JP2000512642A - テトラアザマクロ環の製造方法 - Google Patents
テトラアザマクロ環の製造方法Info
- Publication number
- JP2000512642A JP2000512642A JP10502194A JP50219498A JP2000512642A JP 2000512642 A JP2000512642 A JP 2000512642A JP 10502194 A JP10502194 A JP 10502194A JP 50219498 A JP50219498 A JP 50219498A JP 2000512642 A JP2000512642 A JP 2000512642A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- mol
- solution
- scheme
- 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.)
- Granted
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 17
- 150000002678 macrocyclic compounds Chemical class 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 73
- 238000000034 method Methods 0.000 claims abstract description 37
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 36
- 230000003647 oxidation Effects 0.000 claims abstract description 23
- 239000007864 aqueous solution Substances 0.000 claims abstract description 18
- 239000007800 oxidant agent Substances 0.000 claims abstract description 17
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical class O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000000203 mixture Substances 0.000 claims abstract description 9
- 230000002378 acidificating effect Effects 0.000 claims abstract description 7
- 239000002168 alkylating agent Substances 0.000 claims abstract description 7
- 229940100198 alkylating agent Drugs 0.000 claims abstract description 7
- 229920000768 polyamine Polymers 0.000 claims abstract description 6
- 238000006482 condensation reaction Methods 0.000 claims abstract description 4
- 230000005494 condensation Effects 0.000 claims abstract 3
- 238000009833 condensation Methods 0.000 claims abstract 3
- 239000000243 solution Substances 0.000 claims description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 31
- QBPPRVHXOZRESW-UHFFFAOYSA-N 1,4,7,10-tetraazacyclododecane Chemical compound C1CNCCNCCNCCN1 QBPPRVHXOZRESW-UHFFFAOYSA-N 0.000 claims description 24
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 15
- 229910052794 bromium Inorganic materials 0.000 claims description 15
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- 125000004054 acenaphthylenyl group Chemical group C1(=CC2=CC=CC3=CC=CC1=C23)* 0.000 claims description 13
- HXGDTGSAIMULJN-UHFFFAOYSA-N acetnaphthylene Natural products C1=CC(C=C2)=C3C2=CC=CC3=C1 HXGDTGSAIMULJN-UHFFFAOYSA-N 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 230000007062 hydrolysis Effects 0.000 claims description 9
- 238000006460 hydrolysis reaction Methods 0.000 claims description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- -1 alkaline earth metal carbonates Chemical class 0.000 claims description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 6
- 239000003929 acidic solution Substances 0.000 claims description 6
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 6
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 5
- 239000000920 calcium hydroxide Substances 0.000 claims description 5
