CA2084582A1 - Process for the production of mono-n-substituted tetraaza macrocycles - Google Patents

Process for the production of mono-n-substituted tetraaza macrocycles

Info

Publication number
CA2084582A1
CA2084582A1 CA002084582A CA2084582A CA2084582A1 CA 2084582 A1 CA2084582 A1 CA 2084582A1 CA 002084582 A CA002084582 A CA 002084582A CA 2084582 A CA2084582 A CA 2084582A CA 2084582 A1 CA2084582 A1 CA 2084582A1
Authority
CA
Canada
Prior art keywords
beta
optionally
tetraazacyclododecane
tetraazacyclotetradecane
formula
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.)
Granted
Application number
CA002084582A
Other languages
French (fr)
Other versions
CA2084582C (en
Inventor
Johannes Platzek
Heinz Gries
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.)
Bayer Pharma AG
Original Assignee
Johannes Platzek
Heinz Gries
Schering Aktiengesellschaft
Bayer Schering Pharma Aktiengesellschaft
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.)
Filing date
Publication date
Application filed by Johannes Platzek, Heinz Gries, Schering Aktiengesellschaft, Bayer Schering Pharma Aktiengesellschaft filed Critical Johannes Platzek
Publication of CA2084582A1 publication Critical patent/CA2084582A1/en
Application granted granted Critical
Publication of CA2084582C publication Critical patent/CA2084582C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • 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
    • C07D405/06—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 linked by a carbon chain containing only aliphatic carbon atoms
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

Process for the production of mono-N-substituted tetraazacyclododecane and tetraazacyclotetradecane derivatives of general formula I
(see formula I) in which n is 2 or 3, and R is .beta.-carboxylalkyl or .beta.-carboxylate alkyl, .beta.-cyanide alkyl, .beta.-carboxamidoalkyl, .beta.-hydroxyalkyl, aminocarbonyl, aminothiocarbonyl, .beta.-sulfamoylalkyl radical or a second tetraazacyclododecane or tetraazacyclotetradecane molecule bound by a bis(p-hydroxy)-alkylene chain, and wherein carboxyl and hydroxy groups are present optionally in protected form. The process comprises reacting a compound of general formula II
obtained from 1,4,7,10-tetraazacyclododecane or 1,4,8,11-tetraazacyclotetradecane (see formula II) with an .alpha.,.beta.-unsaturated ester, amide or nitrile, or an epoxide, isocyanate, isothiocyanate, aziridine or a bisepoxide, with or without solvent, at 0 to 220°C, within 1 to 48 hours, and optionally at a pressure up to 100 atm. The thus obtained reaction mixture, after cooling to -20°C to 80°C, is mixed with a mixture of water/organic solvent and stirred for 0.5 to 12 hours.
The thus formed (optionally to be isolated) intermediate products carrying a formyl group on a nitrogen atom are reacted by adding an inorganic base or an acid at 0 to 150°C, within 1 to 72, with stirring, optionally followed by subsequent removal of protecting groups, to obtain the end product of formula I, which can then be isolated preferably as the hydrochloride. The process provides improved yields of the product.
CA002084582A 1991-12-06 1992-12-04 Process for the production of mono-n-substituted tetraaza macrocycles Expired - Lifetime CA2084582C (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DEP4140779.2 1991-12-06
DE4140779A DE4140779A1 (en) 1991-12-06 1991-12-06 METHOD FOR PRODUCING MONO-N SUBSTITUTED TETRAAZAMACROCYCLES

Publications (2)

Publication Number Publication Date
CA2084582A1 true CA2084582A1 (en) 1993-06-07
CA2084582C CA2084582C (en) 2005-09-20

Family

ID=6446767

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002084582A Expired - Lifetime CA2084582C (en) 1991-12-06 1992-12-04 Process for the production of mono-n-substituted tetraaza macrocycles

Country Status (13)

