CA2710573A1 - Un procede continu de preparation d'un intermediaire pour agents de contraste non ioniques pour rayons x - Google Patents

Un procede continu de preparation d'un intermediaire pour agents de contraste non ioniques pour rayons x Download PDF

Info

Publication number: CA2710573A1
Authority: CA; Canada
Prior art keywords: reactor; compound; aba; reaction; ionic
Prior art date: 2009-07-21
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.): Abandoned

Application number

CA 2710573

Other languages

English (en)

Inventor

Arne Askildsen

Lars Terje Holmaas

Thore Jarle Sorensen

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

GE Healthcare AS

Original Assignee

GE Healthcare AS

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.)

2009-07-21

Filing date

2010-07-20

Publication date

2011-01-21

2009-10-01 Priority claimed from US12/571,456 external-priority patent/US20110021834A1/en

2010-07-20 Application filed by GE Healthcare AS filed Critical GE Healthcare AS

2011-01-21 Publication of CA2710573A1 publication Critical patent/CA2710573A1/fr

Status Abandoned legal-status Critical Current

Links

238000010924 continuous production Methods 0.000 title abstract description 10
239000002872 contrast media Substances 0.000 title abstract description 6
150000001875 compounds Chemical class 0.000 claims abstract description 21
238000006192 iodination reaction Methods 0.000 claims abstract description 20
238000000034 method Methods 0.000 claims abstract description 11
KAEGSAWWVYMWIQ-UHFFFAOYSA-N 5-amino-1-n,3-n-bis(2,3-dihydroxypropyl)-2,4,6-triiodobenzene-1,3-dicarboxamide Chemical compound NC1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I KAEGSAWWVYMWIQ-UHFFFAOYSA-N 0.000 claims abstract description 3
238000002360 preparation method Methods 0.000 claims abstract description 3
XOZGAPXHJKSZCU-UHFFFAOYSA-N 5-amino-1-n,3-n-bis(2,3-dihydroxypropyl)benzene-1,3-dicarboxamide Chemical compound NC1=CC(C(=O)NCC(O)CO)=CC(C(=O)NCC(O)CO)=C1 XOZGAPXHJKSZCU-UHFFFAOYSA-N 0.000 claims description 12
QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 claims description 10
238000006243 chemical reaction Methods 0.000 claims description 7
239000003153 chemical reaction reagent Substances 0.000 claims description 6
238000001914 filtration Methods 0.000 claims description 6
238000010791 quenching Methods 0.000 claims description 6
230000000171 quenching effect Effects 0.000 claims description 6
230000003226 decolorizating effect Effects 0.000 claims description 5
239000013078 crystal Substances 0.000 claims description 4
239000000203 mixture Substances 0.000 claims description 4
238000001816 cooling Methods 0.000 claims description 3
239000011541 reaction mixture Substances 0.000 claims description 3
238000005406 washing Methods 0.000 claims description 3
230000002083 iodinating effect Effects 0.000 claims description 2
238000000746 purification Methods 0.000 abstract description 5
238000003786 synthesis reaction Methods 0.000 abstract description 4
230000015572 biosynthetic process Effects 0.000 abstract description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
230000026045 iodination Effects 0.000 description 6
239000000047 product Substances 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
238000004519 manufacturing process Methods 0.000 description 5
229960004359 iodixanol Drugs 0.000 description 4
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 4
238000001728 nano-filtration Methods 0.000 description 4
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 4
239000000243 solution Substances 0.000 description 4
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
238000010923 batch production Methods 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
238000001035 drying Methods 0.000 description 3
239000012452 mother liquor Substances 0.000 description 3
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 3
239000004289 sodium hydrogen sulphite Substances 0.000 description 3
AMDBBAQNWSUWGN-UHFFFAOYSA-N Ioversol Chemical compound OCCN(C(=O)CO)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I AMDBBAQNWSUWGN-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
238000005516 engineering process Methods 0.000 description 2
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 2
IUNJANQVIJDFTQ-UHFFFAOYSA-N iopentol Chemical compound COCC(O)CN(C(C)=O)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I IUNJANQVIJDFTQ-UHFFFAOYSA-N 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
230000005588 protonation Effects 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
LDOMKUVUXZRECL-UHFFFAOYSA-N 2-aminobenzene-1,3-dicarboxylic acid Chemical compound NC1=C(C(O)=O)C=CC=C1C(O)=O LDOMKUVUXZRECL-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
101100264174 Mus musculus Xiap gene Proteins 0.000 description 1
229910004878 Na2S2O4 Inorganic materials 0.000 description 1
229910004879 Na2S2O5 Inorganic materials 0.000 description 1
238000001069 Raman spectroscopy Methods 0.000 description 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
238000010586 diagram Methods 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000009776 industrial production Methods 0.000 description 1
125000006303 iodophenyl group Chemical group 0.000 description 1
229960001025 iohexol Drugs 0.000 description 1
229960000824 iopentol Drugs 0.000 description 1
229960004537 ioversol Drugs 0.000 description 1
238000011031 large-scale manufacturing process Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
FTQWRYSLUYAIRQ-UHFFFAOYSA-N n-[(octadecanoylamino)methyl]octadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NCNC(=O)CCCCCCCCCCCCCCCCC FTQWRYSLUYAIRQ-UHFFFAOYSA-N 0.000 description 1
238000010899 nucleation Methods 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
239000002904 solvent Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000010977 unit operation Methods 0.000 description 1

