ES2873828T3 - Preparación y cristalización innovadoras de iosimenol - Google Patents
Preparación y cristalización innovadoras de iosimenol Download PDFInfo
- Publication number
- ES2873828T3 ES2873828T3 ES16798573T ES16798573T ES2873828T3 ES 2873828 T3 ES2873828 T3 ES 2873828T3 ES 16798573 T ES16798573 T ES 16798573T ES 16798573 T ES16798573 T ES 16798573T ES 2873828 T3 ES2873828 T3 ES 2873828T3
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- ES
- Spain
- Prior art keywords
- iosimenol
- crystallization
- process according
- crystal
- mixture
- 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.)
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- DLPPIGPJCKKVBA-UHFFFAOYSA-N Iosimenol Chemical compound OCC(O)CNC(=O)C1=C(I)C(C(=O)N)=C(I)C(N(CC(O)CO)C(=O)CC(=O)N(CC(O)CO)C=2C(=C(C(=O)NCC(O)CO)C(I)=C(C(N)=O)C=2I)I)=C1I DLPPIGPJCKKVBA-UHFFFAOYSA-N 0.000 title claims abstract description 144
- 229950004246 iosimenol Drugs 0.000 title claims abstract description 144
- 238000002425 crystallisation Methods 0.000 title claims description 72
- 230000008025 crystallization Effects 0.000 title claims description 70
- 238000002360 preparation method Methods 0.000 title claims description 14
- 239000013078 crystal Substances 0.000 claims abstract description 47
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 10
- 238000005259 measurement Methods 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims description 60
- 230000008569 process Effects 0.000 claims description 38
- 239000000203 mixture Substances 0.000 claims description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 16
- 239000011877 solvent mixture Substances 0.000 claims description 15
- 150000007529 inorganic bases Chemical class 0.000 claims description 12
- 238000002604 ultrasonography Methods 0.000 claims description 12
- CTKINSOISVBQLD-UHFFFAOYSA-N Glycidol Chemical compound OCC1CO1 CTKINSOISVBQLD-UHFFFAOYSA-N 0.000 claims description 10
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 10
- -1 2,3-dihydroxypropyl group Chemical group 0.000 claims description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 229910001507 metal halide Inorganic materials 0.000 claims description 7
- 150000005309 metal halides Chemical class 0.000 claims description 7
- ARXJGSRGQADJSQ-UHFFFAOYSA-N 1-methoxypropan-2-ol Chemical compound COCC(C)O ARXJGSRGQADJSQ-UHFFFAOYSA-N 0.000 claims description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 6
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 6
- 239000007858 starting material Substances 0.000 claims description 6
- 229940100198 alkylating agent Drugs 0.000 claims description 5
- 239000002168 alkylating agent Substances 0.000 claims description 5
- 150000002170 ethers Chemical class 0.000 claims description 5
- 125000001931 aliphatic group Chemical group 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 claims description 3
- 229940093475 2-ethoxyethanol Drugs 0.000 claims description 3
- HCGFUIQPSOCUHI-UHFFFAOYSA-N 2-propan-2-yloxyethanol Chemical compound CC(C)OCCO HCGFUIQPSOCUHI-UHFFFAOYSA-N 0.000 claims description 3
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical class CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 claims description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 3
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 claims description 3
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical class CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 claims description 3
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 3
- 229960000281 trometamol Drugs 0.000 claims description 3
- 239000000920 calcium hydroxide Substances 0.000 claims description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 239000000243 solution Substances 0.000 description 25
- 239000000523 sample Substances 0.000 description 20
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 229960004063 propylene glycol Drugs 0.000 description 12
- 239000000843 powder Substances 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 239000002872 contrast media Substances 0.000 description 8
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 8
- 229910052753 mercury Inorganic materials 0.000 description 8
- 239000002245 particle Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- SSZWWUDQMAHNAQ-UHFFFAOYSA-N 3-chloropropane-1,2-diol Chemical compound OCC(O)CCl SSZWWUDQMAHNAQ-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 239000012043 crude product Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 239000001307 helium Substances 0.000 description 4
- 229910052734 helium Inorganic materials 0.000 description 4
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 4
- 210000003739 neck Anatomy 0.000 description 4
- 238000010899 nucleation Methods 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 238000001694 spray drying Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 101000599782 Homo sapiens Insulin-like growth factor 2 mRNA-binding protein 3 Proteins 0.000 description 3
- 101000702394 Homo sapiens Signal peptide peptidase-like 2A Proteins 0.000 description 3
