IL105807A - Processes for preparing the history of Tetraazacyclododecain and Tetraazacyclotodracan - Google Patents

Processes for preparing the history of Tetraazacyclododecain and Tetraazacyclotodracan

Info

Publication number: IL105807A
Authority: IL; Israel
Prior art keywords: optionally; process according; tetraazacyclododecane; hydrogen; hydroxy
Prior art date: 1992-06-04

Application number

IL10580793A

Other languages

English (en)

Hebrew (he)

Other versions

IL105807A0 (en

Original Assignee

Schering Ag

Priority date (The priority date 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 date listed.)

1992-06-04

Filing date

1993-05-25

Publication date

1998-12-06

1993-05-25 Application filed by Schering Ag filed Critical Schering Ag

1993-09-22 Publication of IL105807A0 publication Critical patent/IL105807A0/xx

1998-12-06 Publication of IL105807A publication Critical patent/IL105807A/en

Links

238000000034 method Methods 0.000 title claims abstract description 49
230000008569 process Effects 0.000 title claims abstract description 41
238000002360 preparation method Methods 0.000 title description 2
238000004519 manufacturing process Methods 0.000 claims abstract description 11
229910052751 metal Inorganic materials 0.000 claims abstract description 8
239000002184 metal Substances 0.000 claims abstract description 8
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical group CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 52
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 51
-1 C^-^-alkyl Chemical group 0.000 claims description 45
238000006243 chemical reaction Methods 0.000 claims description 37
150000001875 compounds Chemical class 0.000 claims description 20
239000002253 acid Substances 0.000 claims description 19
125000006239 protecting group Chemical group 0.000 claims description 19
239000001257 hydrogen Substances 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
150000003839 salts Chemical class 0.000 claims description 16
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
150000002431 hydrogen Chemical group 0.000 claims description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 9
QBPPRVHXOZRESW-UHFFFAOYSA-N 1,4,7,10-tetraazacyclododecane Chemical compound C1CNCCNCCNCCN1 QBPPRVHXOZRESW-UHFFFAOYSA-N 0.000 claims description 8
125000000217 alkyl group Chemical group 0.000 claims description 8
150000002148 esters Chemical class 0.000 claims description 8
239000002904 solvent Substances 0.000 claims description 8
150000001413 amino acids Chemical class 0.000 claims description 7
MDAXKAUIABOHTD-UHFFFAOYSA-N 1,4,8,11-tetraazacyclotetradecane Chemical compound C1CNCCNCCCNCCNC1 MDAXKAUIABOHTD-UHFFFAOYSA-N 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
150000007529 inorganic bases Chemical class 0.000 claims description 6
150000007530 organic bases Chemical class 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
239000007858 starting material Substances 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 5
150000001408 amides Chemical class 0.000 claims description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 5
239000002798 polar solvent Substances 0.000 claims description 5
150000007513 acids Chemical class 0.000 claims description 4
229910021645 metal ion Inorganic materials 0.000 claims description 4
150000001768 cations Chemical group 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
229910044991 metal oxide Inorganic materials 0.000 claims description 3
150000004706 metal oxides Chemical class 0.000 claims description 3
150000007524 organic acids Chemical class 0.000 claims description 3
125000006515 benzyloxy alkyl group Chemical group 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims description 2
239000012535 impurity Substances 0.000 claims description 2
150000007522 mineralic acids Chemical class 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
150000002118 epoxides Chemical class 0.000 claims 6
125000000041 C6-C10 aryl group Chemical group 0.000 claims 1
241000790917 Dioxys <bee> Species 0.000 claims 1
238000005580 one pot reaction Methods 0.000 claims 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 75
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
239000012071 phase Substances 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
239000000243 solution Substances 0.000 description 23
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
239000000047 product Substances 0.000 description 19
239000008367 deionised water Substances 0.000 description 17
229910021641 deionized water Inorganic materials 0.000 description 17
238000001704 evaporation Methods 0.000 description 15
230000008020 evaporation Effects 0.000 description 15
239000000203 mixture Substances 0.000 description 14
238000004458 analytical method Methods 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
235000019441 ethanol Nutrition 0.000 description 12
229910052688 Gadolinium Inorganic materials 0.000 description 11
UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 11
