WO2000050385A1 - Process for the preparation of iopamidol - Google Patents
Process for the preparation of iopamidol Download PDFInfo
- Publication number
- WO2000050385A1 WO2000050385A1 PCT/US2000/004511 US0004511W WO0050385A1 WO 2000050385 A1 WO2000050385 A1 WO 2000050385A1 US 0004511 W US0004511 W US 0004511W WO 0050385 A1 WO0050385 A1 WO 0050385A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- process according
- group
- butyl
- propyl
- methyl
- Prior art date
Links
- 0 *NC(c(c(I)c(c(I)c1C(N*)=O)N)c1I)=O Chemical compound *NC(c(c(I)c(c(I)c1C(N*)=O)N)c1I)=O 0.000 description 1
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
Definitions
- the present invention relates to a process for the preparation of nonionic, water soluble compounds that are useful as contrast agents.
- lower alkyl groups include groups such as, for example, methyl, ethyl, n-propyl, /so-propyl, 2-methylpropyl /7-butyl, 2-butyl, f-butyl ⁇ -pentyl, 1-methylbutyl, 2,2-dimethylbutyl, 2-methylpentyl, 2,2-dimethylpropyl, and n-hexyl,.
- the preferred lower alkyl groups are methyl, ethyl, t7-propyl, /so-propyl, ⁇ -butyl, and f-butyl. More preferred are methyl and ethyl. Most preferred is methyl.
- the advantages of the present invention include reduction of racemization of the product and an improved method for isolation of the product. This provides a product with a higher enantiomeric excess (ee) than the methods disclosed in the documents discussed above.
- the process of the invention involves the deacylation of an ester of iopamidol using a catalytic amount of acid. The acid is removed by batch treatment with a small amount of an acid scavenging resin. Final purification involves passing an aqueous solution of the product through a column of non-ionic polymeric adsorbent resin, followed by concentration to an oil and recrystallization from acetonitrile/ethanol or ethanol alone. This process consistently produces material which meets all U.S. P. specifications including the optical rotation specification.
- Typical acid scavenging resins include weak basic resins such as , for example, IRA-68, IRA-67, Dowex® WGR-2, and the like. These resins remove any acid present.
- the tetraacetyl-diamide product is readily isolated by precipitation from water and further purification is generally not required.
- the tetraacetyl compound is treated with 2(S)-acetoxypropionyl chloride to provide a pentaacetyl-triamide.
- the acetate groups are removed by a transesterification reaction with hydrochloric acid in methanol to provide iopamidol.
- the acid is removed with an acid scavenging resin.
- Other impurities are removed using a polymer absorption resin.
- the product can be crystallized from ethanol or, optionally, if it contains excessive impurities, an acetonitrile/ethanol mixture.
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002364819A CA2364819C (en) | 1999-02-26 | 2000-02-23 | Process for the preparation of iopamidol |
AT00911908T ATE268749T1 (en) | 1999-02-26 | 2000-02-23 | METHOD FOR PRODUCING IOPAMIDOL |
DK00911908T DK1154986T3 (en) | 1999-02-26 | 2000-02-23 | Process for the preparation of iopamidol |
EP20000911908 EP1154986B1 (en) | 1999-02-26 | 2000-02-23 | Process for the preparation of iopamidol |
DE60011396T DE60011396T2 (en) | 1999-02-26 | 2000-02-23 | PROCESS FOR PREPARING IOPAMIDOL |
