Chemical process for preparing spiroindolones and intermediates thereof

Patent metadata

Field	Value
Publication number	US-9598712-B2
Application number	US-201314384233-A
Country	US
Kind code	B2
Filing date	Mar 22, 2013
Priority date	Mar 23, 2012
Publication date	Mar 21, 2017
Grant date	Mar 21, 2017

Abstract

The present invention relates to processes and intermediates useful for the manufacture of spiroindolone compounds such as (1′R,3′S)-5,7′-dichloro-6′-fluoro-3′-methyl-2′,3′,4′,9′-tetrahydrospiro[indoline-3,1′-pyrido[3,4-b]indol]-2-one and salts and hydrates and solvates thereof.

First claim

The invention claimed is:

1. A process for preparing a compound of formula (II), or a salt, solvate, or hydrate thereof,

Comprising enzymatically converting a compound of formula (I) to compound of formula (II), or a salt, solvate or hydrate thereof,

wherein:
the enzyme is SEQ ID NO: 134
the dashed line is a bond or absent;
A is selected from C═O or C═NH; or when the dashed line is a double bond A-R 8 is:

R a is C 1-6 alkyl;
R 1 is H, —CH 3 ,

R 4 and R 7 are each, independently, H or —Cl;
R 5 is H, —OH, —CH 3 , —OCH 3 , —F, —Cl, —CF 3 or —CN;
R 6 is H, —OH, —OCH 3 , —F or —Cl;
R 8 is H, —CH 3 , —CH 2 CH 3 , —CH 2 OH, —CO 2 H, —CO 2 CH 2 CH 3 or —CF 3 ; and
n is 1 or 2.

2. The process of claim 1 , wherein R 5 and R 6 are fluoro when: R 8 is —CH 3 , and n is 1.

3. The process of claim 1 , wherein R 5 and R 6 are each, independently, fluoro or chloro, when: R 8 is —CH 3 , and n is 1.

4. The claim 1 , wherein R 5 and R 6 are hydrogen when: R 8 is —CH 3 and n is 1.

5. The process of claim 1 , wherein R 5 is fluoro when; n is 1, and R 6 is hydrogen.

6. The process of claim 1 , wherein the compound of formula (II) is of formula (IIA), or a salt or solvate or hydrate thereof,

7. The process according to claim 1 or 6 , wherein the compound of formula (I) is a compound of formula (IA) or a salt or hydrate, or solvate thereof,

Assignees

• Crowe Michael
• Foulkes Michael
• Francese Giancarlo
• Grimler Dominique
• Kuesters Ernst
• Laumen Kurt
• Li Yunzhong
• Lin Changxue
• Nazor Jovana
• Ruch Thomas
• Smith Derek
• Song Shiwei
• Teng Shangjun
• Novartis Ag

Inventors

• Crowe Michael
• Foulkes Michael
• Francese Giancarlo
• Grimler Dominique
• Kuesters Ernst
• Laumen Kurt
• Li Yunzhong
• Lin Changxue
• Nazor Jovana
• Ruch Thomas
• Smith Derek
• Song Shiwei
• Teng Shangjun

Classifications

• Y02P20/52

  using catalysts, e.g. selective catalysts · CPC title

• C12N9/1096

  transferring nitrogenous groups (2.6) · CPC title

• C07D209/12 Primary

  Radicals substituted by oxygen atoms · CPC title

• C07D209/34

  in position 2 · CPC title

• C07D405/06

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