Optically active pyrrolidine compound and method for producing same

Patent metadata

Field	Value
Publication number	US-11053217-B2
Application number	US-201816651049-A
Country	US
Kind code	B2
Filing date	Sep 28, 2018
Priority date	Sep 29, 2017
Publication date	Jul 6, 2021
Grant date	Jul 6, 2021

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

The invention claimed is:

1. 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):

2. A 1/2 ethane-1,2-disulfonic acid salt of a compound (1′):

wherein the compound is in crystalline form.

3. A method for preparing a compound represented by formula (11):

or a pharmaceutically acceptable salt thereof, which comprises a step of hydrolyzing 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 to provide a compound of formula (11), and
optionally, further converting the compound of formula (11) to a salt thereof.

4. A method for making 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 shown 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 the following steps:

(a) a step of reacting a compound (2-a) with a compound (3) to obtain a compound (4-a) or a salt thereof,
(b) a step of hydrolyzing the compound (4-a) or a salt thereof to obtain a compound (5-a) or a salt thereof,
(c) a step of removing a protecting group R 1 of an amino group in the compound (5-a) or a salt thereof, followed by reacting with a compound (6) to obtain a compound (7-a) or a salt thereof,
(d) a step of condensing the compound (7-a) or a salt thereof with a compound (8) or a salt thereof to obtain a compound (1′) or a salt thereof, and
(e) a step of reacting the compound (1′), or the compound (1′) which is obtained by desalting of a salt of the compound (1′), with a compound (9) to obtain a compound (1).

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

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

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• C07D401/10 Primary

  linked by a carbon chain containing aromatic rings · CPC title

• A61K31/454

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

• C07B61/00

  Other general methods · CPC title