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 9
150000002678 macrocyclic compounds Chemical class 0.000 description 9
150000002924 oxiranes Chemical class 0.000 description 9
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
239000002585 base Substances 0.000 description 8
FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 8
229940106681 chloroacetic acid Drugs 0.000 description 8
GEKNCWQQNMEIMS-UHFFFAOYSA-N 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane Chemical compound C1OC(C)(C)OCC2OC21 GEKNCWQQNMEIMS-UHFFFAOYSA-N 0.000 description 7
229960004756 ethanol Drugs 0.000 description 7
150000002500 ions Chemical class 0.000 description 7
239000012299 nitrogen atmosphere Substances 0.000 description 7
238000003756 stirring Methods 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
229920001429 chelating resin Polymers 0.000 description 6
238000003776 cleavage reaction Methods 0.000 description 6
239000012043 crude product Substances 0.000 description 6
238000002844 melting Methods 0.000 description 6
230000008018 melting Effects 0.000 description 6
239000000376 reactant Substances 0.000 description 6
230000007017 scission Effects 0.000 description 6
239000000126 substance Substances 0.000 description 6
229910021529 ammonia Inorganic materials 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
229940075613 gadolinium oxide Drugs 0.000 description 5
229910001938 gadolinium oxide Inorganic materials 0.000 description 5
CMIHHWBVHJVIGI-UHFFFAOYSA-N gadolinium(iii) oxide Chemical compound [O-2].[O-2].[O-2].[Gd+3].[Gd+3] CMIHHWBVHJVIGI-UHFFFAOYSA-N 0.000 description 5
239000012362 glacial acetic acid Substances 0.000 description 5
230000007935 neutral effect Effects 0.000 description 5
150000003254 radicals Chemical class 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
230000002378 acidificating effect Effects 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000013078 crystal Substances 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
125000004433 nitrogen atom Chemical group N* 0.000 description 4
230000001376 precipitating effect Effects 0.000 description 4
238000000926 separation method Methods 0.000 description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
NONMAFOOSQVPLW-UHFFFAOYSA-N 2-methyl-10-(1,3,4-trihydroxybutan-2-yl)-1,4,7,10-tetrazacyclododecane-1,4,7-tricarboxylic acid Chemical compound CC1CN(C(O)=O)CCN(C(O)=O)CCN(C(CO)C(O)CO)CCN1C(O)=O NONMAFOOSQVPLW-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
239000003513 alkali Substances 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
125000004181 carboxyalkyl group Chemical group 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
230000000536 complexating effect Effects 0.000 description 3
238000001816 cooling Methods 0.000 description 3
238000000605 extraction Methods 0.000 description 3
229910052744 lithium Inorganic materials 0.000 description 3
238000006386 neutralization reaction Methods 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
238000010992 reflux Methods 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
QYCOQFHNZDDLQW-UHFFFAOYSA-N sulfuric acid;1,4,7,10-tetrazacyclododecane Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.C1CNCCNCCNCCN1 QYCOQFHNZDDLQW-UHFFFAOYSA-N 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
150000004649 carbonic acid derivatives Chemical class 0.000 description 2
229940039231 contrast media Drugs 0.000 description 2
239000002872 contrast media Substances 0.000 description 2
JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
229940039227 diagnostic agent Drugs 0.000 description 2
239000000032 diagnostic agent Substances 0.000 description 2
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
238000004821 distillation Methods 0.000 description 2
238000001035 drying Methods 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
229940093915 gynecological organic acid Drugs 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
238000007327 hydrogenolysis reaction Methods 0.000 description 2
150000004679 hydroxides Chemical class 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
238000002955 isolation Methods 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
MJGFBOZCAJSGQW-UHFFFAOYSA-N mercury sodium Chemical compound [Na].[Hg] MJGFBOZCAJSGQW-UHFFFAOYSA-N 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
239000011707 mineral Substances 0.000 description 2
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
239000001103 potassium chloride Substances 0.000 description 2
235000011164 potassium chloride Nutrition 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
238000007127 saponification reaction Methods 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 1
HVSVGAVECUJPNC-UHFFFAOYSA-N 1,4,7,10-tetrazacyclododec-1-ylmethanetricarboxylic acid Chemical compound OC(=O)C(C(O)=O)(C(O)=O)N1CCNCCNCCNCC1 HVSVGAVECUJPNC-UHFFFAOYSA-N 0.000 description 1