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical group 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- NYYDZOSYLUOKEM-UHFFFAOYSA-N oxaldehyde;hydrate Chemical compound O.O=CC=O NYYDZOSYLUOKEM-UHFFFAOYSA-N 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- SRRKNRDXURUMPP-UHFFFAOYSA-N sodium disulfide Chemical compound [Na+].[Na+].[S-][S-] SRRKNRDXURUMPP-UHFFFAOYSA-N 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 claims description 3
- 239000005708 Sodium hypochlorite Substances 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 150000002978 peroxides Chemical class 0.000 claims description 3
- 239000012286 potassium permanganate Substances 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 3
- 239000003021 water soluble solvent Substances 0.000 claims description 3
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 239000003957 anion exchange resin Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000010828 elution Methods 0.000 claims description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 2
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 claims description 2
- 229910052723 transition metal Inorganic materials 0.000 claims description 2
- 150000003624 transition metals Chemical class 0.000 claims description 2
- XOPKWEWYQBTZSF-UHFFFAOYSA-N 1,2,5,9-tetrazacyclododecane Chemical compound N1CCNCCCNCCCN1 XOPKWEWYQBTZSF-UHFFFAOYSA-N 0.000 claims 1
- JMBIWKJKSNHIIC-UHFFFAOYSA-N 1,3,6,10-tetrazacyclododecane Chemical compound C1CNCCNCNCCNC1 JMBIWKJKSNHIIC-UHFFFAOYSA-N 0.000 claims 1
- 230000002152 alkylating effect Effects 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- 239000000047 product Substances 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 125000004957 naphthylene group Chemical group 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 5
- VILCJCGEZXAXTO-UHFFFAOYSA-N 2,2,2-tetramine Chemical compound NCCNCCNCCN VILCJCGEZXAXTO-UHFFFAOYSA-N 0.000 description 4
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 4
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 description 4
- 238000005903 acid hydrolysis reaction Methods 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 4
- 229940015043 glyoxal Drugs 0.000 description 4
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- ZAXCZCOUDLENMH-UHFFFAOYSA-N 3,3,3-tetramine Chemical compound NCCCNCCCNCCCN ZAXCZCOUDLENMH-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- UWMHHZFHBCYGCV-UHFFFAOYSA-N 2,3,2-tetramine Chemical compound NCCNCCCNCCN UWMHHZFHBCYGCV-UHFFFAOYSA-N 0.000 description 2
- ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 2
