Processes for producing diazabicyclooctane compounds

Patent metadata

Field	Value
Publication number	US-10604522-B2
Application number	US-201816148774-A
Country	US
Kind code	B2
Filing date	Oct 1, 2018
Priority date	Oct 8, 2013
Publication date	Mar 31, 2020
Grant date	Mar 31, 2020

Abstract

A process for producing a compound of the following Formula (VII-CR):

The process involving providing a compound represented by the following Formula (VI):

in a case where the R 3 ONHC(═O) side chain in the compound of the Formula (VI) has a protecting group, removing the protecting group from the compound of the Formula (VI) with an acid, and adding an ester-based poor solvent to the resultant reaction solution to precipitate the compound of Formula (VII-CR), wherein in the compounds of the Formulas (VII-CR) and (VI), R 3 is a C 1-6 alkyl or a heterocycle.

First claim

The invention claimed is:

1. A process for producing a compound represented by the following Formula (VII-CR):

the process comprising:
(a) providing a compound represented by following Formula (VI):

wherein the R 3 ONHC(═O) side chain in the compound of the Formula (VI) has a protecting group,
(b) removing the protecting group from the compound of the Formula (VI) with an acid, and
(c) cooling the resultant reaction solution and adding an ester-based poor solvent to the resultant reaction solution to precipitate the compound represented by the Formula (VII-CR),
wherein in each of the Formulas VI and VII-CR, R 3 is a C 1-6 alkyl or a heterocyclyl, wherein R 3 is optionally substituted with 1 to 5 R 4 groups, wherein R 4 is selected from the group consisting of a C 1-6 alkyl, a heterocyclyl, R 5 (R 6 )N- and a protecting group, wherein R 4 is optionally substituted with one or more groups selected from the group consisting of a C 1-6 alkyl, a heterocyclyl, R 5 (R 6 )N- and a protecting group, wherein R 5 and R 6 each independently is hydrogen or a C 1-6 alkyl or together form a heterocyclyl, wherein R 3 , R 5 and R 6 can together undergo ring closure.

2. The process according to claim 1 , wherein in step (c), an amount added of the ester-based poor solvent is 1 to 3 times a volume of the reaction solution.

3. The process according to claim 1 , wherein in step (c), an amount added of the ester-based poor solvent is 1.5 to 2 times a volume of the reaction solution.

4. The process according to claim 1 , wherein R 3 in the Formulas (VI) and (VII-CR) is each independently selected from the group consisting of:
2-(tert-butoxycarbonylamino)ethyl,
2-aminoethyl,
2-((tert-butoxycarbonyl)(methyl)amino)ethyl,
2-(methylamino)ethyl,
2-((tert-butoxycarbonyl)(isopropyl)amino)ethyl,
2-(isopropylamino)ethyl,
2-(dimethylamino)ethyl,
(2S)-2-((tert-butoxycarbonyl)amino)propyl,
(2S)-2-(amino)propyl,
(2R)-2-((tert-butoxycarbonyl)amino)propyl,
(2R)-2-(amino)propyl,
3-((tert-butoxycarbonyl)amino)propyl,
3-(amino)propyl,
(2S)-tert-butoxycarbonylazetidin-2-ylmethyl,
(2S)-azetidin-2-ylmethyl,
(2R)-tert-butoxycarbonylpyrrolidin-2-ylmethyl,
(2R)-pyrrolidin-2-ylmethyl,
(3R)-tert-butoxycarbonylpiperidin-3-ylmethyl,
(3R)-piperidin-3-ylmethyl,
(3S)-tert-butoxycarbonylpyrrolidin-3-yl,
(3S)-pyrrolidin-3-yl,
1-(tert-butoxycarbonyl)azetidin-3-yl and azetidin-3-yl.

5. A process for producing a compound represented by the following Formula (VII-1-CR):

the process comprising: (a) providing a compound represented by the following Formula (VI-1):

(b) removing the tert-butoxycarbonyl (Boc) group from the compound of the Formula (VI-1) with trifluoroacetic acid, and (c) cooling the resultant reaction solution and adding ethyl acetate into the resultant reaction solution to precipitate the compound represented by the Formula (VII-1-CR).

6. The process according to claim 5 , wherein in step (c), an amount added of the ethyl acetate is 1 to 3 times a volume of the reaction solution.

7. The process according to claim 5 , wherein in step (c), an amount added of the ethyl acetate is 1.5 to 2 times a volume of the reaction solution.

Assignees

• Meiji Seika Pharma Co Ltd

Inventors

• Abe Takao
• Furuuchi Takeshi
• Sakamaki Yoshiaki
• Mitsuhashi Nakako
• Saito Yumiko

Classifications

• C07D471/08 Primary

  Bridged systems · CPC title

• A61K31/439

  the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46) · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title