Mills T Kneller

6596904, Jul 22, 2003

Jan 29, 1996

08/593775

Thomas Jeffrey Dunn - Cedar Hill MO
David H. White - Ballwin MO
Mills Thomas Kneller - University City MO
Michelle M. Jones - Grover MO
Allan R. Bailey - Manchester MO

Mallinc Krodt Inc - St Louis MO

C07C23305

564153, 424 9454

The present invention discloses a new process for producing ioversol (marketed as OPTIRAYÂ) comprising: (a) reacting 5-amino-N,Nâ-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisopthalamide with chloroacetyl chloride in a polar aprotic solvent or combinations thereof to produce N,Nâ-bis[2,3-di(2-chloroacetoxy)propyl]-5-(2-chloroacetamido)-2,4,6-triiodoisophthalamide; (b) reacting the product of (a) with a base to produce N,Nâ-bis(2,3-dihydroxypropyl)-5-(2-chloroacetamido)-2,4,6-triiodoisopthalamide; (c) reacting the product of (b) with an alkylating agent capable of producing a hydroxyethylated product in the presence of a base and water to produce N,Nâ-bis(2,3-dihydroxypropyl)-5-[N-(2-hydroxyethyl) (2-chloroacetamido)]-2,4,6-triiodoisopthalamide; and (d) reacting the product of (c) in water and acetate ions to produce ioversol.

8445725, May 21, 2013

Jan 14, 2009

12/811833

Allan R. Bailey - Ballwin MO, US
Michelle M. Jones - O'fallon MO, US
Mills T. Kneller - University City MO, US
Alexander N. Petrov - St. Peters MO, US
David H. White - Ballwin MO, US
Oliver Egan - Meath, IE
Fiona Rooney - Monaghan, IE

Mallinckrodt LLC - Hazelwood MO

C07C 233/05

564153, 424 9452

A process for the preparation of iosimenol comprising reacting 5,5′-[(1,3-dioxo-1,3-propanediyl)diimino]bis[N-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide] (C-VI) with a 3-halo-1,2-propanediol in an aqueous solvent. A process for the preparation of C-VI comprising reacting 3,3′-[(1,3-dioxo-1,3-propanediyl)diimino]bis[5-(aminocarbonyl)-2,4,6-triiodobenzoyl chloride] (C-V) with 3-amino-1,2-propanediol in the presence of an inorganic base and a suitable non-aqueous polar solvent. A process for the preparation of C-V comprising reacting 3-amino-5-(aminocarbonyl)-2,4,6-triiodobenzoyl chloride (C-IV) with malonyl dichloride in a solvent comprising a suitable ester solvent, a suitable nitrile solvent or mixtures thereof.

20120184772, Jul 19, 2012

Sep 28, 2010

13/497318

Allan R. Bailey - Ballwin MO, US
Michelle M. Jones - O'Fallon MO, US
Mills T. Kneller - University City MO, US
Alexander N. Petrov - St. Peters MO, US
Michael A. Brown - O'Fallon MO, US
Benjamin J. Costello - Meath, IE

C07C 231/12

564153

The present disclosure is directed to a process for preparing an alkylated triiodo-substituted arylamide, such as iodixanol, the process comprising contacting a triiodo-substituted arylamide, such as 5-acetamido-N,N′-bis(2,3-dihydroxylpropyl)-2,4,6-triiodoisophthalamide, and an alkylating agent in the presence of a base and a mixed solvent system comprising a non-aqueous solvent and water, wherein the volume ratio of the non-aqueous solvent to water is greater than 1:1. The process advantageously enables the concentration of any impurities or undesirable byproduct from the reaction to be reduced, while increasing the yield of the desired reaction product.

