DESC: “PROCESS OF MOLNUPIRAVIR”

FIELD OF THE INVENTION

The present invention relates to a process for preparation of Molnupiravir (1) by employing novel compound of formula (2), (3) and (4). The present invention is also relates to an improved and commercially viable process of Molnupiravir with high yield and purity.

BACKGROUND OF THE INVENTION

Molnupiravir (development codes MK-4482 and EIDD-2801) is an experimental antiviral drug which is orally active and was developed for the treatment of influenza. It is a prodrug of the synthetic nucleoside derivative N4-hydroxycytidine, and exerts its antiviral action through introduction of copying errors during viral RNA replication. Activity has also been demonstrated against coronaviruses including SARS, MERS and SARS-CoV-2.

In April 2020, a whistleblower complaint by former Head of US Biomedical Advanced Research and Development Authority (BARDA) Rick Bright revealed concerns over providing funding for the further development of Molnupiravir due to similar drugs having mutagenic properties (producing birth defects). A previous company, Pharmasset, that had investigated the drug's active ingredient had abandoned it. These claims were denied by George Painter, CEO of DRIVE, noting that toxicity studies on Molnupiravir had been carried out and data provided to regulators in the US and UK, who permitted safety studies in humans to move forward in the spring of 2020. Also at this time, DRIVE and Ridgeback Biotherapeutics stated they planned future safety studies in animals.

After being found to be active against SARS-CoV-2 in March 2020, Molnupiravir was tested in a preliminary human study for "Safety, Tolerability, and Pharmacokinetics" in healthy volunteers in the UK and US. In June 2020, Ridgeback Bio therapeutics announced it was moving to Phase II trials to test the efficacy of the drug as a treatment for COVID-19. Two trials of small numbers of hospitalized and non-hospitalized patients in the US and the UK were underway in July. In late July 2020, and without yet releasing any medical data, Merck, which had been partnering with Ridgeback Biotherapeutics on developing the drug, announced its intention to move Molnupiravir to late stage trials beginning in September 2020. On October 19 2020, Merck began a one-year Stage 2/3 trial focused on hospitalized patients.

On December 3rd, 2020, an article was published in the journal Nature on the results of a study on the treatment with Molnupiravir of ferrets infected with Covid-19. The study found that the drug was "efficacious" when administered orally to infected ferrets, and that it blocked the transmission of the virus between ferrets after 24 hours following administration of the drug. Molnupiravir structural formula is as follows:

Molnupiravir is reported in US 20200276219by Emory University. The synthetic process for Molnupiravir is reported in US ‘219, which comprises Uridine (VI) is reacted with acetone in presence of H2SO4 /TEA to obtain the compound of formula (VII). The compound of formula (VII) is reacted with 2-methylpropanoyl 2-methyl propanoate in presence of TEA/4-DMAP and EtOAc to obtain the compound of formula (VIII). The compound of formula (VIII) is reacted with 1,2,4-triazole in presence of MeCN/N,N-diethylethanamine/POCl3/H2O and MDC to obtain the compound of formula (IX). The compound of formula (IX) is reacted with NH2OH in presence of IPA / EtOAc and H2O to obtain the compound of formula (V). The compound of formula (V) deprotected with HCOOH in presence of MTBE/IPA to obtain Molnupiravir (I).

The above process is schematically shown as below:

Synlett (2021), 32(3), 326-328discloses a process for the preparation of Molnupiravir (1), which comprisesCytidine (II) is reacted with 2,2-dimethoxypropane in presence of acetone and H2SO4 to obtain 2',3'-O-(1-methylethylidene)- sulfate Cytidine (III). The compound of formula (III) is reacted with isobutyric anhydride in presence of DBU / DMAP / MeCN / EtOAc / H2O and sodium bicarbonate to obtain 2',3'-O-(1-methylethylidene)-5'-(2- methyl propanoate) Cytidine (IV). The compound of formula (IV) is reacted with NH2OH.H2SO4 in presence of IPA / H2O / EtOAc / NaHCO3 and toluene to obtain 2',3'-O-(1-methylethylidene)-4-oxime-5'- (2-methyl propanoate) Uridine (V). The compound of formula (V) deprotected with HCO2H to obtain Molnupiravir (I).

