FIELD OF THE INVENTION:
The present invention relates to a one pot synthesis of 6-fluoro-3-hydroxy-2-pyrazine carbonitrile and its pharmaceutically acceptable salts, which is an intermediate in the preparation of Favipiravir.
BACKGROUND OF THE INVENTION:
Favipiravir is chemically known as 6-fluoro-3-hydroxy-2-pyrazine carboxamide, and is structurally represented as
Favipiravir is being developed and manufactured by Toyama Chemical (Fujifilm Group) and was approved for medical use for influenza virus in Japan in 2014. Favipiravir was first used against SARS-CoV-2 in Wuhan at the very epicenter of the pandemic. And this drug received approval for emergency use in Italy, and currently has been in use in India, Russia, Ukraine, Bangladesh, UAE, Egypt, Uzbekistan, Moldova, and Kazakhstan.
There are several patents and publications which describes different methods for the preparation of Favipiravir. Few of the relevant methods pertaining to the present invention are given below:
Favipiravir was first disclosed in USRE43748E (US6787544), assigned to Toyama Chemical Co Ltd., which discloses a process for the preparation of Favipiravir, which is depicted in Scheme-1

US 8,168.789 B2, assigned to Toyama Chemical Co Ltd., discloses and claims organic amine salt of 6-Fluoro-3-Hydroxy-2-Pyrazine Carbonitrile, the process for the preparation of the same is depicted in Scheme -2
CN 102775358 B, assigned to Shandong Qidu Pharmaceutical Co., Ltd, discloses a process for preparing Favipiravir as shown in Scheme-3.

The present invention provides the preparation of 6-fluoro-3-hydroxy-2-pyrazine carbonitrile salts by one pot synthesis, without the complicated reaction steps of the prior art that requires strict conditions, thereby reducing the number of reaction steps for the preparation which needs a mild condition. Hence, the present invention provides an environment friendly, high-yield, commercially viable process for the preparation of 6-fluoro-3-hydroxy-2-pyrazine carbonitrile and its pharmaceutically acceptable salts.
OBJECTIVE OF THE INVENTION:
The main object of the present invention is to provide a one pot synthesis for the preparation of 6-fluoro-3-hydroxy-2-pyrazine carbonitrile and its pharmaceutically acceptable salts, which is an important intermediate in the preparation of Favipiravir.
SUMMARY OF THE INVENTION:
The main aspect of the present invention is to provide a one pot synthesis for the preparation of 6-fluoro-3-hydroxy-2-pyrazine carbonitrile and its pharmaceutically acceptable salts, which comprises the following steps:

DETAILED DESCRIPTION OF THE INVENTION:
The present invention relates to the preparation of one pot synthesis for the preparation of 6-fluoro-3-hydroxy-2-pyrazine carbonitrile and its ammonium salt, can be summarized as follows:
First, 6-Bromo-3-hydroxy-2-pyrazine carboxamide is treated with the chlorinating agent to obtain 3.6-Dichloro-2-pyrazine carboxamide, which is converted to 3,6-Difluro-2-pyrazine carbonitrile in-situ, which is in turn converted to 6-fluoro-3-hydroxy-2-pyrazine carbonitrile and its ammonium salt with high yield and purity.

According lo the first embodiment of the present invention, the Chlorination is carried out using the chlorinating agent and a base.
According to the second embodiment of the present invention, the fluorination is carried out using a Fluorinating agent, Phase transfer catalyst and a solvent.
According to other embodiment of the present invention the solvent used is selected from the group of water, DMSO, Toluene, DMF or a mixture thereof.
According to the third embodiment of the present invention the difluro compound is hydrolyzed using the base to obtain of 6-fluoro-3-hydroxy-2-pyrazine carbonitrile, which is further converted to its ammonium salt.