(Di)amination of activated allene compounds, derivatives thereof, and methods for synthesis of the same

Patent metadata

Field	Value
Publication number	US-12180182-B2
Application number	US-202218060922-A
Country	US
Kind code	B2
Filing date	Dec 1, 2022
Priority date	Dec 1, 2021
Publication date	Dec 31, 2024
Grant date	Dec 31, 2024

Abstract

One-pot synthesis methods for producing amines from activated allenes and derivatives thereof are provided, as well as the compounds produced thereby.

First claim

The invention claimed is:

1. A method of synthesizing amines from activated allene compounds or derivatives thereof in a one-pot reaction comprising:
providing a solution comprising an electrophilic amine or an allene and an amine halogenating reagent and adding a first compound to the solution to carry out a first animation reaction, wherein the first compound comprises an electron-withdrawing group (EWG);
adding a nucleophilic reagent and a base to a reaction mixture of the animation reaction to carry out a second nucleophilic reaction; and
adding a reducing reagent to a reaction mixture of the nucleophilic reaction to carry out a third enamine reduction reaction and synthesize an amine product from an activated allene compound or derivative thereof;
wherein the amine product has a structure of Formula (III) or is a pharmaceutically acceptable salt thereof:

wherein:
X is an N containing cyclic group;
R 1 is D or absent;
R 2 is

wherein Y is N, S, C, or O, and

comprises the EWG, wherein R 3 is OBn, OEt,

Xa is an N-containing cyclic group; and
X 1 is absent or F.

2. The method of claim 1 , wherein the amine halogenating reagent comprises one or more of t-BuOCl, tetra-n-butylammonium iodide (TBAI), N-bromosuccinimide (NBS), N-Iodosuccinimide (NIS), N-Chlorosuccinimide (NCS), KI, and NaI.

3. The method of claim 2 , wherein the amine halogenating reagent comprises a mixture of t-BuOCl and TBAI.

4. The method of claim 1 , wherein the electrophilic amine is a cyclic aliphatic amine.

5. The method of claim 1 , wherein the electrophilic amine has a structure of the formula R 3 R 4 NH, wherein R 3 and R 4 are each independently an optionally substituted C 3 -C 10 cycloalkyl, C 3 -C 10 hetero cyclic ring, C 5 -C 12 aryl, or C 5 -C 12 heteroaryl.

6. The method of claim 5 , wherein the first compound has a structure of Formula I:

wherein:
R 1 is H or F; and
R 2 is the EWG.

7. The method of claim 1 , wherein the nucleophilic reagent is a cyclic amine, an acyclic amine, an imide, or a sulfonamide.

8. The method of claim 7 , wherein the nucleophilic reagent has a structure of the formula HNR 6 R 7 or HXR 8 , wherein:
X is O or S; and
R 6 , R 7 and R 8 are each independently an optionally substituted C 1 -C 12 straight or branched alkyl, C 2 -C 12 straight or branched alkenyl, C 2 -C 12 straight or branched alkynyl, C 3 -C 10 cycloalkyl, C 3 -C 10 hetero cyclic ring, C 5 -C 12 aryl, or C 5 -C 12 heteroaryl.

9. The method of claim 8 , wherein R 6 and R 7 are joined together to form an optionally substituted heterocyclic ring.

10. The method of claim 1 , wherein the base is ceasium carbonate (Cs 2 CO 3 ), potassium carbonate (K 2 CO 3 ) or tetrahydrofuran (THF).

11. The method of claim 1 , wherein the reducing agent comprises NaBH 3 CN.

12. The method of claim 11 , further comprising adding a co-solvent of MeOH/AcOH to a reaction mixture of the reduction reaction.

13. The method of claim 1 , further comprising drying and purifying the activated allene compound or derivative thereof.

Assignees

• Purdue Research Foundation

Inventors

• Dai Mingji

Classifications

• C07D403/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D333/34

  Sulfur atoms · CPC title

• C07D311/16

  substituted in position 7 · CPC title

• C07J43/003

  not condensed · CPC title

• C07D263/56

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2 · CPC title