Electronically activated strained alkynes

Patent metadata

Field	Value
Publication number	US-10676449-B2
Application number	US-201916284258-A
Country	US
Kind code	B2
Filing date	Feb 25, 2019
Priority date	Jan 18, 2017
Publication date	Jun 9, 2020
Grant date	Jun 9, 2020

Abstract

Compounds of Formula I:

wherein:
R 1 and R 1′ are independently selected from hydrogen, halogen, C 1 -to-C 12 linear or branched hydroxyalkyl, C 1 -to-C 12 linear or branched halo-alkyl, carboxy, carboxyalkyl, amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, and N,N-dialkylcarbamoyloxy, provided that that R 1 and R 1′ are not simultaneously hydrogen; R 2 and R 2′ hydrogen, halogen, C 1 -to-C 12 linear or branched hydroxyalkyl, C 1 -to-C 12 linear or branched halo-alkyl, carboxy, carboxyalkyl, amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, and N,N-dialkylcarbamoyloxy, provided that that R 2 and R 2′ are not simultaneously hydrogen; R 3 is selected from hydrogen, C 1 to C 12 linear or branched alkyl, and nitrogen protecting groups; X is oxygen or nitrogen; when X is oxygen, R 4 is absent; and when X is nitrogen, R 4 is selected from H, C 1 -to-C 12 linear or branched alkyl, and nitrogen protecting groups.

First claim

What is claimed is:

1. A compound of Formula I:

wherein:
R 1 and R 1′ are independently selected from hydrogen, halogen, C 1 -to-C 12 linear or branched hydroxyalkyl, C 1 -to-C 12 linear or branched halo-alkyl, carboxy, carboxyalkyl, amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, and N,N-dialkylcarbamoyloxy, provided that that R 1 and R 1′ are not simultaneously hydrogen;
R 2 and R 2′ hydrogen, halogen, C 1 -to-C 12 linear or branched alkyl, C 1 -to-C 12 linear or branched hydroxyalkyl, C 1 -to-C 12 linear or branched halo-alkyl, carboxy, carboxyalkyl, amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, and N,N-dialkylcarbamoyloxy, provided that that R 2 and R 2′ are not simultaneously hydrogen;
R 3 is selected from hydrogen, C 1 to C 12 linear or branched alkyl, and nitrogen protecting groups;
X is oxygen or nitrogen;
when X is oxygen, R 4 is absent; and
when X is nitrogen, R 4 is selected from H, C 1 -to-C 12 linear or branched alkyl, and nitrogen protecting groups.

2. The compound of claim 1 , wherein X is oxygen.

3. The compound of claim 1 , wherein X is nitrogen.

4. The compound of claim 1 , wherein X is oxygen and at least one of R 1 or R 1′ is halogen.

5. The compound of claim 4 , wherein R 1 and R 1′ are halogen.

6. The compound of claim 4 , wherein at least one of R 1 and R 1′ are fluorine.

7. The compound of claim 4 , wherein R 1 and R 1′ are fluorine.

8. The compound of claim 4 , wherein at least one of R 2 and R 2′ is C 1 -to-C 12 linear or branched alkyl or C 1 -to-C 12 linear or branched hydroxyalkyl.

9. The compound of claim 4 , wherein at least one of R 2 and R 2′ is C 1 -to-C 12 linear or branched halo-alkyl.

10. The compound of claim 4 , wherein at least one of R 2 and R 2′ is carboxy or carboxyalkyl.

11. The compound of claim 4 , wherein at least one of R 2 and R 2′ is amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, or N,N-dialkylcarbamoyloxy.

12. The compound of claim 1 , wherein X is nitrogen and at least one of R 1 or R 1′ is halogen.

13. The compound of claim 12 , wherein R 1 and R 1′ are halogen.

14. The compound of claim 12 , wherein at least one of R 1 and R 1′ are fluorine.

15. The compound of claim 12 , wherein R 1 and R 1′ are fluorine.

16. The compound of claim 12 , wherein at least one of R 2 and R 2′ is C 1 -to-C 12 linear or branched alkyl or C 1 -to-C 12 linear or branched hydroxyalkyl.

17. The compound of claim 12 , wherein at least one of R 2 and R 2′ is C 1 -to-C 12 linear or branched halo-alkyl.

18. The compound of claim 12 , wherein at least one of R 2 and R 2′ is carboxy or carboxyalkyl.

19. The compound of claim 12 , wherein at least one of R 2 and R 2′ is amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, or N,N-dialkylcarbamoyloxy.

20. The compound of claim 12 , wherein R 4 is H.

21. The compound of claim 12 , wherein R 4 is C 1 -to-C 12 linear or branched alkyl.

22. Compounds of claim 12 , wherein R 4 is a nitrogen protecting group.

23. A method of forming chemical bonds, the method comprising reacting a first compound of Formula I:

wherein:
R 1 and R 1′ are independently selected from hydrogen, halogen, C 1 -to-C 12 linear or branched hydroxyalkyl, C 1 -to-C 12 linear or branched halo-alkyl, carboxy, carboxyalkyl, amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, and N,N-dialkylcarbamoyloxy, provided that that R 1 and R 1′ are not simultaneously hydrogen;
R 2 and R 2′ hydrogen, halogen, C 1 -to-C 12 linear or branched alkyl, C 1 -to-C 12 linear or branched hydroxyalkyl, C 1 -to-C 12 linear or branched halo-alkyl, carboxy, carboxyalkyl, amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, and N,N-dialkylcarbamoyloxy, provided that that R 2 and R 2′ are not simultaneously hydrogen;
R 3 is selected from hydrogen, C 1 to C 12 linear or branched alkyl, and nitrogen protecting groups;
X is oxygen or nitrogen;
when X is oxygen, R 4 is absent; and
when X is nitrogen, R 4 is selected from H, C 1 -to-C 12 linear or branched alkyl, and nitrogen protecting groups;
with a second compound comprising a 1,3-dipole, in a 1,3-cycloaddition reaction.

Assignees

• Wisconsin Alumni Res Found

Inventors

• Schomaker Jennifer M
• Burke Eileen G

Classifications

• C07D291/02 Primary

  not condensed with other rings · CPC title