SBWLCGZEBQGYRP-UHFFFAOYSA-N 1,4,7,10-tetrazacyclododecane;tetrahydrochloride Chemical compound Cl.Cl.Cl.Cl.C1CNCCNCCNCCN1 SBWLCGZEBQGYRP-UHFFFAOYSA-N 0.000 description 1
HRAIEHCQDDIRTO-UHFFFAOYSA-N 1-(1,4,7,10-tetrazacyclododec-1-yl)propan-2-ol;tetrahydrochloride Chemical compound Cl.Cl.Cl.Cl.CC(O)CN1CCNCCNCCNCC1 HRAIEHCQDDIRTO-UHFFFAOYSA-N 0.000 description 1
OSJPGDQYKUYREK-UHFFFAOYSA-N 1-(2,2-dimethyl-1,3-dioxolan-4-yl)-2-(1,4,7,10-tetrazacyclododec-1-yl)ethanol Chemical compound O1C(C)(C)OCC1C(O)CN1CCNCCNCCNCC1 OSJPGDQYKUYREK-UHFFFAOYSA-N 0.000 description 1
FRELRIWZBXADCT-UHFFFAOYSA-N 2,2-dimethyl-6-(1,4,7,10-tetrazacyclododec-1-yl)-1,3-dioxepan-5-ol Chemical compound C1OC(C)(C)OCC(O)C1N1CCNCCNCCNCC1 FRELRIWZBXADCT-UHFFFAOYSA-N 0.000 description 1
ULYDPFYLCOXMBQ-UHFFFAOYSA-N 2-[4,7-bis(carboxymethyl)-10-(2,3,4-trihydroxybutyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid Chemical compound OCC(O)C(O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1 ULYDPFYLCOXMBQ-UHFFFAOYSA-N 0.000 description 1
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
NXHUAYWRBFCZOA-UHFFFAOYSA-N 3-(1,4,7,10-tetrazacyclododec-1-yl)butane-1,2,4-triol Chemical compound OCC(O)C(CO)N1CCNCCNCCNCC1 NXHUAYWRBFCZOA-UHFFFAOYSA-N 0.000 description 1
FYFSGGAVTBSKBV-UHFFFAOYSA-N 3-(1,4,7,10-tetrazacyclododec-1-yl)butane-1,2,4-triol;tetrahydrochloride Chemical compound Cl.Cl.Cl.Cl.OCC(O)C(CO)N1CCNCCNCCNCC1 FYFSGGAVTBSKBV-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
PXACTUVBBMDKRW-UHFFFAOYSA-M 4-bromobenzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-M 0.000 description 1
SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
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
ZNYRFEPBTVGZDN-UHFFFAOYSA-N 5S,6S-epoxy-15R-hydroxy-ETE Chemical compound COCCOCCOCCOCCO ZNYRFEPBTVGZDN-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
XFJUHPLPVKUBII-UHFFFAOYSA-N Cl.Cl.Cl.Cl.OC(C(C(O)C)O)N1CCNCCNCCNCC1 Chemical compound Cl.Cl.Cl.Cl.OC(C(C(O)C)O)N1CCNCCNCCNCC1 XFJUHPLPVKUBII-UHFFFAOYSA-N 0.000 description 1
OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
239000004593 Epoxy Substances 0.000 description 1
IQUHNCOJRJBMSU-UHFFFAOYSA-N H3HP-DO3A Chemical compound CC(O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1 IQUHNCOJRJBMSU-UHFFFAOYSA-N 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
AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
238000005684 Liebig rearrangement reaction Methods 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
238000010306 acid treatment Methods 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
159000000032 aromatic acids Chemical class 0.000 description 1
125000003710 aryl alkyl group Chemical group 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
229910052788 barium Inorganic materials 0.000 description 1
DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
229910001863 barium hydroxide Inorganic materials 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
150000001767 cationic compounds Chemical class 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000002704 decyl 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])C([H])([H])C([H])([H])* 0.000 description 1
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
229940113088 dimethylacetamide Drugs 0.000 description 1
238000005868 electrolysis reaction Methods 0.000 description 1
229940031098 ethanolamine Drugs 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
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 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
125000002768 hydroxyalkyl group Chemical group 0.000 description 1
238000003384 imaging method Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
229960004592 isopropanol Drugs 0.000 description 1
125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000003446 ligand Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
125000001421 myristyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
HTTVKDXKMFLICX-UHFFFAOYSA-N n-[2-(2-aminoethylamino)ethyl]-4-methylbenzenesulfonamide Chemical compound CC1=CC=C(S(=O)(=O)NCCNCCN)C=C1 HTTVKDXKMFLICX-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
150000002892 organic cations Chemical class 0.000 description 1
229960003104 ornithine Drugs 0.000 description 1
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
239000008188 pellet Substances 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
BITYAPCSNKJESK-UHFFFAOYSA-N potassiosodium Chemical compound [Na].[K] BITYAPCSNKJESK-UHFFFAOYSA-N 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
229960005335 propanol Drugs 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
238000006894 reductive elimination reaction Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910001023 sodium amalgam Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
JLGLQAWTXXGVEM-UHFFFAOYSA-N triethylene glycol monomethyl ether Chemical compound COCCOCCOCCO JLGLQAWTXXGVEM-UHFFFAOYSA-N 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- 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)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

