The Synthetic Routes of [1-(6-Chloropyridazin-3-yl)piperidin-4-yl]methanol

The synthesis of [1-(6-chloropyridazin-3-yl)piperidin-4-yl]methanol, commonly referred to as CPMP, is an important step in the production of various pharmaceuticals and agrochemicals.
This compound has been shown to have a wide range of biological activities, including antimicrobial, anti-inflammatory, and antitumor effects, making it a valuable building block for the development of new drugs.

There are several different synthetic routes available for the preparation of CPMP, each with its own advantages and disadvantages.
In this article, we will explore some of the most commonly used synthetic routes and discuss their applications in the chemical industry.

1. Classical Synthesis Route
   The classical synthesis route for CPMP involves several steps, including the preparation of the starting materials, the reaction sequence, and the purification process.
   The overall process can be divided into the following steps:

a.
Preparation of 6-chloropyridazine-3-carboxylic acid
This step involves the chlorination of 6-aminopyridazine-3-carboxylic acid with chlorine gas or chloride salt, followed by acid hydrolysis to obtain the desired product.

b.
Preparation of 4-iodo-2,3,6-triiodopyridine
This step involves the iodination of 4-piperidone with iodine and sodium hydride, followed by thermal condensation to obtain the desired product.

c.
Preparation of N-[(1R)-1-(6-chloropyridazin-3-yl)-2,3-dihydro-1H-imidazo[4,5-f][1,4]benzoxazepin-9-yl]methanesulfonamide
This step involves the reaction of 9-substituted fluorene-1,4-dihydroxylamines with N-[(2S)-2-[[5-(difluoromethyl)-2-oxo-1,3-oxazolidin-3-yl]amino]-5-(4,4,5,5-tetrafluoro-1-oxonaphthalen-2-ylmethoxy]acetamide, followed by hydrolysis and coupling with N-[(1R)-1-(6-chloropyridazin-3-yl)-2,3-dihydro-1H-imidazo[4,5-f][1,4]benzoxazepin-9-yl]methanesulfonamide, which is then reduced to obtain the desired product.

d.
Purification of CPMP
The final product is purified using various techniques, such as column chromatography, recrystallization, and high-performance liquid chromatography (HPLC).

1. Hydrogenation Route
   The hydrogenation route involves the reduction of the nitrile group in CPMP to an alcohol group using hydrogen gas in the presence of a catalyst.
   The overall process can be divided into the following steps:

a.
Preparation of CPMP
This step involves the synthesis of CPMP by the classical synthesis route, followed by hydrogenation of the nitrile group to an alcohol group using palladium on barium sulfate as the hydrogenation catalyst.

b.
Purification of CPMP
The final product is purified using HPLC or a combination of HPLC and mass spectrometry (MS) to ensure purity and identity.

1. Microwave-Assisted Route
   The microwave-assisted route involves the use of microwave irradiation to accelerate the synthesis of CPMP.
   This route has the advantage of reducing the reaction time and the need for toxic reagents and solvents.
   The overall process can be divided into the following steps: