Chemical process for preparing spiroindolones and intermediates thereof
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.
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,