IL10580793A 1992-06-04 1993-05-25 Processes for preparing the history of Tetraazacyclododecain and Tetraazacyclotodracan IL105807A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE4218744A DE4218744C2 (de)	1992-06-04	1992-06-04	Verfahren zur Herstellung von N-ß-Hxdroxyalkyl-tri-N-carboxylalkyl-1,4,7,10-tetraazacyclododecan- und N-ß-Hydroxyalkyl-tri-N-carboxyalkyl-1,4,8,11-tetraazacyclotetradecan-Derivaten und deren Metallkomplexe

Publications (2)

Publication Number	Publication Date
IL105807A0 IL105807A0 (en)	1993-09-22
IL105807A true IL105807A (en)	1998-12-06

Family

ID=6460555

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL10580793A IL105807A (en)	1992-06-04	1993-05-25	Processes for preparing the history of Tetraazacyclododecain and Tetraazacyclotodracan

Country Status (16)

Country	Link
US (1)	US5386028A (fr)
EP (1)	EP0643705B1 (fr)
JP (1)	JP3565843B2 (fr)
KR (1)	KR100269081B1 (fr)
AT (1)	ATE178321T1 (fr)
CA (1)	CA2137243C (fr)
CZ (1)	CZ282873B6 (fr)
DE (2)	DE4218744C2 (fr)
DK (1)	DK0643705T3 (fr)
ES (1)	ES2131582T3 (fr)
GR (1)	GR3030604T3 (fr)
HU (1)	HU213951B (fr)
IL (1)	IL105807A (fr)
NO (1)	NO302232B1 (fr)
SK (1)	SK281901B6 (fr)
WO (1)	WO1993024469A1 (fr)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE4317588C2 (de) *	1993-05-24	1998-04-16	Schering Ag	Fluorhaltige makrocyclische Metallkomplexe, Verfahren zu ihrer Herstellung, sowie ihre Verwendung
DE4318369C1 (de) *	1993-05-28	1995-02-09	Schering Ag	Verwendung von makrocyclischen Metallkomplexen als Temperatursonden
FR2725449B1 (fr) *	1994-10-05	1996-12-27	Air Liquide	Derives de polyazacycloalcanes, leurs complexes metalliques et produits pharmaceutiques incorporant ces complexes
GB9504922D0 (en) *	1995-03-10	1995-04-26	Nycomed As	Process
JPH11507621A (ja) *	1995-06-07	1999-07-06	モンサントカンパニー	置換ポリアザ大環状化合物の製造法
JP3356289B2 (ja)	1995-06-26	2002-12-16	コンキャットリミティド	第一遷移系列元素に対してキレート化親和性および選択性のある化合物とその医療および診断への使用
US5608061A (en) *	1995-08-02	1997-03-04	Johnson Matthey Plc	Process for preparing 1,4,8,11-tetraazacyclotetradecane
US5834456A (en) *	1996-02-23	1998-11-10	The Dow Chemical Company	Polyazamacrocyclofluoromonoalkylphosphonic acids, and their complexes, for use as contrast agents
DE19652386A1 (de) *	1996-12-04	1998-06-10	Schering Ag	Verfahren zur Herstellung von Metallkomplexcarbonsäureamiden
US6045776A (en) *	1996-12-04	2000-04-04	Schering Aktiengesellschaft	Process for the production of metal-complex carboxylic acid amides
DE19724186C2 (de) *	1997-06-02	2002-07-18	Schering Ag	Verfahren zur Mono- und 1,7-Bis-N-ß-Hydroxyalkylierung von Cyclen und die entsprechenden N-ß-Hydroxyalkyl-1,4,7,10-tetraazacyclododecan-Li-Salz-Komplexe
