Processes for forming amide bonds and compositions related thereto

Patent metadata

Field	Value
Publication number	US-9382193-B2
Application number	US-201414583850-A
Country	US
Kind code	B2
Filing date	Dec 29, 2014
Priority date	Oct 27, 2010
Publication date	Jul 5, 2016
Grant date	Jul 5, 2016

Abstract

The disclosure relates to methods for producing amide bonds and reagents related thereto. In some embodiments, the disclosure relates to methods of producing an amide comprising mixing an O-silylated thionoester and an amine under conditions such that an amide is formed. In another embodiment, the disclosure relates to mixing a thiolacid, a silylating agent, and an amine under conditions such that an amide is formed.

First claim

The invention claimed is:

1. A method of making a compound with an amide bond comprising mixing an O-silylated thionoester and a primary or secondary amine under conditions such that an amide is formed.

2. The method of claim 1 , wherein the method further comprises the step of providing the O-silylated thionoester by mixing a compound with a thiolacid group, and a silylating agent under conditions such that an O-silylated thionoester is formed.

3. The method of claim 2 , wherein the silylating agent is selected from the group consisting of trimethylsilanecarbonitrile, bis(trimethylsilyl)acetamide, and phenylchlorosilane.

4. The method of claim 2 , wherein the method further comprises the step of providing a compound with a thiolacid group by i) mixing a compound with a carboxylic acid group and a coupling reagent providing an activated carboxylic acid and ii) mixing the activated carboxylic acid and a thiol nucleophile providing a compound with at thiolacid group.

5. The method of claim 4 , wherein the coupling reagent is selected from the group consisting of dicyclohexylcarbodiimide or isopropyl chlorocarbonate.

6. The method of claim 4 , wherein the thiol nucleophile is selected from the group consisting of sodium hydrogen sulfide and trimethylsilyl thiol.

7. The method of claim 4 , wherein the compound with a carboxylic acid group is an amino acid.

8. The method of claim 1 , wherein the method further comprises the step of providing the O-silylated thionoester by mixing a compound with a carboxylic acid group, disulfide, and a phosphine under conditions such that an O-silylated thionoester is formed.

9. The method of claim 8 , wherein the disulfide is bis trimethylsilyl disulfide.

10. The method of claim 8 , wherein the compound with a carboxylic acid group is an amino acid.

Assignees

• Univ Emory

Inventors

• Liebeskind Lanny S
• Wu Wenting
• Zhang Zhihui
• Li Hao
• Lamar Angus A

Classifications

• C07D307/52

  Radicals substituted by nitrogen atoms not forming part of a nitro radical · CPC title

• C07K1/003

  by transforming the C-terminal amino acid to amides · CPC title

• C07D233/90

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07K5/06104

  with the first amino acid being acidic · CPC title

• C07K5/0812

  and aromatic or cycloaliphatic · CPC title