- 101000960621 Homo sapiens U3 small nucleolar ribonucleoprotein protein IMP3 Proteins 0.000 description 3
- 101710125768 Importin-4 Proteins 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 102100030403 Signal peptide peptidase-like 2A Human genes 0.000 description 3
- 102100030404 Signal peptide peptidase-like 2B Human genes 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 229940039231 contrast media Drugs 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 238000001728 nano-filtration Methods 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 238000004626 scanning electron microscopy Methods 0.000 description 3
- 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 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 2
- JHNIODKBMLOUFY-UHFFFAOYSA-N 5-[[3-[3-carbamoyl-5-(2,3-dihydroxypropylcarbamoyl)-2,4,6-triiodoanilino]-3-oxopropanoyl]amino]-3-n-(2,3-dihydroxypropyl)-2,4,6-triiodobenzene-1,3-dicarboxamide Chemical compound OCC(O)CNC(=O)C1=C(I)C(C(=O)N)=C(I)C(NC(=O)CC(=O)NC=2C(=C(C(=O)NCC(O)CO)C(I)=C(C(N)=O)C=2I)I)=C1I JHNIODKBMLOUFY-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 101000599778 Homo sapiens Insulin-like growth factor 2 mRNA-binding protein 1 Proteins 0.000 description 2
- 101000988591 Homo sapiens Minor histocompatibility antigen H13 Proteins 0.000 description 2
- 101000960626 Homo sapiens Mitochondrial inner membrane protease subunit 2 Proteins 0.000 description 2
- 101000828788 Homo sapiens Signal peptide peptidase-like 3 Proteins 0.000 description 2
- XOBKSJJDNFUZPF-UHFFFAOYSA-N Methoxyethane Chemical compound CCOC XOBKSJJDNFUZPF-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 102100029083 Minor histocompatibility antigen H13 Human genes 0.000 description 2
- 102100023501 Signal peptide peptidase-like 3 Human genes 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000003957 anion exchange resin Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000003729 cation exchange resin Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000011549 crystallization solution Substances 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000002242 deionisation method Methods 0.000 description 2
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- NKDDWNXOKDWJAK-UHFFFAOYSA-N dimethoxymethane Chemical compound COCOC NKDDWNXOKDWJAK-UHFFFAOYSA-N 0.000 description 2
- 239000000428 dust Substances 0.000 description 2
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 229960004592 isopropanol Drugs 0.000 description 2
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 2
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000002459 porosimetry Methods 0.000 description 2
- 238000001812 pycnometry Methods 0.000 description 2
- 238000001223 reverse osmosis Methods 0.000 description 2
- 238000001878 scanning electron micrograph Methods 0.000 description 2
- 239000011343 solid material Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- NUMQCACRALPSHD-UHFFFAOYSA-N tert-butyl ethyl ether Chemical compound CCOC(C)(C)C NUMQCACRALPSHD-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- SIBFQOUHOCRXDL-UHFFFAOYSA-N 3-bromopropane-1,2-diol Chemical compound OCC(O)CBr SIBFQOUHOCRXDL-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 101100152504 Arabidopsis thaliana TAX2 gene Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- WGQMHVQCBWYFRX-UHFFFAOYSA-N Cc(c(C(N)=O)c(c(C(NCC(CO)O)=O)c1I)I)c1N(CC(CO)O)C(CC(N(CC(CO)O)c(c(I)c(C(N)=O)c(I)c1C(NCC(CO)O)=O)c1I)=O)=O Chemical compound Cc(c(C(N)=O)c(c(C(NCC(CO)O)=O)c1I)I)c1N(CC(CO)O)C(CC(N(CC(CO)O)c(c(I)c(C(N)=O)c(I)c1C(NCC(CO)O)=O)c1I)=O)=O WGQMHVQCBWYFRX-UHFFFAOYSA-N 0.000 description 1
- 102100024342 Contactin-2 Human genes 0.000 description 1
- 229910016523 CuKa Inorganic materials 0.000 description 1
- 101000909516 Homo sapiens Contactin-2 Proteins 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000003763 carbonization Methods 0.000 description 1
- 229940023913 cation exchange resins Drugs 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- RKTYLMNFRDHKIL-UHFFFAOYSA-N copper;5,10,15,20-tetraphenylporphyrin-22,24-diide Chemical compound [Cu+2].C1=CC(C(=C2C=CC([N-]2)=C(C=2C=CC=CC=2)C=2C=CC(N=2)=C(C=2C=CC=CC=2)C2=CC=C3[N-]2)C=2C=CC=CC=2)=NC1=C3C1=CC=CC=C1 RKTYLMNFRDHKIL-UHFFFAOYSA-N 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 238000011157 data evaluation Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001887 electron backscatter diffraction Methods 0.000 description 1
- 238000002003 electron diffraction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- NBQNWMBBSKPBAY-UHFFFAOYSA-N iodixanol Chemical compound IC=1C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C(I)C=1N(C(=O)C)CC(O)CN(C(C)=O)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NBQNWMBBSKPBAY-UHFFFAOYSA-N 0.000 description 1
- 229960004359 iodixanol Drugs 0.000 description 1
- NTHXOOBQLCIOLC-UHFFFAOYSA-N iohexol Chemical compound OCC(O)CN(C(=O)C)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NTHXOOBQLCIOLC-UHFFFAOYSA-N 0.000 description 1
- 229960001025 iohexol Drugs 0.000 description 1