IT1292130B1 (it) *	1997-06-11	1999-01-25	Bracco Spa	Processo per la preparazione dell'acido 1,4,7,10-tetraazaciclododecan -1,4,7-triacetico e suoi derivati
IT1292128B1 (it) *	1997-06-11	1999-01-25	Bracco Spa	Processo per la preparazione di chelanti macrociclici e loro chelati con ioni metallici paramagnetici
IT1297035B1 (it)	1997-12-30	1999-08-03	Bracco Spa	Derivati dell'acido 1,4,7,10-tetraazaciclododecan-1,4-diacetico
WO2005003105A1 (fr) *	2003-07-08	2005-01-13	The University Of Hong Kong	Synthese de 1,4,7,10-tetraaza-cyclododecanes tris n-alkyles
EP3269395A1 (fr)	2008-11-07	2018-01-17	Massachusetts Institute Of Technology	Lipidoïdes aminoalcool et leurs utilisations
DE102009053171B4 (de) *	2009-11-04	2011-07-21	Bayer Schering Pharma Aktiengesellschaft, 13353	Verfahren zur Herstellung des Calcium-Komplexes von Dihydroxy-hydroxy-methylpropyl-tetraazacyclododecan-triessigsäure (Calcobutrol)
EP2691443B1 (fr) *	2011-03-28	2021-02-17	Massachusetts Institute of Technology	Lipomères conjugués et utilisations associées
EP2896405B1 (fr) *	2011-04-21	2020-02-19	Bayer Intellectual Property GmbH	Préparation de gadobutrol de grande pureté
PE20181541A1 (es)	2011-10-27	2018-09-26	Massachusetts Inst Technology	Derivados de aminoacidos funcionalizados en la terminal n capaces de formar microesferas encapsuladoras de farmaco
EP3102566B1 (fr) *	2014-02-06	2018-09-12	T2Pharma GmbH	Procédé de purification de l'acide 1,4,7,10-tétraazacyclododécane-1,4,7,10-tétraacétique
KR101693400B1 (ko) *	2014-09-17	2017-01-05	에스티팜 주식회사	칼코부트롤의 제조방법
KR101653064B1 (ko) *	2014-12-26	2016-09-09	에스티팜 주식회사	가도부트롤의 제조방법
WO2016205691A1 (fr)	2015-06-19	2016-12-22	Massachusetts Institute Of Technology	2,5-pipérazinediones substituées par un alcényle, et leur utilisation dans des compositions destinées à l'administration d'un agent à un sujet ou une cellule
HRP20200922T1 (hr)	2016-09-27	2020-09-18	Bayer Pharma Aktiengesellschaft	Postupak za proizvodnju kristalnog oblika modifikacije a kalkobutrola
KR101971435B1 (ko) *	2017-08-29	2019-04-24	주식회사 엔지켐생명과학	가도부트롤 중간체 및 이를 이용한 가도부트롤의 제조 방법
KR102033964B1 (ko) *	2018-01-19	2019-10-18	주식회사 엔지켐생명과학	가도테리돌 중간체 및 이를 이용한 가도테리돌 제조방법
US12227527B2 (en) *	2018-07-10	2025-02-18	Biophore India Pharmaceuticals Pvt. Ltd	Process for the preparation of 2,2′,2″-(10-((2R,3S)-1,3,4-trihydroxy butan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid and its complexes
KR101979836B1 (ko) *	2019-01-02	2019-05-21	동국생명과학 주식회사	칼코부트롤의 제조방법
EP4565570A1 (fr) *	2022-08-01	2025-06-11	Portland State University	Agents de contraste à haute relaxivité et préparation stéréosélective
CN118702638B (zh) *	2024-06-13	2025-09-23	上海凌凯科技股份有限公司	1,4,7,10-四氮十二烷衍生物、制备方法及其在合成钆络合物中的应用