20130261338, Oct 3, 2013

Feb 21, 2013

13/772572

Michelle M. Jones - Ofallon MO, US
Mills T. Kneller - University City MO, US
Alexander N. Petrov - St. Peters MO, US
David H. White - Ballwin MO, US
Oliver Egan - Meath, IE
Fiona Rooney - Monaghan, IE

Mallinckrodt LLC - Hazelwood MO

C07C 231/02

562853

A process for the preparation of iosimenol comprising reacting 5,5′-[(1,3-dioxo-1,3-propanediyl)diimino]bis[N-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide] (C-VI) with a 3-halo-1,2-propanediol in an aqueous solvent. A process for the preparation of C-VI comprising reacting 3,3′4(1,3-dioxo-1,3-propanediyl)diimino]bis[5-(aminocarbonyl)-2,4,6-triiodobenzoyl chloride] (C-V) with 3-amino-1,2-propanediol in the presence of an inorganic base and a suitable non-aqueous polar solvent. A process for the preparation of C-V comprising reacting 3-amino-5-(aminocarbonyl)-2,4,6-triiodobenzoyl chloride (C-IV) with malonyl dichloride in a solvent comprising a suitable ester solvent, a suitable nitrile solvent or mixtures thereof.

56485360, Jul 15, 1997

Jun 7, 1995

8/482380

Thomas Jeffrey Dunn - Cedar Hill MO
David H. White - Ballwin MO
Mills Thomas Kneller - University City MO
Michelle M. Jones - Grover MO
Narciso Ocampo Doran - Bridgeton MO

C07C23365
C07C23102

564153

The present invention discloses a new process for producing ioversol (marketed as OPTIRAY. RTM. ) comprising: (a) reacting 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisopthalamide with chloroacetyl chloride in a polar aprotic solvent, or combinations thereof, to produce N,N'-bis[2,3-di(2-chloroacetoxy)propyl]-5-(2-chloroacetamido)-2,4,6-triiod oisophthalamide; (b) reacting the product of (a) with sodium hydroxide to produce N,N'-bis(2,3-dihydroxypropyl)-5-(2-chloroacetamido)-2,4,6-triiodoisopthala mide; (c) reacting the product of (b) in water and sodium acetate to produce N,N'-bis(2,3-dihydroxypropyl)-5-glycolamido-2,4,6-triiodoisopthalamide; and (d) reacting the product of (c) with an alkylating agent capable of producing hydroxylhylated product in the presence of a base and water to produce ioversol.

52040054, Apr 20, 1993

Jan 28, 1991

7/646836

Narciso O. Doran - Bridgeton MO
Thomas J. Dunn - Cedar Hill MO
Mills T. Kneller - University City MO
Youlin Lin - Chesterfield MO
David H. White - Florissant MO
David Ming-Lee Wong - Chesterfield MO

Mallinckrodt, Inc. - St. Louis MO

B01D 1508

210656

An improved process for the reversed phase chromatographic decolorization, separation, and purification of water-soluble, nonionic contrast media compounds from solutions containing nonionic compound impurities involves the steps of (a) packing a chromatographic column with a chromatographic packing material; (b) passing through the column a solution containing a water-soluble, nonionic contrast media compound and nonionic compounds as impurities at a loading ratio between approximately 10 to 1 and 1. 5 to 1 wt. packing material/total wt. nonionic compounds; and (c) eluting the column to produce an eluate containing substantially pure, water-soluble, nonionic contrast media compound or MRI agent. The process can be economically practiced on a factory scale and efficiently removes non-polar impurities difficult to remove by conventional methods.

40667430, Jan 3, 1978

Jun 21, 1976

5/697999

Mills T. Kneller - University City MO

Mallinckrodt, Inc. - St. Louis MO

C07D26314
A61K 2902

424 5

3-Acetamido-5-(4,4-bishydroxymethyl-2-oxazolinyl)-2,4,6-triiodobenzoic acid, 3-acetamido-5-(4-methyl-4-hydroxymethyl-2-oxazolinyl)-2,4,6-triiodob enzoic acid, analogous compounds and salts and esters thereof are useful as X-ray contrast agents. The corresponding acyl halides are useful as intermediates.

53712781, Dec 6, 1994

Mar 25, 1994

8/217575

William Z. McCarthy - St. Louis MO
Mills T. Kneller - University City MO
Youlin Lin - Chesterfield MO
Rebecca A. Wallace - Manchester MO
David H. White - Ballwin MO

Mallinckrodt Medical PMC - Las Vegas NV

C07C 6702

560251

The use of a minimal excess of acetoxyacetylchloride as a reagent in the synthesis of N,N'-bis(2,3-dihydroxypropyl)-5-N-(2-hydroxy-ethyl)glycolamido-2,4,6-triio doisophthalamide.