IP Library › Granted Patent US 12,264,135
Granted Patent B2
US 12,264,135 · App. 18/225,537 · Granted Apr 1, 2025

Synthesis of 1,4-diazaspiro[5.5]undecan-3-one

Inventors: Stephen E. Schneider (Raleigh, NC); Hannah White (Chapel Hill, NC); Thomas Fessard (Basel, CH); Sagar Beldar (Basel, CH)
Assignee: Pharmacosmos Holding A/S
C07D241/38C07C219/18C07D239/47
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Quick Facts
Patent No.
US 12,264,135
App. No.
18/225,537
Granted
Apr 1, 2025
Kind
B2
Abstract

This invention provides a process for preparing 1,4-diazaspiro[5.5]undecan-3-one and analogues thereof that are useful in the preparation of pharmaceutical compound, including for the treatment of disorders involving abnormal cellular proliferation. Chemical intermediates in the process are also provided.

Claims (34)

1. A process to prepare a spirocyclic compound comprising:

a. reducing a compound of Formula III with a reducing agent;

b. cyclizing the compound of step (a);

wherein Formula III is:

wherein the spirocyclic compound is of Formula:

wherein

y is 0;

n is 0 or 1;

R 1 is hydrogen;

R 2 is hydrogen, substituted heteroaryl, or

R 3 is hydrogen;

R 4 is NR 8 R 9 or OR 10 ;

R 8 and R 9 are independently selected from the group consisting of hydrogen, alkyl, aryl, and -alkyl-aryl;

R 10 is alkyl, aryl, or -alkyl-aryl;

R 12 is alkyl, aryl, or -alkyl-aryl; and

R 13 is —S-alkyl or Cl.

2. The process of claim 1 , wherein the reducing agent is zinc.

3. The process of claim 2 , wherein an acidic additive is used with the reducing agent.

4. The process of claim 3 , wherein the acidic additive is ammonium chloride.

5. The process of claim 1 , wherein the reducing agent is platinum(IV) oxide in the presence of hydrogen gas.

6. The process of claim 1 , wherein the reducing agent is Raney nickel in the presence of hydrogen gas.

7. The process of claim 1 , wherein the reducing agent is iron.

8. The process of claim 1 , wherein the reducing agent is samarium diiodide.

9. The process of claim 1 , wherein the reduction and cyclization occur in the same reaction vessel.

10. The process of claim 1 , wherein water is a solvent used in the reduction step.

11. The process of claim 1 , wherein a mixture of water and acetone is used as the solvent in the reduction step.

12. The process of claim 1 , wherein the reduction and cyclization is conducted at about 25° C.

13. The process of claim 1 , wherein the reduction and cyclization is conducted at about 15° C.

14. The process of claim 1 , wherein the reduction and cyclization is conducted at about 35° C.

15. The process of claim 1 , wherein the cyclization is acid catalyzed.

16. The process of claim 1 , wherein the cyclization is base catalyzed.

17. The process of claim 1 , wherein R 4 is —OMe or —OEt.

18. The process of claim 1 , wherein the spirocyclic compound is:

and wherein the compound of Formula III is:

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 5, 2024
From: G1 THERAPEUTICS, INC.
To: PHARMACOSMOS A/S
Reel/Frame 069502/0159 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 5, 2024
From: PHARMACOSMOS A/S
To: PHARMACOSMOS HOLDING A/S
Reel/Frame 069502/0179 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 6, 2024
From: SCHNEIDER, STEPHEN; WHITE, HANNAH
To: G1 THERAPEUTICS, INC.
Reel/Frame 067325/0666 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 6, 2024
From: FESSARD, THOMAS; BELDAR, SAGAR
To: SPIROCHEM AG
Reel/Frame 067325/0721 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 6, 2024
From: SPIROCHEM AG
To: G1 THERAPEUTICS, INC.
Reel/Frame 067325/0729 →
Continuity (4)
Continuation 17184354 · Feb 24, 2021
Continuation PCTUS2019048029 · Aug 23, 2019
Provisional Application 62722675 · Aug 24, 2018
Related Publication 20240199556A1 · Jun 20, 2024
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