JP2000600969A JP4540233B2 (en) | 1999-02-26 | 2000-02-23 | Method for producing iopamidol |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/257,690 US6803485B2 (en) | 1999-02-26 | 1999-02-26 | Process for the preparation of iopamidol |
US09/257,690 | 1999-02-26 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000050385A1 true WO2000050385A1 (en) | 2000-08-31 |
Family
ID=22977346
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2000/004511 WO2000050385A1 (en) | 1999-02-26 | 2000-02-23 | Process for the preparation of iopamidol |
Country Status (10)
Country | Link |
---|---|
US (4) | US6803485B2 (en) |
EP (1) | EP1154986B1 (en) |
JP (1) | JP4540233B2 (en) |
AT (1) | ATE268749T1 (en) |
CA (1) | CA2364819C (en) |
DE (1) | DE60011396T2 (en) |
DK (1) | DK1154986T3 (en) |
ES (1) | ES2220429T3 (en) |
PT (1) | PT1154986E (en) |
WO (1) | WO2000050385A1 (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002044132A1 (en) * | 2000-12-01 | 2002-06-06 | Bracco Imaging S.P.A. | A process for the preparation of iopamidol and the new intermediates therein |
WO2003026702A1 (en) * | 2001-09-25 | 2003-04-03 | Upperton Limited | Particulate imaging contrast agents |
WO2012175903A1 (en) * | 2011-06-24 | 2012-12-27 | Hovione Inter. Ltd | Manufacture of a triiodinated contrast agent |
CN104098484A (en) * | 2014-07-21 | 2014-10-15 | 杭州杜易科技有限公司 | Iopamidol preparation method |
CN105017062A (en) * | 2014-04-18 | 2015-11-04 | 沈阳中海生物技术开发有限公司 | New method for preparing iopromide |
CN106831480A (en) * | 2015-12-07 | 2017-06-13 | 北京大学 | Contrast agent based on Iopamidol lipid derivate and preparation method thereof and purposes |
US9950991B2 (en) | 2013-11-05 | 2018-04-24 | Bracco Imaging S.P.A. | Process for the preparation of iopamidol |
KR20220139775A (en) | 2021-04-08 | 2022-10-17 | 한양대학교 에리카산학협력단 | Preparing method of iopamidol |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6803485B2 (en) * | 1999-02-26 | 2004-10-12 | Bracco Imaging S.P.A. | Process for the preparation of iopamidol |
US20040054162A1 (en) * | 2001-10-30 | 2004-03-18 | Hanna Michelle M. | Molecular detection systems utilizing reiterative oligonucleotide synthesis |
NO20055643D0 (en) * | 2005-11-29 | 2005-11-29 | Amersham Health As | Preparation of lodixanol |
US8907193B2 (en) * | 2007-02-20 | 2014-12-09 | Ubisoft Entertainment | Instrument game system and method |
JP2011509943A (en) | 2008-01-14 | 2011-03-31 | マリンクロッド・インコーポレイテッド | Process for preparing iosimenol |
US20110021824A1 (en) * | 2009-07-21 | 2011-01-27 | Ge Healthcare As | Adsorptive purification method for iodixanol |
WO2012136813A2 (en) | 2011-04-07 | 2012-10-11 | Universitetet I Oslo | Agents for medical radar diagnosis |
CN103382160B (en) * | 2012-05-02 | 2017-10-27 | 上海海神化学生物科技有限公司 | The synthesis of Iopamidol and its preparation of synthetic intermediate |
WO2019097242A1 (en) | 2017-11-16 | 2019-05-23 | Persica Pharmaceuticals Ltd. | Linezolid formulations |
CN115010617A (en) * | 2022-07-11 | 2022-09-06 | 安徽普利药业有限公司 | Preparation method of iopamidol |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4001323A (en) * | 1974-12-13 | 1977-01-04 | Savac Ag | Water-soluble, non-ionizing hydroxy-containing amide derivatives of 2,4,6-triiodo-isophthalic acid |
US4396598A (en) * | 1982-01-11 | 1983-08-02 | Mallinckrodt, Inc. | Triiodoisophthalamide X-ray contrast agent |
Family Cites Families (17)
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IT1193211B (en) | 1979-08-09 | 1988-06-15 | Bracco Ind Chimica Spa | 2,4,6-TRIIODE-ISOPHTHALIC ACID DERIVATIVES, METHOD FOR THEIR PREPARATION AND CONTRAST MEANS THAT CONTAIN THEM |