- RXFCIXRFAJRBSG-UHFFFAOYSA-N 3,2,3-tetramine Chemical compound NCCCNCCNCCCN RXFCIXRFAJRBSG-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229910052776 Thorium Inorganic materials 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 229920001429 chelating resin Polymers 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 239000013065 commercial product Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- RYHQMKVRYNEBNJ-BMWGJIJESA-K gadoterate meglumine Chemical compound [Gd+3].CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC(=O)CN1CCN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC1 RYHQMKVRYNEBNJ-BMWGJIJESA-K 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- XJFQPBHOGJVOHU-UHFFFAOYSA-N n'-[2-(2-aminoethylamino)ethyl]ethane-1,2-diamine;hydrate Chemical compound O.NCCNCCNCCN XJFQPBHOGJVOHU-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- SPXOTSHWBDUUMT-UHFFFAOYSA-M 4-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=C(S([O-])(=O)=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-M 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 150000000921 Gadolinium Chemical class 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 229910052689 Holmium Inorganic materials 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- KFAUAWMNLGGWLP-UHFFFAOYSA-N azacyclododecane Chemical compound C1CCCCCNCCCCC1 KFAUAWMNLGGWLP-UHFFFAOYSA-N 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 238000011095 buffer preparation Methods 0.000 description 1
- 239000004566 building material Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229910021485 fumed silica Inorganic materials 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 229910003480 inorganic solid Inorganic materials 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000004689 octahydrates Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- JBJWASZNUJCEKT-UHFFFAOYSA-M sodium;hydroxide;hydrate Chemical compound O.[OH-].[Na+] JBJWASZNUJCEKT-UHFFFAOYSA-M 0.000 description 1
- IXGNPUSUVRTQGW-UHFFFAOYSA-M sodium;perchlorate;hydrate Chemical compound O.[Na+].[O-]Cl(=O)(=O)=O IXGNPUSUVRTQGW-UHFFFAOYSA-M 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.一般式(I): (式中、n、p及びqは、独立してO又は1である) で示されるテトラアザマクロ環の製造方法であって、下記スキームの工程を含む 方法。 スキーム ここで、 工程a):水、水溶性の溶媒、又はそれらの混合物中で、化学量論量(2mol)の又 は少し過剰な水酸化カルシウムの存在下、0〜50℃で、式(III)のポリアミ ン類と、式(IV)のグリオキサール誘導体、〔式中、Yは−OH(グリオキサー ル水和物)又は(−SO3 -Na+)(Bertagnini塩)である〕とを縮合反応させて 、式(V)の化合物を得て; 工程b):アルカリ又はアルカリ土類金属炭酸塩から選ばれる塩基を、化合物( V)1molあたり少なくとも2molの存在下、式(V)の化合物と、アルキル化剤 :X−CH2−(CH2)q−CH2−X(式中、qは前記と同義であり、Xはハロ ゲン又はスルホン酸反応性誘導体)とを、少なくとも化学量論量で25〜150 ℃で縮合させて、式(II)の化合物を得て; 工程c):水、又は水と酸化に耐性な有機溶媒から構成される2相系中で、式( II)の化合物と酸化剤を、0〜100℃で酸化反応させて、酸化生成物の混合物 を得て、それを 工程d):2よりも低いpHの酸性水溶液、又は12より高いpHの塩基性水溶液中 で、110〜200℃で加水分解する。 2.工程c)で用いる酸化剤が、酸性溶液中の、高レベル酸化での遷移金属誘導 体類;陽性の酸化状態でのハロゲン誘導体類;ハロゲン類;過酸化物類;過酸化 酸塩;酸素からなる群から選ばれる、請求項1記載の方法。 3.工程c)で用いる酸化剤が、濃硫酸性溶液や二硫化ナトリウム中の、過マン ガン酸カリウム;次亜塩素酸ナトリウム;臭素及び塩素;過酸化水素;過硫酸ナ トリウム;酸素からなる群から選ばれる、請求項1記載の方法。 4.前記の酸化剤が、弱酸性溶液中の臭素である、請求項1記載の方法。 5.工程b)で用いるアルキル化剤が、1,2−ジブロモエタン及び1,2−ジ クロロエタンから選ばれる、請求項1記載の方法。 6.下記のスキームにしたがって: スキーム請求項1に記載の工程a)及びb)を含む、式(II)のテトラ環化合物を製造す る、請求項1記載の方法。 7.