Method for producing diarylpyridine derivatives

Patent metadata

Field	Value
Publication number	US-11999724-B2
Application number	US-201917252469-A
Country	US
Kind code	B2
Filing date	Jul 3, 2019
Priority date	Jul 4, 2018
Publication date	Jun 4, 2024
Grant date	Jun 4, 2024

Abstract

The present invention relates to a novel method for producing diarylpyridine derivatives, and the object of the present invention is to provide a novel, industrially useful method. The present inventors developed a novel method for synthesizing pyridine rings without using palladium, a strong base, or a high-temperature reaction. In particular, they successfully developed a method that can be used to synthesize iminium salts as intermediates, synthesize cyano compounds from these iminium salts, and cyclize the cyano compounds into pyridines under very mild reaction conditions.

First claim

The invention claimed is:

1. A production method comprising the step of reacting a compound represented by Formula (I):

with a chlorinating agent and dimethylformamide to obtain a compound represented by Formula (II):

or a salt thereof.

2. The method according to claim 1 , wherein the chlorinating agent is oxalyl chloride.

3. The method according to claim 1 , further comprising reacting the compound represented by Formula (II) or a salt thereof with a compound represented by Formula (III):

in the presence of a base to obtain a compound represented by Formula (IV):

or a salt thereof.

4. The method according to claim 3 , wherein the base is 2,6-lutidine.

5. The method according to claim 3 , further comprising reacting the compound represented by Formula (IV) or a salt thereof with benzylamine to obtain a compound represented by Formula (V):

or a salt thereof.

6. A production method comprising the steps of:
(i) reacting a compound represented by Formula (I′) with a Wittig reagent;

(ii) reacting the compound obtained in step (i) with a chlorinating agent and dimethylformamide;
(iii) reacting the compound obtained in step (ii) with a compound represented by Formula (III):

in the presence of a base; and
(iv) reacting the compound obtained in step (iii) with benzylamine to obtain a compound represented by Formula (V):

or a salt thereof.

7. The method according to claim 6 , wherein the Wittig reagent in step (i) is Ph 3 P(Cl)CH 2 OMe.

8. The method according to claim 6 , wherein the chlorinating agent in step (ii) is oxalyl chloride.

9. The method according to claim 6 , wherein the base in step (iii) is 2,6-lutidine.

10. The method according to claim 5 , further comprising reacting the compound represented by Formula (V) or salt thereof with hydrogen in a solvent and in the presence of a palladium on carbon catalyst to obtain a compound represented by Formula (VI):

or a salt thereof.

11. The method according to claim 10 , wherein the compound represented by Formula (V) or salt thereof is a hydrochloric acid salt of a compound represented by Formula (V), and the solvent is 1-propanol or N-methylpyrrolidone.

12. The method according to claim 10 , further comprising condensing the compound represented by Formula (VI) or salt thereof with a compound represented by Formula (VII):

or a salt thereof to obtain a compound represented by Formula (VIII):

or a salt thereof.

13. The method according to claim 12 , wherein the compound represented by Formula (VIII) or a salt thereof is a sulfuric acid salt of the compound represented by Formula (VIII).

14. A production method, comprising reacting a compound represented by Formula (VI):

or a salt thereof with a compound represented by Formula (VII):

or a salt thereof to obtain a compound represented by Formula (VIII):

or a salt thereof.

15. The method according to claim 14 , wherein the compound represented by Formula (VIII) or a salt thereof is a sulfuric acid salt of the compound represented by Formula (VIII).

16. The method according to claim 14 , further comprising reacting a compound represented by Formula (V) or a salt thereof:

with hydrogen in a solvent to obtain the compound represented by Formula (VI) or a salt thereof.

17. The method according to claim 16 , wherein the compound represented by Formula (V) or salt thereof is a hydrochloric acid salt of a compound represented by Formula (V), and the solvent is 1-propanol or N-methylpyrrolidone.

18. The method according to claim 16 , wherein reacting a compound represented by Formula (V) or a salt thereof with hydrogen is performed in the presence of a palladium on carbon catalyst.

Assignees

• Daiichi Sankyo Co Ltd

Inventors

• Aki Yuichi
• Toriyama Fumihiko
• SAKURAI Natsuki
• KAMEDA Ai
• Ogura Tomokazu

Classifications

• C07D405/14 Primary

  containing three or more hetero rings · CPC title

• B01J23/44

  Palladium · CPC title

• C07D319/12 Primary

  not condensed with other rings · CPC title

• C07D405/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07B61/00 Primary

  Other general methods · CPC title