The Synthetic Routes of 1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylicacid

The Synthetic Routes of 1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylicacid

1. Introduction

1.
1 Background

In the field of organic synthesis, the discovery of new methods for the synthesis of complex natural products and pharmaceuticals is an ongoing process.
One such compound is 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid (compound X).
Compound X is a potent and specific inhibitor of the Wnt signaling pathway and was identified as a potential drug candidate for the treatment of various cancers.
The total synthesis of compound X was reported by Li et al.
in 2014, and it involves a complex sequence of seven synthetic steps, which can be challenging to execute in the industrial setting.
The aim of this article is to discuss alternative synthetic routes for compound X and their potential industrial application.

1.
2 Synthetic Routes of Compound X

The total synthesis of compound X as reported by Li et al.
involved seven steps, which are outlined below:

Step 1: Synthesis of 2,6-dimethyl-5-fluoro-1,4-benzenedicarboxylic acid

This step involved the condensation of 2,6-dimethylphenol with 4-fluorobenzoic acid.

Step 2: Synthesis of 2-(2,6-dimethyl-5-fluorobenzoyl)-6-fluorabenzoic acid

This step involved the condensation of 2,6-dimethyl-5-fluoro-1,4-benzenedicarboxylic acid with 6-fluorobenzoic acid.

Step 3: Synthesis of 1,4-dihydro-8-(2-(2,6-dimethyl-5-fluorobenzoyl)-6-fluorobenzooxy)-7-methoxy-2H-pyrrolo[3,4-b]pyridine-2-carboxylic acid

This step involved the condensation of 1,4-dihydro-8-aminomethyl-2H-pyrrolo[3,4-b]pyridine-2-carboxylic acid with 2-(2,6-dimethyl-5-fluorobenzoyl)-6-fluorobenzoic acid.

Step 4: Synthesis of 1,4-dihydro-8-((4S)-4-((2-(7-methoxy-2H-pyrrolo[3,4-b]pyridin-3-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxepin-3-yl)-2-(2,6-dimethyl-5-fluorobenzoyl)-6-fluor-4-oxo-3-quinolinecarboxyl)amino)-3-oxo-2,6-dimethyl-5-fluorophtalimido)propanamide

This step involved the condensation of 1,4-dihydro-8-((4S)-4-((2-(7-methoxy-2H-pyrrolo[3,4-b]pyridin-3-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxepin-3-yl)-2-(2,6-dimethyl-5-fluorobenzoyl)-6-fluor-4-oxo-3-quinolinecarboxyl)amino)-3-oxo-2,6-dimethyl-5-fluorophtalimido)propanamide with N-prop