下記の化合物を製造する、請求項6記載の方法: 式(II)においてn、p及びqが0である2a,4a,6a,8a−デカヒド ロテトラアザシクロペンタ〔fg〕アセナフチレン; 式(II)においてnが1であり、p及びqの両方が0である7H−2a,4a ,6a,9a−デカヒドロ−テトラアザシクロヘプタ〔jklアシダセン; 式(II)においてnが0であり、pが1であり、qが0である1H,6H−3 a,5a,8a,10a−デカヒドロ−テトラアザピレン; 式(II)においてnが1であり、pが1であり、qが0である1H,6H,9 H−3a,5a,8a,11a−デカヒドロ−テトラアザシクロヘプタ〔def フェナントレン。 8.下記の化合物を製造する、請求項1〜7のいずれか1項記載の方法: 式(I)の化合物においてnが1であり、p及びqの両方が0である1,4, 7,10−テトラアザシクロドデカン; 式(I)の化合物においてnが0であり、pが1であり、qが0である1,4 ,8,11−テトラアザシクロドデカン; 式(I)の化合物においてnが1であり、pが1であり、qが0である1,4 ,8,12−テトラアザシクロドデカン。 9.下記のスキームにしたがって: スキーム 請求項1〜5に記載の工程a)、b)、c)及びd)により、式(VIII)の1, 4,7,10−テトラアザシクロドデカンを製造する、請求項1〜7のいずれか 1項記載の方法。 10.工程c)で用いる酸化剤が、pH4〜5の水溶液中、化合物(VII)1molあ たり臭素2〜3molの比率で、温度17〜30℃で用いる臭素である、請求項9 記載の方法。 11.臭素水溶液のpHが、4.5であり、化合物(VII)1molあたり臭素2.5m olの比率で添加する、請求項10記載の方法。 12.請求項1記載の式(II)の中間体に対応する、式(X)の化合物の製造方 法であって、nがqと同じである場合、下記のスキーム: スキーム工程a):請求項1記載の反応条件下に、式(VI)のポリアミン類と、式(IV) のグリオキサール誘導体、〔式中、Yは−OH(グリオキサール水和物)又は( −SO3 -Na+)(Bertagnini塩)である〕とを、2:1のモル比で縮合反応さ せて、式(XII)の化合物を得て; 工程b):請求項1記載の反応条件下に、アルキル化剤:X−CH2−(CH2)q −CH2-Xの少なくとも2molを、式(XII)の化合物と縮合させて、式(X) の化合物を得る方法。 13.式(X)の化合物において、n、p及びqが0である、2a,4a,6a ,8a−デカヒドロテトラアザシクロペンタ〔fg〕アセナフチレンを製造する 、請求項11記載の方法。 14.下記のスキームにしたがって、 スキーム 式(XIII)の中間体を形成する酸化工程を含む、請求項10記載の方法。 15.請求項14記載の方法での、式(XIII)の中間体。 16.酸化反応の末期の後に、過塩素酸塩を溶液に添加して、式(XIV):の化合物を得る、請求項14記載の化合物(XIV)の製造方法。 17.請求項14記載の方法により得ることができる、式(XIV)の化合物。 18.化合物(XV): で示される化合物の製造方法であって、陰イオン交換樹脂(Cl-形)カラム上 で、請求項15により調製した化合物(XIV)水溶液の溶離により、イソプロパ ノールから単離することができる、化合物(XV)を含有する溶液を得る方法。 19.請求項18記載の方法により得ることができる、式(XV)の化合物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT96A001257 | 1996-06-21 | ||
IT96MI001257A IT1284046B1 (it) | 1996-06-21 | 1996-06-21 | Processo per la preparazione di tetraazamacrocicli |
PCT/EP1997/002987 WO1997049691A1 (en) | 1996-06-21 | 1997-06-09 | A process for the preparation of tetraazamacrocycles |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2000512642A true JP2000512642A (ja) | 2000-09-26 |
JP4308323B2 JP4308323B2 (ja) | 2009-08-05 |
Family
ID=11374458
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP50219498A Expired - Lifetime JP4308323B2 (ja) | 1996-06-21 | 1997-06-09 | テトラアザマクロ環の製造方法 |
Country Status (16)
Country | Link |
---|---|
US (3) | US5880281A (ja) |
EP (1) | EP0914320B1 (ja) |
JP (1) | JP4308323B2 (ja) |
CN (1) | CN1083442C (ja) |
AT (1) | ATE223389T1 (ja) |
AU (1) | AU3256497A (ja) |
CA (1) | CA2258768C (ja) |
CZ (1) | CZ295406B6 (ja) |
DE (1) | DE69715211T2 (ja) |
ES (1) | ES2183185T3 (ja) |
HU (1) | HU223439B1 (ja) |
IN (1) | IN183348B (ja) |
IT (1) | IT1284046B1 (ja) |
NO (1) | NO310621B1 (ja) |
WO (1) | WO1997049691A1 (ja) |
ZA (1) | ZA975425B (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006527241A (ja) * | 2003-06-13 | 2006-11-30 | サントル ナシオナル ドゥ ラ ルシェルシェサイアンティフィク(セエヌエールエス) | シス−8b−メチルデカヒドロ−2a,4a,6a,8a−テトラアザシクロペンタ[fg]アセナフチレン、シス−デカヒドロ−2a,4a,6a,8a−テトラアザシクロペンタ[fg]アセナフチレン、サイクレンおよび官能化サイクレン |
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1284046B1 (it) * | 1996-06-21 | 1998-05-08 | Bracco Spa | Processo per la preparazione di tetraazamacrocicli |