FR2541676A1 (en) | 1983-02-25 | 1984-08-31 | Guerbet Sa | NON-IONIC COMPOUNDS HAVING IOWED OR BROMINATED BENZENIC STRUCTURES AND OPACIFYING PRODUCTS CONTAINING SAME |
US4997983A (en) * | 1990-01-31 | 1991-03-05 | Mallinckrodt, Inc. | Process for production of ioversol |
US5204005A (en) | 1990-02-26 | 1993-04-20 | Mallinckrodt, Inc. | Reversed phase chromatographic process |
US5527926A (en) | 1990-11-26 | 1996-06-18 | Bracco International B.V. | Methods and compositions for using non-ionic contrast agents to reduce the risk of clot formation in diagnostic procedures |
IT1248741B (en) | 1991-02-26 | 1995-01-26 | Bracco Spa | CONCENTRATION AND PURIFICATION PROCESS OF ORGANIC COMPOUNDS |
US5256393A (en) | 1991-04-16 | 1993-10-26 | Mallinckrodt Medical, Inc. | Use of azeotropic distillation in process to dry 5-amino-N,N'bis (2,3-dihydroxypropyl)-2,4,6-triiodoisphthalamide |
CA2068089C (en) | 1991-05-31 | 2003-09-16 | Ramachandran S. Ranganathan | Method and compositions for using non-ionic contrast agents to reduce the risk of clot formulation in diagnostic procedures |
US5177261A (en) | 1991-07-22 | 1993-01-05 | Mallinckrodt Medical, Inc. | Synthesis of ioversol using chloroacetyl chloride |
IT1256162B (en) | 1992-10-27 | 1995-11-29 | Zambon Spa | PROCESS FOR THE PREPARATION OF AN INTERMEDIATE OF THE ORGANIC SYNTHESIS |
IT1256163B (en) | 1992-10-27 | 1995-11-29 | Zambon Spa | PROCESS FOR THE PREPARATION OF AN INTERMEDIATE OF THE ORGANIC SYNTHESIS |
US5396003A (en) * | 1993-05-27 | 1995-03-07 | Mallinckrodt Medical Pmc | Recovery and purification of 1,1,2-trichloroethane for reuse in the production of ioversol |
IL110391A (en) | 1993-07-30 | 1998-12-06 | Zambon Spa | Process for the crystallization of iopamidol |
IT1274027B (en) | 1994-03-03 | 1997-07-14 | Zambon Spa | PROCESS FOR THE PREPARATION AND PURIFICATION OF IODURATED CONTRAST MEANS |
US5371278A (en) | 1994-03-25 | 1994-12-06 | Mallinckrodt Medical Pmc | Synthesis of ioversol using a minimal excess of acetoxyacetylchloride |
IT1286522B1 (en) * | 1996-12-04 | 1998-07-15 | Dibra Spa | PROCESS FOR THE PREPARATION OF DERIVATIVES OF 5-AMINO-2,4,6- TRIIODO-1,3-BENZENEDICICARBOXYLIC ACID |
US6803485B2 (en) * | 1999-02-26 | 2004-10-12 | Bracco Imaging S.P.A. | Process for the preparation of iopamidol |
-
1999
- 1999-02-26 US US09/257,690 patent/US6803485B2/en not_active Expired - Lifetime
-
2000
- 2000-02-23 EP EP20000911908 patent/EP1154986B1/en not_active Expired - Lifetime
- 2000-02-23 ES ES00911908T patent/ES2220429T3/en not_active Expired - Lifetime
- 2000-02-23 WO PCT/US2000/004511 patent/WO2000050385A1/en active IP Right Grant
- 2000-02-23 DE DE60011396T patent/DE60011396T2/en not_active Expired - Lifetime
- 2000-02-23 DK DK00911908T patent/DK1154986T3/en active
- 2000-02-23 PT PT00911908T patent/PT1154986E/en unknown
- 2000-02-23 CA CA002364819A patent/CA2364819C/en not_active Expired - Lifetime
- 2000-02-23 AT AT00911908T patent/ATE268749T1/en active
- 2000-02-23 JP JP2000600969A patent/JP4540233B2/en not_active Expired - Lifetime
-
2004
- 2004-06-16 US US10/869,519 patent/US6875887B2/en not_active Expired - Lifetime
-
2005
- 2005-02-24 US US11/064,779 patent/US7115778B2/en not_active Expired - Lifetime
-
2006
- 2006-08-16 US US11/464,981 patent/US7282607B2/en not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4001323A (en) * | 1974-12-13 | 1977-01-04 | Savac Ag | Water-soluble, non-ionizing hydroxy-containing amide derivatives of 2,4,6-triiodo-isophthalic acid |
