74(1H,d,J=7.6Hz),8.7-9.0(1H,br)
FAB-MASS:m/z=1231.2(M+Na+)
元素分析 理论值C53H69N8O21NaS·3H2O:
C50.39,H5.98,N8.87
实验值:C50.34,H6.25,N8.90
实施例111
IR(KBr):3353.6,1670.1,1652.7,1623.8cmU
NMR(DMSO-d6,δ):0.96(3H,d,J=6.7Hz),1.07(3H,d,
J=5.6Hz),1.20-1.62(8H,m),1.62-2.00(5H,m),
2.10-2.65(4H,m),3.20(3H,s),3.08-3.40(1H, m),
3.30(2H,t,J=6.5Hz),3.53-4.50(15H,m),4.68-
5.13(9H,m),5.16(1H,d,J=2.9Hz),5.26(1H,d,
J=4.5Hz),5.53(1H,d,J=5.9Hz),6.68-6.95(4H,m),
6.95-7.11(3H,m),7.20-7.52(3H,m),7.55-7.95
(7H,m),8.13(1H,d,J=8.4Hz),8.31(1H,d,
J=7.7Hz),8.53(1H,d,J=7.0Hz),8.85(1H,s)
FAB-MASS:m/z=1331.5(M+Na-1)
元素分析 理论值C58H77N8NaO23S·6H2O:
C49.15,H6.33,N7.91
实验值:C49.07,H6.53,N7.84
实施例112
IR(KBr):3350,2937,1673,164 6,1631,1538,1519,
1456,1247,1049cm-1
NMR(DMSO-d6,δ):0.97(3H,d,J=6.6Hz),1.07(3H,d,
J=5.7Hz),1.3-2.4(25H,m),2.5-2.6(1H,m),3.2-
3.4(1H,m),3.5-4.6(20H,m),4.8-5.7(11H,m),
6.73(1H,d,J=8.0Hz),6.9-7.0(2H,m),7.0-7.2
(3H,m),7.3-7.6(3H,m),7.74(2H,d,J=8.5Hz),
7.77(2H,d,J=8.3Hz),8.02(2H,d,J=8.3Hz),8.13
(1H,d,J=8.4Hz),8.30(1H,d,J=7.7Hz),8.77(1H,
d,J=7.0Hz),8.85(1H,s)
FAB-MASS:m/z=1389(M+Na+)
元素分析 理论值C61H83N8O24NaS·7H2O:
C49.06,H6.55,N7.50
实验值:C49.03,H6.54,N7.56
实施例113
NMR(DMSO-d6,δ):0.84(3H,t,J=6.7Hz),0.96(3H,d,
J=6.7Hz),1.07(3H,d,J=5.9Hz),1.1-1.3(14H,m),
1.7-2.1(5H,m),2.2-2.5(3H,m),2.6-2.7(1H,m),
3.1-3.3(1H,m),3.7-4.5(16H,m),4.7-5.1(7H,m),
5.10(1H,d,J=5.5Hz),5.16(1H,d,J=3.1Hz),5.25
(1H,d,J=4.5Hz),5.49(1H,d,J=5.7Hz),6.53(1H,
d,J=3.1Hz),6.73(1H,d,J=8.2Hz),6.8-6.9(2H,
m),7.05(1H,m),7.31(1H,d,J=8.1Hz),7.4-7.6
(4H,m),7.70(1H,d,J=6.7Hz),8.08(1H,d,
J=8.4Hz),8.18(1H,s),8.31(1H,d,J=7.7Hz),8.57
(1H,d,J=7.0Hz),8.85(1H,s)
FAB-MASS:m/z=1264(M+Na+)
元素分析 理论值C54H76N9O21NaS·6H2O:
C48.03,H6.57,N9.34
实验值:C48.02,H6.61,N9.28
实施例114
IR(KBr):3350,2937,1668,1631,1537,1247,1047cm-1
NMR(DMsO-d6,δ):0.85(3H,t,J=7.4Hz),0.96(3H,d,
J=6.5Hz),1.07(3H,d,J=5.7Hz),1.3-1.7(7H,m),
1.7-2.1(5H,m),2.2-2.4(3H,m),2.6-2.7(1H,m),
3.0-3.8(1 6H,m),3.8-4.6(11H,m),4.7-5.3(6H,
m),6.73(1H,d,J=8.2Hz),6.8-7.0(2H,m),7.0-7.2
(3H,m),7.3-7.5(3H,m),7.6-7.8(4H,m),7.96
(2H,d,J=8.3Hz),8.11(1H,d,J=8.2Hz),8.26(1H,
d,J=7.6Hz),8.6-9.0(2H,m)
FAB-MASS:m/z=1319.4(M+Na+)
元素分析 理论值C57H77N8O23NaS·8H2O:
