Optically active pyrrolidine compound and method for producing same

Patent metadata

Field	Value
Publication number	US-2021300902-A1
Application number	US-202117338138-A
Country	US
Kind code	A1
Filing date	Jun 3, 2021
Priority date	Sep 29, 2017
Publication date	Sep 30, 2021
Grant date	—

Abstract

The present invention provides: a methyl 1-{2-[(3S,4R)-1-[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidine-3-carbonyl]-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylate 1/2 ethane-1,2-disulfonic acid which is represented by formula (1) and is excellent in crystallinity; and a method for producing the same; and a production intermediate thereof; and a production method using this compound.

First claim

1 . A compound represented by formula (4):

or a pharmaceutically acceptable salt thereof,
wherein R 4 represents an alkyl having one to six carbon atoms which may be optionally substituted with aryl in which the aryl may be optionally substituted with alkoxy having one to six carbon atoms.

2 . A compound according to claim 1 , which is represented by formula (4-a):

or a pharmaceutically acceptable salt thereof,
wherein R 4 represents an alkyl having one to six carbon atoms which may be optionally substituted with aryl in which the aryl may be optionally substituted with alkoxy having one to six carbon atoms.

3 . A compound according to claim 2 , wherein R 4 represents a protecting group of amino group that is selected from the group consisting of methyl, ethyl, benzyl, p-methoxybenzyl 1-phenethyl, and benzyl.

4 . A method for making a compound according to claim 2 , by the following reaction scheme:

wherein
R 1 represents a protecting group for an amino group which is an alkyl having one to six carbon atoms which may be optionally substituted with aryl in which the aryl may be optionally substituted with alkoxy having one to six carbon atoms,
R 2 represents a silyl which is substituted with one to three alkyl having one to six carbon atoms or a cyano, and
R 3 represents an alkoxy having one to six carbon atoms, wherein the method comprises:

reacting a compound (2-a) with a compound (3) to obtain a compound (4-a) or a pharmaceutically acceptable salt thereof.

5 . The method according to claim 4 , wherein R 1 represents a benzyl, R 2 represents a trimethylsilyl, and R 3 represents a methoxy.

6 . A compound represented by formula (5):

or a pharmaceutically acceptable salt thereof,
wherein R 5 represents an alkyl having one to six carbon atoms which may be optionally substituted with aryl in which the aryl may be optionally substituted with alkoxy having one to six carbon atoms.

7 . The compound according to claim 6 , which is represented by formula (5-a):

or a pharmaceutically acceptable salt thereof,
wherein R 5 represents an alkyl having one to six carbon atoms which may be optionally substituted with aryl in which the aryl may be optionally substituted with alkoxy having one to six carbon atoms.

8 . A method for making a compound according to claim 7 , by the following reaction scheme:

wherein
R 1 represents a protecting group for an amino group which is an alkyl having one to six carbon atoms which may be optionally substituted with aryl in which the aryl may be optionally substituted with alkoxy having one to six carbon atoms,
R 2 represents a silyl which is substituted with one to three alkyl having one to six carbon atoms or a cyano, and
R 3 represents an alkoxy having one to six carbon atoms,
wherein the method comprises:

reacting a compound (2-a) or a pharmaceutically acceptable salt thereof, with a compound (3) to obtain a compound (4-a) or a pharmaceutically acceptable salt thereof; and
hydrolyzing the compound (4-a) or a pharmaceutically acceptable salt thereof to obtain a compound (5-a) or a pharmaceutically acceptable salt thereof.

9 . The method according to claim 8 , further comprising: removing a protecting group R 1 of an amino group in the compound (5-a) or a pharmaceutically acceptable salt thereof.

10 . A method for making a compound according to claim 7 , by the following reaction scheme:

wherein
R 1 represents a protecting group for an amino group which is an alkyl having one to six carbon atoms which may be optionally substituted with aryl in which the aryl may be optionally substituted with alkoxy having one to six carbon atoms,
wherein the method comprises:

hydrolyzing the compound (4-a) or a pharmaceutically acceptable salt thereof to obtain a compound (5-a) or a pharmaceutically acceptable salt thereof.

11 . A compound represented by formula (2):

or a pharmaceutically acceptable salt thereof.

12 . The compound according to claim 11 , represented by formula (2-a):

or a pharmaceutically acceptable salt thereof.

Assignees

• Mitsubishi Tanabe Pharma Corp

Inventors

• Tsurumoto Joji
• Morokuma Kenji

Classifications

• C07D263/26

  with hetero atoms or acyl radicals directly attached to the ring nitrogen atom · CPC title

• C07B61/00

  Other general methods · CPC title

• A61K31/454

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• C07D207/16

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07D413/06

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