Intermediate compound of novel tetrahydronaphthyl urea derivative

Patent metadata

Field	Value
Publication number	US-10927079-B2
Application number	US-202016849528-A
Country	US
Kind code	B2
Filing date	Apr 15, 2020
Priority date	Apr 27, 2017
Publication date	Feb 23, 2021
Grant date	Feb 23, 2021

Abstract

An intermediate compound, a pharmaceutically acceptable salt thereof, or a solvate thereof is disclosed wherein the intermediate compound is represented by formula (AM-2-RR)⋅(D-TA):

in which p represents an integer of 0 to 4; R 1 each independently represent a halogen atom, a cyano group, a C 1-6 alkyl group, a halogenated C 1-6 alkyl group, a hydroxy C 1-6 alkyl group, a cyanated C 1-6 alkyl group, a halogenated C 1-6 alkoxy group, a C 1-6 alkoxy C 1-6 alkyl group, a mono-/di-C 2-7 alkanoyl amino group, a carboxamide group, or a C 1-6 alkoxy carbonyl group; and R 2a and R 2b each independently represent a C 1-6 alkyl group.

First claim

What is claimed is:

1. An intermediate compound, a pharmaceutically acceptable salt thereof, or a solvate thereof, the intermediate compound represented by formula (AM-2-RR)⋅(D-TA):

in which
p represents an integer of 0 to 4;
R 1 each independently represent a halogen atom, a cyano group, a C 1-6 alkyl group, a halogenated C 1-6 alkyl group, a hydroxy C 1-6 alkyl group, a cyanated C 1-6 alkyl group, a halogenated C 1-6 alkoxy group, a C 1-6 alkoxy C 1-6 alkyl group, a mono-/di-C 2-7 alkanoyl amino group, a —C(═O)NH 2 group, or a C 1-6 alkoxy carbonyl group; and
R 2a and R 2b each independently represent a C 1-6 alkyl group.

2. The intermediate compound, the pharmaceutically acceptable salt thereof, or the solvate thereof according to claim 1 , wherein: p represents an integer 0.

3. The intermediate compound, the pharmaceutically acceptable salt thereof, or the solvate thereof according to claim 1 , wherein: R 2a and R 2b each represent methyl group.

4. The intermediate compound, the pharmaceutically acceptable salt thereof, or the solvate thereof according to claim 1 , wherein: p represents an integer 0, and R 2a and R 2b each represent methyl group.

5. The intermediate compound, the pharmaceutically acceptable salt thereof, or the solvate thereof according to claim 1 , the intermediate compound represented by formula (AM-2a-RR)⋅(D-TA):

in which
R 1a and R 1b each independently represent a hydrogen atom, a halogen atom, a cyano group, a C 1-6 alkyl group, a halogenated C 1-6 alkyl group, a hydroxy C 1-6 alkyl group, a cyanated C 1-6 alkyl group, a halogenated C 1-6 alkoxy group, a C 1-6 alkoxy C 1-6 alkyl group, a mono-/di-C 2-7 alkanoyl amino group, a —C(═O)NH 2 group, or a C 1-6 alkoxy carbonyl group; and
R 2a and R 2b each independently represent a C 1-6 alkyl group.

6. The intermediate compound, the pharmaceutically acceptable salt thereof, or the solvate thereof according to claim 5 , wherein: R 1a and R 1b each independently represent a hydrogen atom.

7. The intermediate compound, the pharmaceutically acceptable salt thereof, or the solvate thereof according to claim 5 , wherein: R 2a and R 2b each independently represent methyl group.

8. The intermediate compound, the pharmaceutically acceptable salt thereof, or the solvate thereof according to claim 5 , wherein: R 1a and R 1b each independently represent a hydrogen atom, and R 2a and R 2b each independently represent methyl group.

9. A method of producing an intermediate compound represented by formula (AM-2-RR)⋅(D-TA):

in which
p represents an integer of 0 to 4;
R 1 each independently represent a halogen atom, a cyano group, a C 1-6 alkyl group, a halogenated C 1-6 alkyl group, a hydroxy C 1-6 alkyl group, a cyanated C 1-6 alkyl group, a halogenated C 1-6 alkoxy group, a C 1-6 alkoxy C 1-6 alkyl group, a mono-/di-C 2-7 alkanoyl amino group, a —C(═O)NH 2 group, or a C 1-6 alkoxy carbonyl group; and
R 2a and R 2b each independently represent a C 1-6 alkyl group,

the method comprising:
adding into a mixture solvent of water with a solvent selected from acetonitrile, acetone and 1,2-dimethoxyethane, D-tartaric acid and a racemic compound represented by formula (AM-2-Racemate):

where p, R 1 , R 2a , and R 2b are the same as the definitions of the formula (AM-2-RR)⋅(D-TA),
causing reaction by stirring the obtained mixture solution in a range of room temperature to a reflux temperature of the mixture solution, and
obtaining the intermediate compound represented by the formula (AM-2-RR)⋅(D-TA).

10. The method according to claim 9 , wherein the intermediate compound represented by the formula (AM-2-RR)⋅(D-TA) is obtained by allowing the reaction solution after the reaction to stand at room temperature or to cool to room temperature.

11. The method according to claim 9 , of producing a compound represented by the following formula (AM-2a-RR)⋅(D-TA):

in which
R 1a and R 1b each independently represent a hydrogen atom, a halogen atom, a cyano group, a C 1-6 alkyl group, a halogenated C 1-6 alkyl group, a hydroxy C 1-6 alkyl group, a cyanated C 1-6 alkyl group, a halogenated C 1-6 alkoxy group, a C 1-6 alkoxy C 1-6 alkyl group, a mono-/di-C 2-7 alkanoyl amino group, a —C(═O)NH 2 group, or a C 1-6 alkoxy carbonyl group; and
R 2a and R 2b each independently represent a C 1-6 alkyl group,

the method comprising:
adding into a mixture solvent of water with a solvent selected from acetonitrile, acetone and 1,2-dimethoxyethane, D-tartaric acid and a racemic compound represented by formula (AM-2a-Racemate):

where R 1a , R 1b , R 2a and R 2b are the same as the definitions of the formula (AM-2a-RR)⋅(D-TA),
causing reaction by stirring the obtained mixture solution in a range of room temperature to a reflux temperature of the mixture solution, and
obtaining the intermediate compound represented by the formula (AM-2a-RR)⋅(D-TA).

12. The method according to claim 11 , wherein the intermediate compound represented by the formula (AM-2a-RR)⋅(D-TA) is obtained by allowing the reaction solution after the reaction to stand at room temperature or to cool to room temperature.

Assignees

• Mochida Pharm Co Ltd

Inventors

• Kawada Yuji

Classifications

• C07D417/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D413/12

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

• C07D405/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D213/84

  Nitriles · CPC title

• C07D213/81

  Amides; Imides · CPC title