C47.50,H6.50,N7.77
实验值:C47.72,H6.85,N7.85
实施例115
IR(KBr):3350,1666,1631,1546,1276,1247cm-1
NMR(DMSO-d6,δ):0.97(3H,d,J=7.5Hz),1.08(3H,d,
J=5.7Hz),1.4-1.6(4H,m),1.6-2.1(5H,m),2.1-2.4
(3H,m),2.5-2.6(1H,m),3.1-3.3(1H,m),3.23
(3H,s),3.3-3.5(2H,m),3.7-4.5(16H,m),4.79
(2H,d,J=6.2Hz),4.8-5.1(5H,m),5.11(1H,d,
J=5.6Hz),5.18(1H,d,J=3.1Hz),5.26(1H,d,
J=4.4Hz),5.54(1H,d,J=5.7Hz),6.73(1H,d,
J=8.1Hz),6.8-7.0(2H,m),7.0-7.1(3H,m),7.3-7.5
(3H,m),7.6-7.9(8H,m),8.01(2H,d,J=8.4Hz),
8.08(1H,d,J=8.4Hz),8.32(1H,d,J=7.7Hz),8.80
(1H,d,J=7.0Hz),8.85(1H,s)
FAB-MASS:m/z=1353.9(M+Na+)
元素分析 理论值C60H75N8O23NaS·9.5H2O:
C47.96,H6.31,N7.46
实验值:C47.97,H6.25,N7.41
实施例116
IR(KBr):3450,2935,1675,1650,1540,1513,1454,
1047cm-1
NMR(DMSO-d6,δ):0.97(3H,d,J=6.7Hz),1.09(3H,d,
J=5.9Hz),1.60(6H,s),1.7-2.4(6H,m),2.5-2.6
(1H,m),3.1-3.6(5H,m ),3.7-4.5(14H,m),4.7-5.0
(3H,m),5.0-5.2(4H,m),5.11(1H,d,J=5.5Hz),
5.18(1H,d,J=3.1Hz),5.26(1H,d,J=4.5Hz),5.56
(1H,d,J=6.0Hz),6.8-7.5(9H,m),7.84(2H,d,
J=8.8Hz),8.0-8.4(6H,m),8.85(1H,s),8.91(1H,
d,J=7.0Hz)
FAB-MASS:m/z=1328(M+Na)+
元素分析 理论值C55H68N11O21S2Na·8H2O:
C45.55,H5.84,N10.62
实验值:C45.62,H5.70,N10.54
实施例117
IR(KBr):3350,2939,1664,1627,1531,1446,1249,
1049cm-1
NMR(DMSO-d6,δ):0.8-1.0(6H,m),1.4-1.9(9H,m),
2.0-2.5(4H,m),3.1-3.2(1H,m),3.22(3H,s),
3.3-3.4(2H,m),3.51(2H,s),3.6-4.4(16H,m),
4.7-5.2(7H,m),5.07(1H,d,J=5.6Hz),5.17(1H,
d,J=3.1Hz),5.23(1H,d,J=4.5Hz),5.54(1H,d,
J=5.9Hz),6.7-6.8(3H,m),7.0-7.4(8H,m),7.5-7.7
(4H,m),7.70(4H,s),8.1-8.2(2H,m),8.51(1H,
d,J=7.0Hz),8.83(1H,s)
FAB-MASS:m/z=1367.6(M+Na+)
元素分析 理论值C61H77N8O23SNa·6.5H2O:
C50.01,H6.20,N7.66
实验值:C50.30,H6.50,N7.75
实施例118
向目标化合物(61)(0.25g)在甲醇(50ml)中的溶液里加入干燥的10%钯/碳(0.2g),在氢气氛下搅拌6小时,滤除钯/碳,将滤液减压蒸发,得到目标化合物118(179mg)。
IR(KBr):3400,1668.1,1627.6cm-1
NMR(DMSO-d6,δ):0.92(3H,d,J=6.7Hz),1.1-2.45
(40H,m),3.20(3H,s),3.28(2H,t,J=6.5Hz),3.0-
3.4(1H,m),3.5-4.7(14H,m),4.95-5.5(12H,m),
6.55(1H,d,J=8.4Hz),6.84(1H,s),6.86(1H,d,
J=8.4Hz),7.0-7.3(4H,m),7.9-8.3(4H,m)
FAB-MASS:m/z=1292(M+Na)
元素分析 理论值C54H88N9O22SNa·5H2O:
C47.67,H7.26,N9.26
实验值:C47.72,H7.35,N8.95
目标化合物(119)至(121)按照与实施例118相似的方式得到。
实施例119
NMR(DMSO-d6,δ):0.87(3H,t,J=6.6Hz),1.00(3H,d,
J=7.3Hz),1.03(3H,d,J=6.0Hz),1.2-1.5(4H,m),