IT1290457B1 (it) * | 1997-04-04 | 1998-12-03 | Bracco Spa | Processo per la preparazione di tetraazamacrocicli |
IT1291673B1 (it) * | 1997-04-28 | 1999-01-19 | Bracco Spa | Processo per la preparazione di 1,4,7,10 - tetraazaciclododecano |
IT1293777B1 (it) * | 1997-07-25 | 1999-03-10 | Bracco Spa | Processo per la preparazione di tetraazamacrocicli |
DE19809543A1 (de) * | 1998-03-05 | 1999-09-09 | Clariant Gmbh | Verfahren zur Herstellung von makropolycyclischen Polymaninen |
DE19809542A1 (de) * | 1998-03-05 | 1999-09-09 | Clariant Gmbh | Quaternäre polycyclische Polyammoniumsalze und Verfahren zu deren Herstellung |
DE19856481C1 (de) * | 1998-12-02 | 2000-07-06 | Schering Ag | Verfahren zur Herstellung von Cyclen |
US6156890A (en) * | 1999-01-15 | 2000-12-05 | Schering Aktiengesellschaft | Process for the production of cyclene |
IT1309601B1 (it) * | 1999-03-09 | 2002-01-24 | Bracco Spa | Processo per la preparazione di 1,4,7,10 tetraazaciclododecano. |
US6685914B1 (en) * | 1999-09-13 | 2004-02-03 | Bristol-Myers Squibb Pharma Company | Macrocyclic chelants for metallopharmaceuticals |
US7067111B1 (en) | 1999-10-25 | 2006-06-27 | Board Of Regents, University Of Texas System | Ethylenedicysteine (EC)-drug conjugates, compositions and methods for tissue specific disease imaging |
DK1286704T3 (da) | 2000-06-02 | 2014-09-22 | Univ Texas | Ethylendicystein (EC)-glucose analoge konjugater |
FR2810035B1 (fr) * | 2000-06-13 | 2004-04-16 | Air Liquide | Procede de preparation de tetraaza macrocycles et nouveaux composes |
US7498432B2 (en) | 2003-06-25 | 2009-03-03 | Board Of Trustees Of Michigan State University | Method of synthesis of 1, 4, 7, 10, 13, 16, 21, 24-octaazabicyclo [8.8.8] hexacosane (1) and 1, 4, 7, 10, 13, 16, 21, 24-octaazabicyclo [8.8.8] hexacosa, 4, 6, 13, 15, 21, 23-hexaene (2) |
US9050378B2 (en) * | 2003-12-10 | 2015-06-09 | Board Of Regents, The University Of Texas System | N2S2 chelate-targeting ligand conjugates |
DE102004003710A1 (de) * | 2004-01-24 | 2005-08-11 | Clariant Gmbh | Verwendung von Übergangsmetallkomplexen als Bleichkatalysatoren in Wasch- und Reinigungsmitteln |
US8758723B2 (en) * | 2006-04-19 | 2014-06-24 | The Board Of Regents Of The University Of Texas System | Compositions and methods for cellular imaging and therapy |
US10925977B2 (en) * | 2006-10-05 | 2021-02-23 | Ceil>Point, LLC | Efficient synthesis of chelators for nuclear imaging and radiotherapy: compositions and applications |
US20100104511A1 (en) * | 2006-11-22 | 2010-04-29 | The Board Of Regents Of The University Of Texas System | Methods and compositions using chelator-antibody conjugates |
BRPI0809442A2 (pt) | 2007-03-27 | 2014-09-09 | Radiomedix Inc | Composições para terapia e formação de imagens direcionada |
US11473032B2 (en) | 2010-02-02 | 2022-10-18 | Fuchs Petrolub Se | Constant velocity joint having a boot |
DK2721045T3 (en) | 2011-06-20 | 2017-07-24 | Radiomedix Inc | COMPOSITIONS, METHODS OF SYNTHESIS AND USE OF CARBOHYDRATE TARGETED AGENTS |
