Transition metal mediated process

• US 20030109714A1
• Filed: 09/20/2002
• Published: 06/12/2003
• Est. Priority Date: 03/22/2001
• Status: Abandoned Application

• Current Assignee: Abbott GmbH & Company KG (Abbott Laboratories Incorporated)
• Original Assignee: Abbott GmbH & Company KG (Abbott Laboratories Incorporated)
• Inventors: Rudolph, Alena, Ritter, Kurt, Wishart, Neil
• Application Number:
  US10/251,562
• Publication Number:
  US 20030109714A1
• Time in Patent Office: Days
• US Class Current: 548/222
• CPC Class Codes: C07D 263/58 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links

Abstract

This invention relates to a transition metal mediated process for the preparation of optionally substituted 2-amino-benzoxazoles and or 2-amino-benzimidazoles, which are useful as therapeutic agents or as intermediates in the synthesis of therapeutic agents.

Claims

1. A method of making an optionally substituted 2-amino-benzoxazole or 2-amino-benzimidazole which comprises reacting a corresponding optionally substituted N-(2-hydroxyphenyl)thiourea or N-(2-aminophenyl)thiourea, respectively, with a transition metal in its I or II oxidation state, in the presence or absence of a base to obtain the optionally substituted 2-amino-benzoxazole or 2-aminobenzimidazole.

6. The process according to claim 1, 2, 4 or 5, wherein the transition metal is Cr, Mn, Fe, Co, Cu or Zn, or a combination thereof and wherein the base is selected from the group consisting of triethylamine, ammonia, sodium hydroxide, sodium hydrogen carbonate and cesium carbonate.

7. The process according to claim 6, wherein the transition metal is a corresponding salt or a combination of salts.

8. The process according to claim 6, wherein the transition metal is selected from the group consisting of copper (II) sulfate, anhydrous copper (II) sulfate or copper (I) chloride.

2. A process for the synthesis of a compound of formula (II),

3. A process for the synthesis of a compound of formula (II),

4. A process according to claim 3 wherein the isothiocyanate is of the formula R-NCS and the optionally substituted aniline is of the formula

5. A process for the synthesis of a compound of formula (II),

9. A method of making an optionally substituted 2-amino-benzoxazole or 2-amino-benzimidazole which comprises reacting a corresponding optionally substituted N-(2-hydroxyphenyl)thiourea or N-(2-aminophenyl)thiourea, respectively, with a transition metal in its III oxidation state, in the presence or absence of a base to obtain the optionally substituted 2-amino-benzoxazole or 2-aminobenzimidazole.

10. A process for the synthesis of a compound of formula (II),

14. The process according to claim 9, 10, 12, or 13, wherein the transition metal is Cr, Mn, Fe, or Co or a combination thereof and wherein the base is selected from the group consisting of triethylamine, ammonia, sodium hydroxide, sodium hydrogen carbonate and cesium carbonate.

15. The process according to claim 14, wherein the transition metal is a corresponding salt or a combination of salts.

16. The process according to claim 14, wherein the transition metal salt is selected from the group consisting of iron (III) chloride, anhydrous iron (III) chloride, manganese (III) acetate dihydrate and anhydrous manganese (III) diacetate.

11. A process for the synthesis of a compound of formula (II),

12. A process according to claim 11 wherein the isothiocyanate is of the formula R-NCS and the optionally substituted aniline is of the formula

13. A process for the synthesis of a compound of formula (II),