1.5-2.0(5H,m),2.1-2.7(8H,m),3.17(1H,m),
3.6-4.5(14H,m),4.65-5.7(12H,m),6.72(1H,d,
J=8.1Hz),6.75(1H,s),6.80(1H,d,J=8.1Hz),7.05
(1H,s),7.1-7.7(15H,m),8.0-8.6(4H,m),8.85
(1H,s)
FAB-MASS:m/z=1274(M+Na)
元素分析 理论值C55H74N9O21SNa·7H2O:
C47.93,N6.43,N9.15
实验值:C48.12,N6.56,N9.03
实施例120
IR(KBr):3355.5,1672.01629.6cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.6Hz),0.98(3H,d,
J=6.5Hz),1.03(3H,d,J=6.0Hz),1.2-2.6(21H,m),
3.18(1H,m),3.6-4.5(16H,m),4.65-5.55(12H,m),
6.6-7.5(10H,m),8.0-8.6(4H,m),8.89(1H,s)
FAB-MASS:m/z=1256(M+Na)
实施例121
IR(KBr):3357.5,1660.4,1629.6,1249.6cm-1
NMR(DMSO-d6,δ):0.86(3H,t,J=6.6Hz),0.96(3H,d,
J=6.8Hz),1.03(3H,d,J=6.0Hz),1.1-1.5(12H,m),
1.6-2.0(5H,m),2.0-2.5(4H,m),3.07(1H,m),
3.5-4.5(16H,m),4.6-5.6(12H,m),6.72(1H,d,
J=8.1Hz),6.7-6.9(4H,m),7.04(1H,s),7.16(1H,
s),7.1-7.5(2H,m),7.25(2H,d,J=8.6Hz),8.0-8.2
(3H,m),8.46(1H,d,J=7Hz),8.84(1H,s)
FAB-MASS:m/z=1256(M+Na)
元素分析 理论值C52H76N9O22SNa·7H2O:
C45.91,H6.67,N9.27
实验值:C45.98,H6.67,N9.10
实施例122
将目标化合物(11)(795mg)在水(16ml)中的溶液放置240小时。在ODS(YMC-凝胶ODS-AMS 50)上对溶液进行柱色谱,用25%的CH3CN/H2O洗脱。将含有目标化合物的级分合并,减压去除乙腈。残余物冷冻干燥,得到目标化合物(123)(38mg)。
IR(KBr):3361,2956,2875,1668,1627,1521,1249,
1047cm-1
NMR(DMSO-d6,δ):0.8-1.5(19H,m),1.6-2.4(13H,m),
3.1-3.2(1H,m),3.5-4.1(12H,m),4.1-4.7(10H,
m),4.9-5.6(5H,m),5.98(1H,d,J=10.6Hz),6.36
(1H,d,J=10.6Hz),6.7-7.3(12H,m),7.4-8.0(7H,
m)
FAB-MASS:m/z=1273.1(M+Na+)
元素分析 理论值C55H71N8O22NaS·11H2O:
C45.58,H6.47,N7.73
实验值:C45.83,H6.26,N7.75
目标化合物(123)按照与实施例118相似的方式得到。
实施例123
IR(KBr):3349.7,1670.1,1627.6cm-1
NMR(DMSO-d6,δ):0.87(3H,t,J=7.2Hz),0.96(3H,d,
J=6.7Hz),1.13(3H,d,J=5.7Hz),1.18-1.55(10H,
m),1.58-2.08(5H,m),2.08-2.90(4H,m),2.90-3.30
(2H,m),3.60-4.50(17H,m),4.70-5.70(12H,m),
6.65-7.60(11H,m),7.80(2H,br s),7.95-8.23(2H,
m),8.75(1H,d,J=7.0Hz),8.85(1H,s)
FAB-MASS:m/z=1114.4(M-SO4-2)
元素分析 理论值C52H77N9O21S·6H2O:
C47.88,H6.88,N9.66
实验值:C47.60,H6.74,N9.53
以下化合物(124)按照与实施例1相似的方式得到。
实施例124
IR(KBr):3324,2937,2873,1664,1629,1442,
1257cm-1
NMR(DMSO-d6,δ):0.91(3H,t,J=7.1Hz),0.96(3H,d,
J=6.7Hz),1.09(3H,d,J=5.7Hz),1.3-1.5(4H,m),
1.7-2.6(9H,m),3.1-3.3(1H,m),3.7-4.6(16H,m),
4.7-5.1(7H,m),5.11(1H,d,J=5.6Hz),5.17(1H,