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 125000000346 malonyl group Chemical group C(CC(=O)*)(=O)* 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000001683 neutron diffraction Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 238000001144 powder X-ray diffraction data Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
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- 230000035484 reaction time Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000013074 reference sample Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
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- 238000005011 time of flight secondary ion mass spectroscopy Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/46—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having carbon atoms of carboxamide groups, amino groups and at least three atoms of bromine or iodine, bound to carbon atoms of the same non-condensed six-membered aromatic ring
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D9/00—Crystallisation
- B01D9/005—Selection of auxiliary, e.g. for control of crystallisation nuclei, of crystal growth, of adherence to walls; Arrangements for introduction thereof
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D9/00—Crystallisation
- B01D9/0081—Use of vibrations, e.g. ultrasound
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
- B01J19/10—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing sonic or ultrasonic vibrations
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/08—Preparation of carboxylic acid amides from amides by reaction at nitrogen atoms of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D9/00—Crystallisation
- B01D2009/0086—Processes or apparatus therefor
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00049—Controlling or regulating processes
- B01J2219/00051—Controlling the temperature
- B01J2219/00139—Controlling the temperature using electromagnetic heating
- B01J2219/00141—Microwaves
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Crystallography & Structural Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Toxicology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562250720P | 2015-11-04 | 2015-11-04 | |
| PCT/JP2016/004798 WO2017077710A1 (en) | 2015-11-04 | 2016-11-02 | Innovative preparation and crystallization of iosimenol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2873828T3 true ES2873828T3 (es) | 2021-11-04 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES16798573T Active ES2873828T3 (es) | 2015-11-04 | 2016-11-02 | Preparación y cristalización innovadoras de iosimenol |
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| US (1) | US10544089B2 (enExample) |
| EP (1) | EP3371147B1 (enExample) |
| JP (1) | JP6778746B2 (enExample) |
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| TW (1) | TWI724049B (enExample) |
| WO (1) | WO2017077710A1 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102128423B1 (ko) * | 2018-09-17 | 2020-07-01 | (주)유케이케미팜 | 조영제 이오메프롤의 제조방법 |
| CN111777525B (zh) * | 2019-04-04 | 2021-08-27 | 成都西岭源药业有限公司 | 一种碘克沙醇的精制方法 |
| KR102179649B1 (ko) * | 2019-10-11 | 2020-11-18 | (주)에이에스텍 | 디에틸아미노하이드록시벤조일헥실벤조에이트의 제조 방법 |
| CN115931935A (zh) * | 2022-12-28 | 2023-04-07 | 深圳晶泰科技有限公司 | 一种提高微晶电子衍射数据质量的方法 |
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| US5698739A (en) * | 1989-07-05 | 1997-12-16 | Schering Aktiengesellschaft | Carboxamide non-ionic contrast media |
| US6072069A (en) * | 1998-11-04 | 2000-06-06 | Biophysica, Inc. | Biodegradable nonionic contrast media |
| NO20053687D0 (no) * | 2005-07-29 | 2005-07-29 | Amersham Health As | Crystallisation Process. |
| JP2011509943A (ja) * | 2008-01-14 | 2011-03-31 | マリンクロッド・インコーポレイテッド | イオシメノールを調製するためのプロセス |
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2016
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Also Published As
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| KR20180077198A (ko) | 2018-07-06 |
| NZ742104A (en) | 2023-01-27 |
| HK1257821A1 (en) | 2019-11-01 |
| EP3371147B1 (en) | 2021-04-07 |
| AU2021205101A1 (en) | 2021-08-19 |
| PL3371147T3 (pl) | 2021-10-25 |
| SG11201803241YA (en) | 2018-05-30 |
| TW201722906A (zh) | 2017-07-01 |
| DK3371147T3 (da) | 2021-05-25 |
| JP6778746B2 (ja) | 2020-11-04 |
| US10544089B2 (en) | 2020-01-28 |
| HRP20210820T1 (hr) | 2021-06-25 |
| CN108368031B (zh) | 2022-05-03 |
| MY186399A (en) | 2021-07-22 |
| PT3371147T (pt) | 2021-05-24 |
| AU2016350219B2 (en) | 2021-04-29 |
| WO2017077710A1 (en) | 2017-05-11 |
| SA518391413B1 (ar) | 2022-03-06 |
| AU2021205101B2 (en) | 2022-11-24 |
| CN108368031A (zh) | 2018-08-03 |
| EP3371147A1 (en) | 2018-09-12 |
| PH12018500872A1 (en) | 2018-11-05 |
| LT3371147T (lt) | 2021-08-10 |
| TWI724049B (zh) | 2021-04-11 |
| US20190177266A1 (en) | 2019-06-13 |
| HUE054876T2 (hu) | 2021-10-28 |
| CY1124164T1 (el) | 2022-05-27 |
| AU2016350219A1 (en) | 2018-05-17 |
| CA3002502A1 (en) | 2017-05-11 |
| JP2018536654A (ja) | 2018-12-13 |
| SI3371147T1 (sl) | 2021-08-31 |
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