CA2710102A1 - Ameliorations de la cristallisation d'un intermediaire pour la synthese d'agents de contraste non ioniques pour rayons x - Google Patents

Ameliorations de la cristallisation d'un intermediaire pour la synthese d'agents de contraste non ioniques pour rayons x Download PDF

Info

Publication number: CA2710102A1
Authority: CA; Canada
Prior art keywords: compound; crystallization; bis; dihydroxypropyl; amino
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 2710102

Other languages

English (en)

Inventor

Odd Einar Ingvoldstad

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

2009-09-24 Priority claimed from US12/566,038 external-priority patent/US20110021833A1/en

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

2011-01-21 Publication of CA2710102A1 publication Critical patent/CA2710102A1/fr

Status Abandoned legal-status Critical Current

Links

238000002425 crystallisation Methods 0.000 title claims abstract description 22
230000008025 crystallization Effects 0.000 title claims abstract description 22
239000002872 contrast media Substances 0.000 title abstract description 7
230000002194 synthesizing effect Effects 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 38
238000000034 method Methods 0.000 claims abstract description 20
238000001728 nano-filtration Methods 0.000 claims abstract description 13
239000012452 mother liquor Substances 0.000 claims abstract description 11
239000012465 retentate Substances 0.000 claims abstract description 10
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 7
150000003839 salts Chemical class 0.000 claims abstract description 6
239000000725 suspension Substances 0.000 claims description 6
238000006192 iodination reaction Methods 0.000 claims description 4
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 3
239000012043 crude product Substances 0.000 claims description 3
230000007423 decrease Effects 0.000 claims description 3
239000012466 permeate Substances 0.000 claims description 3
239000012736 aqueous medium Substances 0.000 claims description 2
239000012336 iodinating agent Substances 0.000 claims description 2
239000013078 crystal Substances 0.000 abstract description 6
238000004519 manufacturing process Methods 0.000 abstract description 4
238000002360 preparation method Methods 0.000 abstract description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
239000000203 mixture Substances 0.000 description 6
239000012528 membrane Substances 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
239000012431 aqueous reaction media Substances 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
230000000052 comparative effect Effects 0.000 description 3
239000012065 filter cake Substances 0.000 description 3
238000001914 filtration Methods 0.000 description 3
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 3
239000004289 sodium hydrogen sulphite Substances 0.000 description 3
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 2
238000011026 diafiltration Methods 0.000 description 2
229960004359 iodixanol Drugs 0.000 description 2
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 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
239000013627 low molecular weight specie Substances 0.000 description 2
238000011084 recovery Methods 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
239000002002 slurry Substances 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
-1 2,3-dihydroxypropyl Chemical group 0.000 description 1
BHCBLTRDEYPMFZ-UHFFFAOYSA-N 5-acetamido-1-n,3-n-bis(2,3-dihydroxypropyl)-2,4,6-triiodobenzene-1,3-dicarboxamide Chemical compound CC(=O)NC1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I BHCBLTRDEYPMFZ-UHFFFAOYSA-N 0.000 description 1
NBDAHKQJXVLAID-UHFFFAOYSA-N 5-nitroisophthalic acid Chemical compound OC(=O)C1=CC(C(O)=O)=CC([N+]([O-])=O)=C1 NBDAHKQJXVLAID-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
229940126062 Compound A Drugs 0.000 description 1
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
239000008186 active pharmaceutical agent Substances 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000007806 chemical reaction intermediate Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000010586 diagram Methods 0.000 description 1
238000011038 discontinuous diafiltration by volume reduction Methods 0.000 description 1
229940126534 drug product Drugs 0.000 description 1
229940088679 drug related substance Drugs 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000009776 industrial production Methods 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229960001025 iohexol Drugs 0.000 description 1
229960000824 iopentol Drugs 0.000 description 1
238000011031 large-scale manufacturing process Methods 0.000 description 1
238000005457 optimization Methods 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
239000002699 waste material Substances 0.000 description 1

Landscapes

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

CA 2710102 2009-07-21 2010-07-20 Ameliorations de la cristallisation d'un intermediaire pour la synthese d'agents de contraste non ioniques pour rayons x Abandoned CA2710102A1 (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US22708409P	2009-07-21	2009-07-21
US61/227,084		2009-07-21
US12/566,038 US20110021833A1 (en)	2009-07-21	2009-09-24	Crystallization of an intermediate for synthesizing non-ionic x-ray contrast agents
US12/566,038		2009-09-24

Publications (1)

Publication Number	Publication Date
CA2710102A1 true CA2710102A1 (fr)	2011-01-21

Family

ID=43495937

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA 2710102 Abandoned CA2710102A1 (fr)	2009-07-21	2010-07-20	Ameliorations de la cristallisation d'un intermediaire pour la synthese d'agents de contraste non ioniques pour rayons x

Country Status (1)

Country	Link
CA (1)	CA2710102A1 (fr)

2010
- 2010-07-20 CA CA 2710102 patent/CA2710102A1/fr not_active Abandoned

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Legal Events

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