Treatment of androgen deprivation therapy associated symptoms

Patent metadata

Field	Value
Publication number	US-10799478-B2
Application number	US-201816216256-A
Country	US
Kind code	B2
Filing date	Dec 11, 2018
Priority date	Sep 11, 2014
Publication date	Oct 13, 2020
Grant date	Oct 13, 2020

Abstract

The present invention provides a method of treating symptoms associated with Androgen Deprivation Therapy comprising administering to a patient in need of such treatment an effective amount of a compound of Formula I:

or a pharmaceutically acceptable salt thereof.

First claim

What is claimed is:

1. A process for the preparation of the compound of Formula I

comprising the steps of:
(a) reacting Zn(CN) 2 with the compound of Formula II, thereby forming the compound of Formula III

(b) forming the compound of Formula I by reacting the compound of Formula III with the compound of Formula IV

2. The process of claim 1 , wherein the reaction of the compound of Formula II with Zn(CN) 2 to form a compound of Formula III comprises:
(i) reacting the compound of Formula II with Zn(CN) 2 , Zn(OAc) 2 , Zn, and Pd(dppf) 2 Cl 2 .CH 2 Cl 2 in DMAc to form a compound of Formula III in solution;
(ii) adding water to precipitate and isolate the compound of Formula III from the solution;
(iii) dissolving the precipitated isolate of the compound of Formula III in a mixture of MTBE and acetone to form a slurry;
(iv) filtering the slurry to form a filtrate having a compound of Formula III; and
(v) treating the filtrate having a compound of Formula III with charcoal, MgSO 4 , and FLORISIL™.

3. The process of claim 2 , wherein the compound of Formula III is crystalized in the heptane.

4. The process of claim 1 , wherein a substantially pure form of a compound of Formula I is produced by a process which comprises the steps of:
(i) reacting the compound of Formula III with 2-picolyl chloride hydrochloride and K 2 CO 3 in DMAC to give a compound of Formula I in solution; and
(ii) isolating the compound of Formula I by adding water to the solution formed in step (i) and filtering.

5. The process of claim 4 , additionally comprising the further step of:
(iii) recrystallizing the filtered isolate in EtOH to produce a substantially pure crystalline form of a compound of Formula I.

6. The process of claim 5 , wherein the filtered isolate is recrystallized at least three times in EtOH to produce a substantially pure crystalline form of a compound of Formula I.

7. The process of claim 6 , wherein said substantially pure crystalline form of a compound of Formula I comprises less than 15% by weight of impurities.

Assignees

• Lilly Co Eli

Inventors

• Richey Rachel Nicole
• Yu Hannah

Classifications

• A61K31/4439 Primary

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• A61K31/403 Primary

  condensed with carbocyclic rings, e.g. carbazole · CPC title

• C07D401/06 Primary

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title