Process of making 3-phenylimino-3H-phenothiazine

• US 8,022,204 B2
• Filed: 12/09/2008
• Issued: 09/20/2011
• Est. Priority Date: 12/10/2007
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Marfurt, Karen L., Arndt, Henry C.
• Primary Examiner(s): HABTE, KAHSAY
• Application Number:
  US12/316,115
• Publication Number:
  US 20090171081A1
• Time in Patent Office: 1,015 Days
• Field of Search: 544/37
• US Class Current: 544/37
• CPC Class Codes: C07D 265/38 [b, e]-condensed with two six-membered rings
• CPC Class Codes: C07D 279/18 [b, e]-condensed with two six-membered rings
• CPC Class Codes: C07D 279/20 with hydrogen atoms directly attached to the ring nitrogen atom
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: G01N 27/3271 Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001

Abstract

A method of forming a 3-phenylimino-3H-phenothiazine or a 3-phenylimino-3H-phenoxazine mediator includes providing a first reactant including phenothiazine or phenoxazine, providing a first solvent, providing a second reactant and providing a second solvent. The first reactant, first solvent, second reactant and second solvent are combined to form a reactants solution. Sodium persulfate is added to the reactants solution to couple the first and second reactants resulting in a reaction solution including the 3-phenylimino-3H-phenothiazine or the 3-phenylimino-3H-phenoxazine mediator.

Claims

1. A method of forming a 3-phenylimino-3H-phenothiazine mediator, the method comprising the acts of:

providing a first reactant including phenothiazine;

providing a first solvent in which the phenothiazine has a desired solubility therein;

providing a second reactant to assist in forming the 3-phenylimino-3H-phenothiazine mediator;

providing a second solvent in which the second reactant has a desired solubility therein;

combining the first reactant, first solvent, second reactant and second solvent to form a reactants solution;

adding sodium persulfate to the reactants solution to couple the first and second reactants resulting in a reaction solution including the 3-phenylimino-3H-phenothiazine mediator; and

after adding the sodium persulfate, further processing to the reaction solution including the 3-phenylimino-3H-phenothiazine mediator so as to isolate the 3-phenylimino-3H-phenothiazine mediator.

2. The method of claim 1, wherein the first solvent includes tetrahydrofuran (THF).

3. The method of claim 1, wherein the second solvent includes water.

4. The method of claim 3, wherein the second solvent further includes sodium hydroxide.

5. The method of claim 1 wherein combining the first reactant, first solvent, second reactant and second solvent including the acts of combining the first reactant and the first solvent to form a first reactant solution, and combining the second reactant and the second solvent to form a second reactant solution before the first reactant, first solvent, second reactant and second solvent are combined together to form the reactants solution.

6. The method of claim 1, wherein further processing includes generally removing the second solvent by adding acetronitrile.

7. The method of claim 1, wherein further processing includes generally removing the first solvent by adding ethyl acetate.

8. The method of claim 1, wherein the second reactant includes aniline 2,5-disulfonic acid.

9. The method of claim 1, wherein the further processing includes substantially removing at least the first solvent and second solvent from the second solution so as to isolate the 3-phenylimino-3H-phenothiazine mediator.

10. The method of claim 1, wherein the 3-phenylimino-3H-phenothiazine mediator is in the form of a salt.

11. A method of forming and stabilizing a 3-phenylimino-3H-phenothiazine mediator, the method comprising the acts of:

providing a first reactant including phenothiazine;

providing a first solvent in which the phenothiazine has a desired solubility therein;

providing a second reactant to assist in forming the 3-phenylimino-3H-phenothiazine mediator;

providing a second solvent in which the second reactant has a desired solubility therein;

combining the first reactant, first solvent, second reactant and second solvent to form a reactants solution;

adding a coupling agent to the reactants solution to couple the first and second reactants resulting in a reaction solution including the 3-phenylimino-3H-phenothiazine mediator; and

after adding the coupling agent, further processing to the reaction solution including the 3-phenylimino-3H-phenothiazine mediator so as to isolate the 3-phenylimino-3H-phenothiazine mediator; and

stabilizing the 3-phenylimino-3H-phenothiazine mediator to a pH of from about 5 to about 8.

12. The method of claim 11, wherein the pH is from about 5.5 to about 7.

13. The method of claim 12, wherein the pH is from about 6 to about 7.

14. The method of claim 12, wherein the stabilizing the 3-phenylimino-3H-phenothiazine mediator includes adding sodium hydroxide, sodium bicarbonate, sodium phosphate, tetrabutylammonium hydroxide, calcium hydroxide, potassium hydroxide, potassium phosphate, potassium bicarbonate or combinations thereof.

15. The method of claim 11, wherein the first solvent includes tetrahydrofuran (THF).

16. The method of claim 11, wherein the second solvent includes water.

17. The method of claim 16, wherein the second solvent further includes sodium hydroxide.

18. The method of claim 11, wherein the second reactant includes aniline 2,5-disulfonic acid.