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3860576A (en) *	1972-04-26	1975-01-14	Dow Chemical Co	N-substituted-tetra-azacyclotetradecanes
US4085106A (en) *	1976-01-07	1978-04-18	E. I. Du Pont De Nemours And Company	Bicyclic and tricyclic trisaminomethanes
NO149961C (no) *	1981-06-01	1984-07-25	Borregaard Ind	Fremgangsmaate for fremstilling av n-(2-hydroksyetyl)-derivater av makrocykliske polyaminer, inneholdende flere nitrogenatomer i 1,4-forhold i ringen
DE3625417C2 (de) *	1986-07-28	1998-10-08	Schering Ag	Tetraazacyclododecan-Derivate
US5006643A (en) *	1987-06-24	1991-04-09	The Dow Chemical Company	Process for preparing isothiocyanato functionalized metal complexes
US5064956A (en) *	1987-06-24	1991-11-12	The Dow Chemical Company	Process for preparing mono-n-alkylated polyazamacrocycles
US4994560A (en) *	1987-06-24	1991-02-19	The Dow Chemical Company	Functionalized polyamine chelants and radioactive rhodium complexes thereof for conjugation to antibodies
CA1341373C (fr) *	1988-06-24	2002-07-02	Roberta C. Cheng	Agents chelateurs bifonctionnels macrocycliques, leurs complexes et leurs conjugues d'anticorps
PH31170A (en) *	1988-10-31	1998-03-20	Dow Chemical Co	Chelants possesing ortho ligating functionality and complexes thereof.
US4937333A (en) *	1989-08-04	1990-06-26	The Dow Chemical Company	Method for purifying aminomethylenephosphonic acids for pharmaceutical use
WO1990007261A2 (fr) *	1988-12-22	1990-07-12	The Dow Chemical Company	Procede de preparation de polyazamacrocycles mono-n-alkyles
WO1990007342A1 (fr) *	1988-12-23	1990-07-12	The Dow Chemical Company	Procede de preparation de complexes de metaux isothiocyanato fonctionnalises
DE69024826T2 (de) *	1989-02-10	1996-06-27	Celltech Therapeutics Ltd	Aza-Macrozyklen und Verfahren zu deren Herstellung
US5053503A (en) *	1989-02-17	1991-10-01	Centocor	Chelating agents
FR2644453A1 (fr) *	1989-03-20	1990-09-21	Centre Nat Rech Scient	Procede de preparation de tetramines cycliques monofonctionnalisees
US5064802A (en) *	1989-09-14	1991-11-12	The Dow Chemical Company	Metal complex compounds
AU625529B2 (en) *	1989-12-22	1992-07-16	E.R. Squibb & Sons, Inc.	10-(2'-hydroxy-3'-alkoxy-1,4,7-triscarboxymethyl-1,4,7,10- tetraazacyclododecanes
AU6709390A (en) *	1989-12-22	1991-06-27	E.R. Squibb & Sons, Inc.	10-(2'-hydroxy-3'-polyoxaalkyl)-1,4,7-tris-carboxymethyl -1,4,7,10-tetraazacyclododecane
DE4009119A1 (de) *	1990-03-19	1991-09-26	Schering Ag	1,4,7,10-tetraazacyclododecan-butyltriole, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische mittel
AU648315B2 (en) *	1990-06-18	1994-04-21	Dow Chemical Company, The	The use of macrocyclic aminophosphonic acid complexes as imaging agents
MC2260A1 (fr) *	1990-06-18	1993-04-26	Dow Chemical Co	Formulations de produits radiopharmaceutiques,leur methode d'administration et leur procede de preparation
IT1243801B (it) *	1990-08-29	1994-06-28	Bracco Ind Chimica Spa	Intermedi per agenti chelanti con simmetria prefissata, e procedimentoper la loro preparazione
DE4035760A1 (de) *	1990-11-08	1992-05-14	Schering Ag	Mono-n-substituierte 1,4,7,10-tetraazacyclododecan-derivate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische mittel

