DIAZENE DIRECTED MODULAR SYNTHESIS OF COMPOUNDS WITH QUATERNARY CARBON CENTERS

• US 20190119286A1
• Filed: 10/15/2018
• Published: 04/25/2019
• Est. Priority Date: 10/13/2017
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Movassaghi, Mohammad, Lindovska, Petra
• Granted Patent: US 10,640,508 B2
• Time in Patent Office: Days
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

Diazene-directed modular synthesis is described for the preparation Csp2-Csp3 and Csp3-Csp3 linkages where one or more stereogenic quaternary carbon centers are formed. The disclosed methods are directed to the preparation of compounds of Formula (I), or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, from compounds of Formula (II):

wherein R¹-R⁵ and q are as defined independently for each occurrence herein. A wide variety of compounds can be accessed in this manner, including oligocyclotryptamines, where the stereochemistry of each subunit is beneficially secured before fragment coupling.

Claims

1. A method of preparing a compound of Formula (II′

);

2. The method of claim 1, wherein a compound of Formula (II′

), or a salt, tautomer, or stereoisomer thereof, is of the formula;

4. The method of claim 2, wherein a compound of Formula (IV′

-A), or a salt, tautomer, or stereoisomer thereof, is of the formula;

6. The method of claim 1, wherein the compound of Formula (III′

), or a salt, tautomer, or stereoisomer thereof, is of the formula;

7. The method of claim 6, wherein the compound of Formula (III′

), or a salt, tautomer, or stereoisomer thereof, is of the formula;

10. The method of claim 1, wherein the compound of Formula (III′

), or a salt, tautomer, or stereoisomer thereof, is of the formula;

11. The method of claim 1 further comprising reacting a compound of Formula (VI′

);

13. The method of claim 11 further comprising reacting a compound of Formula (VII′

);

14. The method of claim 13, wherein the compound of Formula (VIII′

), or a salt, tautomer, or stereoisomer thereof, is of the formula;

15. The method of claim 14, wherein the compound of Formula (VIII′

), or a salt, tautomer, or stereoisomer thereof, is of the formula;

16. The method of claim 13 further comprising reacting a compound of Formula (IX′

);

17. The method of claim 16 further comprising reacting a compound of Formula (X′

);

18. The method of claim 17, wherein the product of reacting a compound of Formula (X′

), or a salt, tautomer, or stereoisomer thereof, is a compound of the formula;

19. The method of claim 17, wherein the product of reacting a compound of Formula (X′

), or a salt, tautomer, or stereoisomer thereof, is a compound of the formula;

20. The method of claim 19, wherein the product of reacting a compound of Formula (X′

), or a salt, tautomer, or stereoisomer thereof, is of the formula;

21. The method of claim 1 further comprising reacting a compound of Formula (II′

);

22. The method of claim 21, wherein the product of reacting a compound of Formula (II′

), or a salt, tautomer, or stereoisomer thereof, is a compound of Formula (I′

);

23. The method of claim 22, wherein the compound of Formula (I′

), or a salt, tautomer, or stereoisomer thereof, is of the formula;

24. The method of claim 23, wherein the compound of Formula (I′

), or a salt, tautomer, or stereoisomer thereof, is;

37. The method of claim 21, wherein the product of reacting a compound of Formula (II′

), or a salt, tautomer, or stereoisomer thereof, is of the formula;

3. (canceled)

5. (canceled)

8-9. -9. (canceled)

12. (canceled)

25-36. -36. (canceled)