US4396598A (en) * | 1982-01-11 | 1983-08-02 | Mallinckrodt, Inc. | Triiodoisophthalamide X-ray contrast agent |
Cited By (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2975021A1 (en) | 2000-12-01 | 2016-01-20 | Bracco Imaging SPA | Process for the preparation of iopamidol |
US7034183B2 (en) | 2000-12-01 | 2006-04-25 | Bracco Imaging S.P.A. | Process for the preparation of iopamidol and the new intermediated therein |
CN100345821C (en) * | 2000-12-01 | 2007-10-31 | 布雷克成像有限公司 | Process for preparation of iopamidol and new intermediates therein |
US7368101B2 (en) | 2000-12-01 | 2008-05-06 | Bracco Imaging S.P.A. | Process for the preparation of iopamidol and the new intermediates therein |
KR100855765B1 (en) * | 2000-12-01 | 2008-09-01 | 브라코 이미징 에스.피.에이. | A Process for the Preparation of Iopamidol and the New Intermediates Therein |
CZ304015B6 (en) * | 2000-12-01 | 2013-08-21 | Bracco Imaging S. P. A. | Process for preparing iopamidol |
WO2002044132A1 (en) * | 2000-12-01 | 2002-06-06 | Bracco Imaging S.P.A. | A process for the preparation of iopamidol and the new intermediates therein |
WO2003026702A1 (en) * | 2001-09-25 | 2003-04-03 | Upperton Limited | Particulate imaging contrast agents |
WO2012175903A1 (en) * | 2011-06-24 | 2012-12-27 | Hovione Inter. Ltd | Manufacture of a triiodinated contrast agent |
CN103781758A (en) * | 2011-06-24 | 2014-05-07 | 霍维奥恩联合有限公司 | Manufacture of triiodinated contrast agent |
US8835672B2 (en) | 2011-06-24 | 2014-09-16 | Hovione Inter Limited | Manufacture of a triiodinated contrast agent |
CN107445858A (en) * | 2011-06-24 | 2017-12-08 | 霍维奥恩联合有限公司 | The production of triiodide contrast agent |
US9950991B2 (en) | 2013-11-05 | 2018-04-24 | Bracco Imaging S.P.A. | Process for the preparation of iopamidol |
EP3369724A1 (en) | 2013-11-05 | 2018-09-05 | Bracco Imaging SPA | Process for the preparation of iopamidol |
US10377700B2 (en) | 2013-11-05 | 2019-08-13 | Bracco Imaging S.P.A. | Process for the recovery of a boronic acid |
CN105017062A (en) * | 2014-04-18 | 2015-11-04 | 沈阳中海生物技术开发有限公司 | New method for preparing iopromide |
CN104098484A (en) * | 2014-07-21 | 2014-10-15 | 杭州杜易科技有限公司 | Iopamidol preparation method |
CN106831480A (en) * | 2015-12-07 | 2017-06-13 | 北京大学 | Contrast agent based on Iopamidol lipid derivate and preparation method thereof and purposes |
CN106831480B (en) * | 2015-12-07 | 2019-01-15 | 北京大学 | Contrast agent based on Iopamidol lipid derivate and preparation method thereof and purposes |
KR20220139775A (en) | 2021-04-08 | 2022-10-17 | 한양대학교 에리카산학협력단 | Preparing method of iopamidol |
Also Published As
Publication number | Publication date |
---|---|
ES2220429T3 (en) | 2004-12-16 |
US6803485B2 (en) | 2004-10-12 |
CA2364819C (en) | 2008-12-02 |
US20050192465A1 (en) | 2005-09-01 |
EP1154986A1 (en) | 2001-11-21 |
ATE268749T1 (en) | 2004-06-15 |
US7115778B2 (en) | 2006-10-03 |
US6875887B2 (en) | 2005-04-05 |
JP4540233B2 (en) | 2010-09-08 |
DE60011396D1 (en) | 2004-07-15 |
EP1154986B1 (en) | 2004-06-09 |
US7282607B2 (en) | 2007-10-16 |
DK1154986T3 (en) | 2004-10-18 |
US20040236150A1 (en) | 2004-11-25 |
US20010056206A1 (en) | 2001-12-27 |
CA2364819A1 (en) | 2000-08-31 |
US20070078281A1 (en) | 2007-04-05 |
JP2002537371A (en) | 2002-11-05 |
PT1154986E (en) | 2004-09-30 |
DE60011396T2 (en) | 2005-06-23 |
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