1992
- 1992-06-04 DE DE4218744A patent/DE4218744C2/de not_active Expired - Lifetime
1993
- 1993-02-11 US US08/016,452 patent/US5386028A/en not_active Expired - Lifetime
- 1993-05-25 IL IL10580793A patent/IL105807A/en not_active IP Right Cessation
- 1993-05-28 DE DE59309488T patent/DE59309488D1/de not_active Expired - Lifetime
- 1993-05-28 CZ CZ943015A patent/CZ282873B6/cs not_active IP Right Cessation
- 1993-05-28 DK DK93912835T patent/DK0643705T3/da active
- 1993-05-28 WO PCT/EP1993/001362 patent/WO1993024469A1/fr not_active Ceased
- 1993-05-28 HU HU9403464A patent/HU213951B/hu unknown
- 1993-05-28 CA CA002137243A patent/CA2137243C/fr not_active Expired - Lifetime
- 1993-05-28 SK SK1487-94A patent/SK281901B6/sk not_active IP Right Cessation
- 1993-05-28 KR KR1019940704411A patent/KR100269081B1/ko not_active Expired - Lifetime
- 1993-05-28 ES ES93912835T patent/ES2131582T3/es not_active Expired - Lifetime
- 1993-05-28 AT AT93912835T patent/ATE178321T1/de active
- 1993-05-28 EP EP93912835A patent/EP0643705B1/fr not_active Expired - Lifetime
- 1993-05-28 JP JP50021394A patent/JP3565843B2/ja not_active Expired - Lifetime
1994
- 1994-12-05 NO NO19944691A patent/NO302232B1/no not_active IP Right Cessation
1999
- 1999-06-23 GR GR990401687T patent/GR3030604T3/el unknown

Also Published As

Publication number	Publication date
CA2137243C (fr)	2005-09-20
HU213951B (en)	1997-11-28
JPH07507067A (ja)	1995-08-03
CA2137243A1 (fr)	1993-12-09
KR950701918A (ko)	1995-05-17
JP3565843B2 (ja)	2004-09-15
US5386028A (en)	1995-01-31
DK0643705T3 (da)	1999-10-25
NO302232B1 (no)	1998-02-09
EP0643705A1 (fr)	1995-03-22
HU9403464D0 (en)	1995-03-28
WO1993024469A1 (fr)	1993-12-09
KR100269081B1 (ko)	2000-10-16
NO944691L (no)	1994-12-05
CZ282873B6 (cs)	1997-11-12
CZ301594A3 (en)	1995-08-16
IL105807A0 (en)	1993-09-22
DE4218744C2 (de)	1997-11-06
GR3030604T3 (en)	1999-10-29
ATE178321T1 (de)	1999-04-15
DE4218744A1 (de)	1993-12-09
NO944691D0 (no)	1994-12-05
SK281901B6 (sk)	2001-09-11
SK148794A3 (en)	1995-07-11
ES2131582T3 (es)	1999-08-01
EP0643705B1 (fr)	1999-03-31
HUT71263A (en)	1995-11-28
DE59309488D1 (de)	1999-05-06

Legal Events

Date	Code	Title
1999-06-20	FF	Patent granted
1999-12-22	KB	Patent renewed
2003-07-06	KB	Patent renewed
2007-07-06	KB	Patent renewed
2011-06-30	KB	Patent renewed
2014-01-30	EXP	Patent expired

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EP0988294B1 (fr)	2005-11-02	Procede pour la preparation de chelateurs macrocycliques et chelates de ces derniers avec des ions metalliques paramagnetiques
US5410043A (en)	1995-04-25	Process for the production of mono-N-substituted tetraaza macrocycles
JP3727359B2 (ja)	2005-12-14	Ｎ−β−ヒドロキシアルキル−トリ−Ｎ−カルボキシアルキル−１，４，７，１０−テトラアザシクロドデカン−およびＮ−β−ヒドロキシアルキル−トリ−Ｎ−カルボキシアルキル−１，４，８，１１−テトラアザシクロテトラデカン−誘導体の金属錯体の製造方法
US6894151B2 (en)	2005-05-17	Lithium complexes of N-(1-hydroxymethyl-2,3-dihydroxypropyl)-1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecane, their production and use
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