CN103360333B (zh) * | 2013-07-22 | 2016-03-30 | 厦门市华兴化工有限公司 | 一种高纯度轮环藤宁的制备方法 |
CN104387336B (zh) * | 2014-10-24 | 2016-04-27 | 上海应用技术学院 | 1,4,7,10-四氮杂环十二烷及其纳滤膜的制备方法 |
IL271681A (en) | 2018-07-18 | 2020-01-30 | Vyripharm Entpr Llc | Systems and methods for integrated and comprehensive management of cannabis products |
CN113801123B (zh) * | 2021-10-18 | 2022-12-09 | 苏州百灵威超精细材料有限公司 | 一种1,4,8,11-四氮杂环十四烷类化合物及其中间体的制备方法 |
CN113956262B (zh) * | 2021-10-18 | 2023-03-07 | 苏州百灵威超精细材料有限公司 | 一种四氮杂环烷类化合物及其中间体的合成方法 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3485818A (en) * | 1968-04-05 | 1969-12-23 | Jerome B Thompson | 1,4,7,10-tetraazacyclododecene and 1,4,7,10,13 - pentaazacyclopentadecene and process for their manufacture |
US3932451A (en) * | 1973-11-27 | 1976-01-13 | E. I. Du Pont De Nemours & Company | 1,4,7,10-Tetraazatetracyclo[5.5.1.04,13.010,13 ]tridecane and its conjugate acids |
FR2654102B1 (fr) * | 1989-11-09 | 1992-01-10 | Air Liquide | Procede de synthese de derives polyazotes cycliques. |
US5587451A (en) * | 1993-11-26 | 1996-12-24 | The Dow Chemical Company | Process for preparing polyazamacrocycles |
GB9504922D0 (en) * | 1995-03-10 | 1995-04-26 | Nycomed As | Process |
IT1284046B1 (it) * | 1996-06-21 | 1998-05-08 | Bracco Spa | Processo per la preparazione di tetraazamacrocicli |
-
1996
- 1996-06-21 IT IT96MI001257A patent/IT1284046B1/it active IP Right Grant
-
1997
- 1997-06-09 HU HU9903380A patent/HU223439B1/hu active IP Right Grant
- 1997-06-09 DE DE69715211T patent/DE69715211T2/de not_active Expired - Lifetime
- 1997-06-09 EP EP97928162A patent/EP0914320B1/en not_active Expired - Lifetime
- 1997-06-09 ES ES97928162T patent/ES2183185T3/es not_active Expired - Lifetime
- 1997-06-09 WO PCT/EP1997/002987 patent/WO1997049691A1/en active IP Right Grant
- 1997-06-09 CA CA002258768A patent/CA2258768C/en not_active Expired - Lifetime
- 1997-06-09 CZ CZ19984210A patent/CZ295406B6/cs not_active IP Right Cessation
- 1997-06-09 JP JP50219498A patent/JP4308323B2/ja not_active Expired - Lifetime
- 1997-06-09 AT AT97928162T patent/ATE223389T1/de not_active IP Right Cessation
- 1997-06-09 AU AU32564/97A patent/AU3256497A/en not_active Abandoned
- 1997-06-09 CN CN97195647A patent/CN1083442C/zh not_active Expired - Lifetime
- 1997-06-19 ZA ZA9705425A patent/ZA975425B/xx unknown
- 1997-06-19 US US08/878,508 patent/US5880281A/en not_active Expired - Lifetime
- 1997-06-19 IN IN1333MA1997 patent/IN183348B/en unknown
-
1998
- 1998-12-02 US US09/203,595 patent/US6114521A/en not_active Expired - Lifetime
- 1998-12-02 US US09/203,604 patent/US6013793A/en not_active Expired - Lifetime
- 1998-12-18 NO NO19985992A patent/NO310621B1/no not_active IP Right Cessation
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006527241A (ja) * | 2003-06-13 | 2006-11-30 | サントル ナシオナル ドゥ ラ ルシェルシェサイアンティフィク(セエヌエールエス) | シス−8b−メチルデカヒドロ−2a,4a,6a,8a−テトラアザシクロペンタ[fg]アセナフチレン、シス−デカヒドロ−2a,4a,6a,8a−テトラアザシクロペンタ[fg]アセナフチレン、サイクレンおよび官能化サイクレン |
