Methods for forming protected organoboronic acids

Patent metadata

Field	Value
Publication number	US-9353131-B2
Application number	US-201314035408-A
Country	US
Kind code	B2
Filing date	Sep 24, 2013
Priority date	Feb 18, 2010
Publication date	May 31, 2016
Grant date	May 31, 2016

Abstract

Described are methods of forming protected boronic acids that provide in a manner that is straightforward, scalable, and cost-effective a wide variety of building blocks, such as building blocks containing complex and/or pharmaceutically important structures, and/or provide simple or complex protected organoboronic acid building blocks. A first method includes reacting an imino-di-carboxylic acid and an organoboronate salt. A second method includes reacting a N-substituted morpholine dione and an organoboronic acid.

First claim

What is claimed is:

1. A method of forming a protected boronic acid, comprising:
reacting in a reaction mixture
a N-substituted morpholine dione, and
an organoboronic acid represented by formula (XII):
R 1 —B(OH) 2   (XII),

wherein
R 1 is an organic group, and
the reaction mixture further comprises a polar aprotic solvent; and

thereby forming a protected organoboronic acid represented by formula (III) in the reaction mixture:

 where R 10 represents an organic group, and
R 11 , R 12 , R 13 and R 14 independently are selected from the group consisting of a hydrogen group and an organic group.

2. The method of claim 1 , wherein R 1 is an alkyl group, a heteroalkyl group, an alkenyl group, a heteroalkenyl group, an alkynyl group, a heteroalkynyl group, an aryl group, a heteroaryl group, or a combination of at least two of these groups.

3. The method of claim 1 , wherein R 1 is represented by formula (IV):
Y—R 5 —(R 6 ) m —  (IV),

wherein
Y is a halogen group or a pseudohalogen group;
R 5 is an aryl group or a heteroaryl group;
R 6 is an alkyl group, a heteroalkyl group, an alkenyl group, a heteroalkenyl group, an alkynyl group, a heteroalkynyl group, an aryl group, a heteroaryl group, or a combination of at least two of these groups; and
m is 0 or 1.

4. The method of claim 3 , wherein R 5 is a heteroaryl group.

5. The method of claim 1 , wherein R 1 is a heterocyclic group, an alkynyl group or an alkenyl group.

6. The method of claim 5 , wherein said heterocyclic group is selected from the group consisting of pyridine, indole, isoindole, indazole, purine, indolizidine, quinoline, isoquinoline, quinazoline, pteridine, quinolizidine, pyrrole, pyrazine, pyridazine, pyrimidine, imidazole, pyrasole, isoxazole, oxazole, thiazole, benzthiazole, furan, benzofuran, thiophene and benzothiophene.

7. The method of claim 1 , wherein R 1 is a 2-heterocyclic group selected from the group consisting of 2-pyridyl, 2-indolyl, 2-isoindolyl, 2-indazolyl, 2-purinyl, 2-indolizidinyl, 2-quinolinyl, 2-isoquinolinyl, 2-quinazolinyl, 2-pteridinyl, 2-quinolizidinyl, 2-pyrrolyl, 2-pyrazinyl, 2-pyridazinyl, 2-pyrimidinyl, 2-imidazolyl, 2-pyrasolyl, 2-isoxazolyl, 2-oxazolyl, 2-thiazolyl, 2-benzthiazolyl, 2-furyl, 2-benzofuryl, 2-thiophenyl, and 2-benzthiophenyl.

8. The method of claim 1 , wherein R 10 is methyl, and each of R 11 , R 12 , R 13 and R 14 is hydrogen.

9. The method of claim 1 , wherein the polar aprotic solvent is selected from the group consisting of tetrahydrofuran (THF), dioxane, acetonitrile, dimethyl formamide (DMF), toluene and xylene.

10. The method of claim 1 , wherein the polar aprotic solvent is THF.

11. The method of claim 1 , wherein the reaction mixture is maintained at a temperature of from 40° C. to 100° C.

Assignees

• Burke Martin D
• Dick Graham R
• Knapp David M
• Gillis Eric P
• Klubnick Jenna A
• Univ Illinois

Inventors

• Burke Martin D
• Dick Graham R
• Knapp David M
• Gillis Eric P
• Klubnick Jenna A

Classifications

• C07F5/025 Primary

  Boronic and borinic acid compounds · CPC title