Landscapes

Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

CA 2710573 2009-07-21 2010-07-20 Un procede continu de preparation d'un intermediaire pour agents de contraste non ioniques pour rayons x Abandoned CA2710573A1 (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US22708509P	2009-07-21	2009-07-21
US61/227,085		2009-07-21
US12/571,456 US20110021834A1 (en)	2009-07-21	2009-10-01	Continuous process of preparing intermediate for non-ionic x-ray contrast agents
US12/571,456		2009-10-01

Publications (1)

Publication Number	Publication Date
CA2710573A1 true CA2710573A1 (fr)	2011-01-21

Family

ID=43495949

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA 2710573 Abandoned CA2710573A1 (fr)	2009-07-21	2010-07-20	Un procede continu de preparation d'un intermediaire pour agents de contraste non ioniques pour rayons x

Country Status (1)

Country	Link
CA (1)	CA2710573A1 (fr)

2010
- 2010-07-20 CA CA 2710573 patent/CA2710573A1/fr not_active Abandoned

Legal Events

Date	Code	Title	Description
2015-09-15	FZDE	Dead	Effective date: 20150721

Publication	Publication Date	Title
EP2281804A1 (fr)	2011-02-09	Procédé continu de préparation de 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide, un intermédiaire pour la synthèse d'agents de contraste à rayon x non ioniques
US20110021822A1 (en)	2011-01-27	continuous deacetylation and purification process in synthesis of non-ionic x-ray contrast agents
EP1960349B1 (fr)	2015-11-18	Purification de l'iodixanol
EP3077367B1 (fr)	2018-07-11	Procede alternatif pour la purification d'un intermediaire dans la synthese d'agents de contraste de rayons x non ioniques
US10011560B2 (en)	2018-07-03	Alternative process for the purification of an intermediate in the synthesis of non-ionic X-ray contrast agents
EP2289870B1 (fr)	2012-11-07	Procédé de purification du 5-amino-N,N'-bis(2,3-dihydroxypropyl)-isophthalamide , un intermédiaire pour la synthèse d'agents de contraste à rayon X non ioniques
CN105764882B (zh)	2018-03-30	合成非离子x射线造影剂的备选乙酰化方法
EP2281803A1 (fr)	2011-02-09	Améliorations de la cristallisation de 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6,-triiodo-isophthalamide, un intermédiaire pour la synthèse d'agents de contraste à rayon x non ioniques
CA2710102A1 (fr)	2011-01-21	Ameliorations de la cristallisation d'un intermediaire pour la synthese d'agents de contraste non ioniques pour rayons x
HK1227842A1 (en)	2017-10-27	Alternative process for the purification of an intermediate in the synthesis of non-ionic x-ray contrast agents
CA2710577C (fr)	2012-09-18	Cristallisation d'iodixanol par broyage
EP2281807A1 (fr)	2011-02-09	Décoloration de 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide, un intermédiaire de milieux de contraste
KR20110009044A (ko)	2011-01-27	조영제 중간체의 탈색법
HK1227842B (zh)	2020-04-24	纯化在非离子x-射线造影剂的合成中的中间体的供选方法
HK1227016A1 (en)	2017-10-13	Alternative process for the purification of an intermediate in the synthesis of non-ionic x-ray contrast agents
HK1227016B (zh)	2020-10-09	纯化非离子x射线造影剂合成中的中间体的备选方法