Also Published As
Publication number | Publication date |
---|---|
NO985992L (no) | 1999-02-22 |
EP0914320B1 (en) | 2002-09-04 |
EP0914320A1 (en) | 1999-05-12 |
ATE223389T1 (de) | 2002-09-15 |
JP4308323B2 (ja) | 2009-08-05 |
CN1083442C (zh) | 2002-04-24 |
HUP9903380A3 (en) | 2001-07-30 |
CN1222147A (zh) | 1999-07-07 |
ITMI961257A1 (it) | 1997-12-21 |
NO985992D0 (no) | 1998-12-18 |
US6013793A (en) | 2000-01-11 |
CA2258768A1 (en) | 1997-12-31 |
WO1997049691A1 (en) | 1997-12-31 |
CZ421098A3 (cs) | 1999-06-16 |
ES2183185T3 (es) | 2003-03-16 |
DE69715211T2 (de) | 2003-08-07 |
ITMI961257A0 (ja) | 1996-06-21 |
CZ295406B6 (cs) | 2005-08-17 |
IT1284046B1 (it) | 1998-05-08 |
ZA975425B (en) | 1998-01-26 |
IN183348B (ja) | 1999-11-27 |
HU223439B1 (hu) | 2004-07-28 |
US6114521A (en) | 2000-09-05 |
US5880281A (en) | 1999-03-09 |
DE69715211D1 (de) | 2002-10-10 |
AU3256497A (en) | 1998-01-14 |
NO310621B1 (no) | 2001-07-30 |
CA2258768C (en) | 2009-03-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2000512642A (ja) | テトラアザマクロ環の製造方法 | |
JP4386471B2 (ja) | 1,4,7,10−テトラアザビシクロ[8.2.2]テトラデカン−2−オン、その製造方法及びテトラアザ大員環の製造のためのその使用 | |
JP4399163B2 (ja) | N−(1−ヒドロキシメチル−2,3−ジヒドロキシプロピル)−1,4,7−トリスカルボキシメチル−1,4,7,10−テトラアザシクロドデカンのリチウム錯体、その製造及び使用 | |
JP4536919B2 (ja) | キレート化剤としての1,4,7,10−テトラアザシクロドデカン−1,4−二酢酸誘導体 | |
JP2023062038A (ja) | ガドブトロールの製造方法 | |
JP4563517B2 (ja) | テトラアザ大員環の製造方法 | |
JPS61183286A (ja) | 2‐アルコキシ‐n‐(1‐アザビシクロ〔2,2,2〕オクタン‐3‐イル)アミノベンズアミドの製法 | |
JP4460766B2 (ja) | 1,4,7,10−テトラアザシクロドデカン−1,4−二酢酸 | |
JP4320060B2 (ja) | テトラアザ大環状体の製造方法 | |
PL190121B1 (pl) | Sposób wytwarzania tetraazamakrocykli oraz ich sole: nadchloran i chlorek | |
JPH0696573B2 (ja) | 1,3‐ジヒドロ‐4‐ピリドイル‐2h‐イミダゾール‐2‐オンの製造 | |
JPS62142159A (ja) | 2−(4−〔(3−クロロ−5−ヨ−ド−2−ピリジニル)オキシ〕フエノキシ)プロピオン酸及びその誘導体並びにそれらの製造方法 | |
JPH01246282A (ja) | インドロキノリチジン誘導体 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040602 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080219 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20080212 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080430 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080616 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080619 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20081125 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090218 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20090421 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20090501 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120515 Year of fee payment: 3 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120515 Year of fee payment: 3 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130515 Year of fee payment: 4 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140515 Year of fee payment: 5 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
EXPY | Cancellation because of completion of term |