2-(morpholin-4-yl)-1,7-naphthyridines

Patent metadata

Field	Value
Publication number	US-10772893-B2
Application number	US-201815974536-A
Country	US
Kind code	B2
Filing date	May 8, 2018
Priority date	Aug 4, 2014
Publication date	Sep 15, 2020
Grant date	Sep 15, 2020

Abstract

The present invention relates to substituted 2-(morpholin-4-yl)-1,7-naphthyridine compounds of general formula (I) or (Ib),

to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyperproliferative disease as a sole agent or in combination with other active ingredients.

First claim

The invention claimed is:

1. A compound of formula 5

wherein R 3 is hydrogen; and R 4 is hydrogen or methyl.

2. A process for preparing a compound of formula 5 according to claim 1 ,

wherein R 3 is hydrogen; and R 4 is hydrogen or methyl, comprising:
reacting a compound of formula 4 in an organic solvent with a strong base at a temperature between −20° C. and the organic solvent's boiling point to obtain the compound of formula 5.

3. The process according to claim 2 , in which wherein the strong base is lithium bis(trimethylsilyl)amide (LiHMDS), potassium bis(trimethylsilyl)amide (KHMDS), sodium bis(trimethylsilyl)amide (NaHMDS), or lithium diisopropylamide (LDA).

4. The process according to claim 2 , wherein the organic solvent is an aprotic organic solvent.

5. The process according to claim 4 , wherein the organic solvent is tetrahydrofuran or N,N-dimethylformamide.

6. The process according to claim 2 , wherein the compound of formula 4 is reacted in an organic solvent with a strong base at a temperature between −5° C. and 30° C. to obtain the compound of formula 5.

7. A compound of formula 11

wherein
R 1 is

wherein * indicates the point of attachment of said group with the rest of the molecule;

R 3 is hydrogen; and
R 4 is hydrogen or methyl.

8. A compound of formula 12

R 1 is

wherein * indicates the point of attachment of said group with the rest of the molecule;

R 3 is hydrogen;
R 4 is hydrogen or methyl; and
X is chloro, bromo or iodo.

9. A compound of formula 39

wherein Y is OH, —O—SO 2 —CF 3 , Cl, Br, I, SH, or SO 2 Cl.

10. A compound of formula 9

wherein R 3 is hydrogen; and R 4 is hydrogen or methyl.

11. A compound of formula 15

wherein
R 1 is

wherein * indicates the point of attachment of said group with the rest of the molecule;

R 3 is hydrogen; and
R 4 is hydrogen or methyl.

12. A compound of formula 16

wherein
R 1 is

wherein * indicates the point of attachment of said group with the rest of the molecule;

R 3 is hydrogen; and
R 4 is hydrogen or methyl.

Assignees

• Bayer Pharma AG

Inventors

• Wortmann Lars
• Lücking Ulrich
• Lefranc Julien
• Briem Hans
• Koppitz Marcus
• Eis Knut
• Von Nussbaum Franz
• Bader Benjamin
• Wengner Antje Margret
• Siemeister Gerhard
• Bone Wilhelm
• Lienau Philip
• Grudzinska-Goebel Joanna
• Moosmayer Dieter
• Eberspächer Uwe
• Schick Hans

Classifications

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• A61K31/5386

  spiro-condensed or forming part of bridged ring systems · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• A61K31/541 Primary

  Non-condensed thiazines containing further heterocyclic rings · CPC title