Country Link
EP (1) EP0545511B1 (en)
JP (1) JP3471836B2 (en)
AT (1) ATE218131T1 (en)
CA (1) CA2084582C (en)
CZ (1) CZ290232B6 (en)
DE (2) DE4140779A1 (en)
DK (1) DK0545511T3 (en)
ES (1) ES2176183T3 (en)
HU (2) HU9203860D0 (en)
IL (1) IL103996A (en)
NO (5) NO303496B1 (en)
PT (1) PT545511E (en)
SK (1) SK282386B6 (en)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4237943C2 (en) * 1992-11-06 1997-10-23 Schering Ag Process for the preparation of metal complexes of N-beta-hydroxyalkyl-tri-N-carboxyalkyl-1,4,7,10-tetraazacyclododecane and N-beta-hydroxyalkyl-tri-N-carboxyalkyl-1,4,8,11-tetraazacyclotetradecane Derivatives
DE4317588C2 (en) * 1993-05-24 1998-04-16 Schering Ag Macrocyclic metal complexes containing fluorine, process for their preparation and their use
DE4318369C1 (en) * 1993-05-28 1995-02-09 Schering Ag Use of macrocyclic metal complexes as temperature probes
DE4340809C2 (en) * 1993-11-24 2000-08-03 Schering Ag 1.4,7,10-tetraazacyclododecane derivatives, pharmaceutical compositions containing them and process for their preparation
FR2725449B1 (en) * 1994-10-05 1996-12-27 Air Liquide POLYAZACYCLOALCANE DERIVATIVES, THEIR METAL COMPLEXES AND PHARMACEUTICAL PRODUCTS INCORPORATING THESE COMPLEXES
DE19724186C2 (en) * 1997-06-02 2002-07-18 Schering Ag Process for the mono- and 1,7-bis-N-ß-hydroxyalkylation of cycles and the corresponding N-ß-hydroxyalkyl-1,4,7,10-tetraazacyclododecane-Li salt complexes
IT1297035B1 (en) * 1997-12-30 1999-08-03 Bracco Spa 1,4,7,10-TETRAAZACICLODODECAN-1,4-DIACETIC ACID DERIVATIVES
DE19914101C1 (en) * 1999-03-22 2000-10-12 Schering Ag Perfluoroalkylamides, their preparation and their use in diagnostics
DE10002939C1 (en) * 2000-01-13 2001-09-20 Schering Ag New aromatic-substituted tetraazacyclododecane-triacetic acid paramagnetic metal complex compounds, are useful as contrast agents for magnetic resonance imaging of necrotic or infarction tissue
EP2608785B1 (en) * 2010-08-26 2016-08-17 Kunyuan Cui Lipomacrocycles and uses thereof
EA201600272A1 (en) 2011-04-21 2016-12-30 Байер Интеллектчуал Проперти Гмбх GETTING HADOBUTROL OF HIGH PURITY
KR101653064B1 (en) * 2014-12-26 2016-09-09 에스티팜 주식회사 A Method for Gadobutrol
KR102033964B1 (en) * 2018-01-19 2019-10-18 주식회사 엔지켐생명과학 Gadoteridol intermediate and method for preparing gadoteridol using the same

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3772785D1 (en) * 1986-01-23 1991-10-17 Squibb & Sons Inc 1-SUBSTITUTED-4,7,10-TRISCARBOXYMETHYL-1,4,7,10-TETRAAZACYCLODODECAN AND ANALOG.
DE3625417C2 (en) * 1986-07-28 1998-10-08 Schering Ag Tetraazacyclododecane derivatives
US4994560A (en) * 1987-06-24 1991-02-19 The Dow Chemical Company Functionalized polyamine chelants and radioactive rhodium complexes thereof for conjugation to antibodies
FR2644453A1 (en) * 1989-03-20 1990-09-21 Centre Nat Rech Scient PROCESS FOR THE PREPARATION OF MONOFUNCTIONALIZED CYCLIC TETRAMINES
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
NZ236267A (en) * 1989-12-22 1992-12-23 Squibb & Sons Inc 10-(2'-hydroxy-3'-polyoxaalkyl)-1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecane
DE4009119A1 (en) * 1990-03-19 1991-09-26 Schering Ag 1,4,7,10-TETRAAZACYCLODODECANE-BUTYLTRIOLS, METHOD FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL AGENTS CONTAINING THEM
DE4035760A1 (en) * 1990-11-08 1992-05-14 Schering Ag MONO-N-SUBSTITUTED 1,4,7,10-TETRAAZACYCLODODECAN DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL AGENTS CONTAINING THEM

Also Published As

Publication number Publication date
ES2176183T3 (en) 2002-12-01
NO973581D0 (en) 1997-08-04
NO924690L (en) 1993-06-07
IL103996A (en) 1998-02-08
DE59209957D1 (en) 2002-07-04
IL103996A0 (en) 1993-05-13
NO973579D0 (en) 1997-08-04
EP0545511B1 (en) 2002-05-29
NO303385B1 (en) 1998-07-06
JP3471836B2 (en) 2003-12-02
HU224923B1 (en) 2006-04-28
HUT65526A (en) 1994-06-28
CA2084582C (en) 2005-09-20
JPH05279349A (en) 1993-10-26
CZ290232B6 (en) 2002-06-12
NO973578L (en) 1993-06-07
NO303496B1 (en) 1998-07-20
NO303386B1 (en) 1998-07-06
NO303384B1 (en) 1998-07-06
NO924690D0 (en) 1992-12-04
ATE218131T1 (en) 2002-06-15
PT545511E (en) 2002-10-31
DE4140779A1 (en) 1993-06-09
NO973581L (en) 1993-06-07
SK282386B6 (en) 2002-01-07
NO973580L (en) 1993-06-07
NO973578D0 (en) 1997-08-04
SK357392A3 (en) 1993-08-11
DK0545511T3 (en) 2002-08-12
EP0545511A2 (en) 1993-06-09
NO973579L (en) 1993-06-07
HU9203860D0 (en) 1993-03-29
NO973580D0 (en) 1997-08-04
CZ357392A3 (en) 1993-08-11
NO303387B1 (en) 1998-07-06
EP0545511A3 (en) 1993-11-03

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Effective date: 20121204