Intermediates for preparing triazole agonists of the APJ receptor

Patent metadata

Field	Value
Publication number	US-9845310-B2
Application number	US-201615298748-A
Country	US
Kind code	B2
Filing date	Oct 20, 2016
Priority date	May 20, 2015
Publication date	Dec 19, 2017
Grant date	Dec 19, 2017

Abstract

Compounds of Formula VII, salts thereof, tautomers thereof, and salts of the tautomers are useful intermediates in the synthesis of agonists of the APJ Receptor. Compounds of Formula VII have the following structure:

where the definitions of the variables are provided herein.

First claim

What is claimed:

1. A compound of Formula VII, a salt thereof, a tautomer thereof, or a salt of the tautomer:

wherein:
R 3e′ is a —C 1 -C 6 alkyl;
R 3g′ is selected from —C 1 -C 6 alkyl, —C 1 -C 6 haloalkyl, —C 1 -C 6 perhaloalkyl, —OH, —O—(C 1 -C 6 alkyl), —O—(C 1 -C 6 haloalkyl), —O—(C 1 -C 6 perhaloalkyl), —O—(C 1 -C 6 alkyl)-OH, or —O—(C 1 -C 6 alkyl)-O—(C 1 -C 6 alkyl);
Q′ is a monocyclic 6-membered heteroaryl group with 1, 2, or 3 N heteroatoms, wherein the heteroaryl group is unsubstituted or is substituted with 1, 2, 3, or 4 R Q′ substituent; and
R Q′ in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C 1 -C 6 alkyl, —C 1 -C 6 haloalkyl, —C 1 -C 6 perhaloalkyl, —C 2 -C 6 alkenyl, —C 2 -C 6 alkynyl, —OH, —O—(C 1 -C 6 alkyl), —O—(C 1 -C 6 haloalkyl), —O—(C 1 -C 6 perhaloalkyl), —NH 2 , —NH(C 1 -C 6 alkyl), —N(C 1 -C 6 alkyl) 2 , —C(═O)—(C 1 -C 6 alkyl), —C(═O)OH, —C(═O)—O—(C 1 -C 6 alkyl), —C(═O)NH 2 , —C(═O)NH(C 1 -C 6 alkyl), —C(═O)N(C 1 -C 6 alkyl) 2 , or —S(═O) 2 —(C 1 -C 6 alkyl).

2. The compound of claim 1 , the salt thereof, the tautomer thereof, or the salt of the tautomer, wherein Q′ is selected from a pyridinyl, pyrimidinyl, or pyrazinyl group that is unsubstituted or is substituted with 1, or 2 R Q′ substituents.

3. The compound of claim 1 , the salt thereof, the tautomer thereof, or the salt of the tautomer, wherein Q′ is selected from

wherein the symbol , when drawn across a bond, indicates the point of attachment to the rest of the molecule.

4. The compound of claim 1 , the salt thereof, the tautomer thereof, or the salt of the tautomer, wherein Q′ is selected from

wherein the symbol , when drawn across a bond, indicates the point of attachment to the rest of the molecule.

5. The compound of claim 4 , the salt thereof, the tautomer thereof, or the salt of the tautomer, wherein R 3e′ is a —CH 3 .

6. The compound of claim 5 , the salt thereof, the tautomer thereof, or the salt of the tautomer, wherein R 3g′ is a —C 1 -C 6 alkyl.

7. The compound of claim 6 , the salt thereof, the tautomer thereof, or the salt of the tautomer, wherein R 3g′ is a —CH 3 .

8. The compound of claim 5 , the salt thereof, the tautomer thereof, or the salt of the tautomer, wherein R 3g′ is a —O—(C 1 -C 6 alkyl).

9. The compound of claim 8 , the salt thereof, the tautomer thereof, or the salt of the tautomer, wherein R 3g′ is selected from —O—CH 3 , —O—CH 2 CH 3 , or —O—CH(CH 3 ) 2 .

10. The compound of claim 1 , the salt thereof, the tautomer thereof, or the salt of the tautomer, wherein R 3e′ is a —CH 3 .

11. The compound of claim 1 , the salt thereof, the tautomer thereof, or the salt of the tautomer, wherein R 3g′ is a —C 1 -C 6 alkyl.

12. The compound of claim ll, the salt thereof, the tautomer thereof, or the salt of the tautomer, wherein R 3g′ is a —CH 3 .

13. The compound of claim 1 , the salt thereof, the tautomer thereof, or the salt of the tautomer, wherein R 3g′ is a —O—(C 1 -C 6 alkyl).

14. The compound of claim 13 , the salt thereof, the tautomer thereof, or the salt of the tautomer, wherein R 3g′ is selected from —O —CH 3 , —O—CH 2 CH 3 , or —O—CH(CH 3 ) 2 .

15. The compound of claim 1 , the salt thereof, the tautomer thereof, or the salt of the tautomer, wherein the compound is selected from

16. The compound of claim 15 , the salt thereof, the tautomer thereof, or the salt of the tautomer, wherein Q′ is selected from

wherein the symbol , when drawn across a bond, indicates the point of attachment to the rest of the molecule.

Assignees

• Amgen Inc

Inventors

• Chen Ning
• Chen Xiaoqi
• Cheng Alan C
• Connors Richard V
• Deignan Jeffrey
• Dransfield Paul John
• Du Xiaohui
• Fu Zice
• Heath Julie Anne
• Horne Daniel B
• Houze Jonathan
• Kaller Matthew R
• Kopecky David John
• Lai Su-Jen
• Ma Zhihua
• Mcgee Lawrence R
• Medina Julio C
• Mihalic Jeffrey T
• Nishimura Nobuko
• Olson Steven H
• Pattaropong Vatee
• Wang Xiaodong
• Yang Kevin
• Debenedetto Mikkel V
• Hedley Simon J

Classifications

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P9/12

  Antihypertensives · CPC title

• C07D211/54

  Sulfur atoms · CPC title

• A61K31/497

  containing further heterocyclic rings · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title