d,J=3.1Hz),5.26(1H,d,J=4.5Hz),5.55(1H,d,
J=5.8Hz),6.7-6.9(3H,m),7.0-7.6(6H,m),7.97
(2H,d,J=8.8Hz),8.0-8.4(6H,m),8.85(1H,s),
8.92(1H,d,J=7.0Hz)
FAB-MASS:m/z=1331(M+Na+)
元素分析 理论值C55H69N10O22NaS2:
C45.45,H5.89,N9.64
实验值:C45.71,H5.68,N9.60
Claims (6)
1、一种具有以下通式的多肽化合物或其可药用的盐:
其中R1是:
被苯基取代的哌嗪基取代的苯甲酰基,所述苯基被C1-C6烷氧基取代;
被苯基取代的异噁唑基取代的苯甲酰基,所述苯基被C1-C6烷氧基取代;
被苯基取代的噻二唑基取代的苯甲酰基,所述苯基被C1-C6烷氧基(C7-C20)烷氧基取代;或是
被苯基取代的噁二唑基取代的苯甲酰基,所述苯基被C1-C6烷氧基取代。
2、权利要求1的化合物,其中
R1是被由苯基取代的异噁唑基取代的苯甲酰基,其中苯基被戊氧基取代。
3、权利要求2的化合物,其中
R1是4-[5-(4-戊氧基苯基)异噁唑-3-基]苯甲酰基。
5、一种药物组合物,其中包括作为活性成分的一种权利要求1的化合物或其可药用盐以及与其混合的可药用的载体或赋形剂。
6、权利要求1的化合物或其可药用的盐在制造用于治疗或预防感染性疾病的药物中的用途。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9420425A GB9420425D0 (en) | 1994-10-07 | 1994-10-07 | New compound |
GB9508745.8 | 1995-04-28 | ||
GBGB9508745.8A GB9508745D0 (en) | 1995-04-28 | 1995-04-28 | New compound |
GB9420425.2 | 1995-04-28 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1168675A CN1168675A (zh) | 1997-12-24 |
CN1203089C true CN1203089C (zh) | 2005-05-25 |
Family
ID=26305774
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Application Number | Title | Priority Date | Filing Date |
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CNB95196643XA Expired - Lifetime CN1203089C (zh) | 1994-10-07 | 1995-09-29 | 新化合物 |
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US (2) | US6107458A (zh) |
EP (1) | EP0788511B1 (zh) |
JP (2) | JP2897427B2 (zh) |
KR (1) | KR100353303B1 (zh) |
CN (1) | CN1203089C (zh) |
AR (1) | AR041770A1 (zh) |
AT (1) | ATE229541T1 (zh) |
AU (1) | AU696949B2 (zh) |
BR (2) | BR9504791B1 (zh) |
CA (1) | CA2202058C (zh) |
DE (2) | DE122008000025I2 (zh) |
DK (1) | DK0788511T3 (zh) |
ES (1) | ES2187575T3 (zh) |
FI (1) | FI119988B (zh) |
FR (1) | FR08C0028I2 (zh) |
HK (1) | HK1004136A1 (zh) |
HU (1) | HU228151B1 (zh) |
IL (1) | IL115484A (zh) |
LU (1) | LU91452I2 (zh) |
MX (1) | MX9702531A (zh) |
NL (1) | NL300352I2 (zh) |
NO (2) | NO328483B1 (zh) |
OA (1) | OA10475A (zh) |
PT (1) | PT788511E (zh) |
RU (1) | RU2165423C2 (zh) |
TR (1) | TR199501229A2 (zh) |
WO (1) | WO1996011210A1 (zh) |
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