Process for the production of dendritic trimesic acid triamides

• US 7,199,268 B2
• Filed: 12/16/2004
• Issued: 04/03/2007
• Est. Priority Date: 12/16/2003
• Status: Expired due to Fees

• Current Assignee: Bayer Schering Pharma AG (Bayer AG)
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Platzek, Johannes, Graske, Klaus-Dieter
• Primary Examiner(s): Kumar; Shailendra
• Application Number:
  US11/012,737
• Publication Number:
  US 20050238615A1
• Time in Patent Office: 838 Days
• Field of Search: 564/153, 564/133, 424/78.08
• US Class Current: 564/153
• CPC Class Codes: C07C 269/06 by reactions not involving the formation of carbamate groups
• CPC Class Codes: C07C 271/22 to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
• CPC Class Codes: C07K 7/02 Linear peptides containing at least one abnormal peptide link

Abstract

A new process for the production of dendritic trimesic acid triamides is described.

Claims

1. A process for the production of compounds of formula I

2. A process according to claim 1, wherein THF, 1-methyl-THF, tetrahydropyran, dichloromethane, 1,2-dimethoxyethane, dioxane, acetonitrile, propionitrile or chloroform is used as the non-protic solvent.

3. A process according to claim 1, wherein an organic base is used as the acid trap.

4. A process according to claim 1, wherein an inorganic base is used as the acid trap.

5. A process according to claim 3, wherein triethylamine, Hü

nig base, tributylamine, pyridine or lutidine is used as the acid trap.

6. A process according to claim 4, wherein sodium carbonate, potassium carbonate or lithium carbonate is used as the acid trap.

7. A process according to claim 1, wherein the operation is performed at a temperature of 50–

80°

C.

8. A process according to claim 1, wherein the reaction is performed within 0.5 to 2.5 hours.

10. The process of claim 1, further comprising cleaving the Z or Boc protective groups and converting the resulting amine to the Gadomer target compound by reaction with active esters of complexing agents.

11. The process of claim 1, wherein X in the formula II compounds is a Cl atom.

12. The process of claim 1, wherein the non-protic solvent is THF.

13. The process of claim 1, wherein the reaction is carried out at a temperature of from 50–

80°

C.

14. The process of claim 1, wherein the reaction is carried out for 30 minutes to 2.5 hours.

15. The process of claim 1, wherein R is a Z protective group.

16. The process of claim 1, wherein R is a Boc protective group.

17. The process of claim 1, further comprising purifying the crude product from the reaction by chromatography on normal or reversed-phase phases.

18. The process of claim 17, wherein the chromatography is a reversed-phase chromatography with a water-miscible mobile solvent.

19. The process of claim 18, wherein water-miscible solvent is selected from the group consisting of methanol, ethanol, acetonitrile, isopropanol, acetone and their mixtures with water.

20. The process of claim 18, further comprising isolating the product by spray-drying or by redistillation.

9. A compound of formula III: