The Production Process of N-[4-(1-Cyanocyclopentyl)phenyl]-2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide methanesulfonate

The Production Process of N-[4-(1-Cyanocyclopentyl)phenyl]-2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide Methanesulfonate in the Chemical Industry: An Overview

N-[4-(1-Cyanocyclopentyl)phenyl]-2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide methanesulfonate, commonly known as MK-8628, is a synthetic compound that is used in the treatment of glaucoma, a condition that results in increased pressure within the eye, leading to damage to the optic nerve and loss of vision.
The production process of MK-8628 involves several stages, each of which requires careful monitoring and control to ensure the quality and purity of the final product.
This article provides an overview of the production process of MK-8628 in the chemical industry, highlighting the key steps involved in the manufacturing of this vital pharmaceutical compound.

Stage 1: Synthesis of 4-(1-cyanocyclopentyl)phenylamine
The synthesis of 4-(1-cyanocyclopentyl)phenylamine, also known as N-[4-(1-cyanocyclopentyl)phenyl]-2-pyridinecarboxamide, is the first step in the production of MK-8628.
This compound is synthesized by reacting cyanocyclopentene with benzaldehyde in the presence of a base, such as sodium hydroxide, followed by nitration with nitric acid to form 4-(1-cyanocyclopentyl)phenylnitrene.
This compound is then reduced to form N-[4-(1-cyanocyclopentyl)phenyl]-2-pyridinecarboxamide using hydrogen in the presence of a reducing agent, such as iron powder or sodium borohydride.

Stage 2: Synthesis of 2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide
In this stage, the synthesis of 2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide, also known as N-[4-(1-cyanocyclopentyl)phenyl]-2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide, is carried out.
This compound is synthesized by reacting N-[4-(1-cyanocyclopentyl)phenyl]-2-pyridinecarboxamide with (4-pyridinylmethyl)amine in the presence of a condensing agent, such as dicyclohexylcarbodiimide (DCC), and a catalyst, such as hydrochloric acid.

Stage 3: Synthesis of N-[4-(1-Cyanocyclopentyl)phenyl]-2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide Methanesulfonate
The final step in the production of MK-8628 is the synthesis of N-[4-(1-cyanocyclopentyl)phenyl]-2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide methanesulfonate.
This compound is synthesized by reacting N-[4-(1-cyanocyclopentyl)phenyl]-2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide with methanesulfonic acid in the presence of a catalyst, such as pyridine.

Quality Control and Purification
After the synthesis of N-[4-(1-cyanocyclopentyl)phenyl]-2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide methanesulfonate, the compound is subjected to rigorous quality control tests to ensure that it meets the required standards for purity and efficacy.
This involves the use of various analytical techniques, such as high-performance liquid chromatography (HPLC) and mass spectrometry