The above process is schematically shown as below:

Above the approaches make use of very high risk and difficult. Further, the process obtain very low yield and unfavorable for scale up.
The processes taught by prior art have several drawbacks namely not suitable for scale up at plant level, difficult, giving lower yields and less user friendly. Considering the drawbacks of prior art for the preparation of the Molnupiravir, there is a urgent and pressing need for simple, energy economical, financially cheaper plant friendly process, environment friendly process for the preparation of Molnupiravir with better yields and purity.
Hence, there is consequently a need development for new methods to sort out prior art existing methods. So, our inventors have developed a novel method for the preparation of Molnupiravir. The present invention is providing a simple, cost effective with high purity and good yield on industrial applicable process.
SUMMARY OF THE INVENTION

The present invention relates to a process for preparation of Molnupiravir (1) by employing novel compound of formula (2), (3) and (4). The present invention is also relates to an improved and commercially viable process of Molnupiravir with high yield and purity.

The one embodiment of the present invention provides a process for the preparation of Molnupiravir (I), comprising the steps of;

a) Cytidine (5) is reacted with Aldehyde or Acetal and sulfuric acid (H2SO4) in presence of organic solvent to obtain the compound of formula (4),

Wherein Aldehyde is Formaldehyde, Benzaldehyde and 4-Anisaldehyde; Acetal is Formaldehyde dimethyl acetal, Benzaldehyde dimethyl acetal, Anisaldehyde dimethyl acetal, (1,1-Dimethoxyethyl)benzene;
wherein R is hydrogen, phenyl or substituted phenyl group;

b) The compound of formula (4) is reacted with isobutyric anhydride in presence of organic base and organic solvent to obtain the compound of formula (3),

c) The compound of formula (3) is reacted with hydroxylamine sulphate in presence of organic solvent to obtain the compound of formula (2),

d) The compound of formula (2) is deprotected with acid in presence of organic solvent to obtain Molnupiravir (I), and

e) Isolated the Molnupiravir (I).
In yet another embodiment of the present invention provides a novel compound of formula (2), (3) and (4).

wherein R is hydrogen, phenyl or substituted phenyl group;

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a process for preparation of Molnupiravir (1) by employing novel compound of formula (2), (3) and (4). The present invention is also relates to an improved and commercially viable process of Molnupiravir with high yield and purity.

The one embodiment of the present invention provides a process for the preparation of Molnupiravir (I), comprising the steps of;

a) Cytidine (5) is reacted with Aldehyde or Acetal and sulfuric acid (H2SO4) in presence of organic solvent to obtain the compound of formula (4),

Wherein Aldehyde is Formaldehyde, Benzaldehyde and 4-Anisaldehyde; Acetal is Benzaldehyde dimethyl acetal, Anisaldehyde dimethyl acetal, (1,1-Dimethoxyethyl)benzene;
wherein R is hydrogen, phenyl or substituted phenyl group;

b) The compound of formula (4) is reacted with isobutyric anhydride in presence of organic base and organic solvent to obtain the compound of formula (3),

c) The compound of formula (3) is reacted with hydroxylamine sulphate in presence of organic solvent to obtain the compound of formula (2),

d) The compound of formula (2) is deprotected with acid in presence of organic solvent to obtain Molnupiravir (I), and

e) Isolated the Molnupiravir (I).

In an embodiment of the present invention, Cytidine (5) is reacted with Aldehyde or Acetal and sulfuric acid (H2SO4) in presence of organic solvent and the reaction is carried out at 20-35ºC for 3-6 hours to obtain the compound the compound of formula (4). The compound of formula (4) is reacted with isobutyric anhydride in presence of organic base and organic solvent and the reaction is carried out at 0-30ºC for 1-2 hours to obtain the compound of formula (3). The compound of formula (3) is reacted with hydroxylamine sulfatein presence of organic solvent and purified water by Karl Fisher titration and the reaction is carried out at 60–90°C for 20-25 hours to obtain the compound of formula (2). The compound of formula (2) is deprotected with acid in presence of organic solvent and the reaction is carried out at 15-45°C for 1-2 hours, the reaction mass pH should between7.0-9.0 by using sodium carbonate solution to obtain Molnupiravir (I) and further provides purification process for the preparation of Molnupiravir (I), comprising the Molnupiravir purified with organic solvent and the reaction is carried out at 60-90°C for 05-15 min to obtain pure Molnupiravir (I).

According to an embodiment of the present invention provides pure Molnupiravir (I) having 99.9% having HPLC purity.

According to an embodiment of the present invention, wherein the organic solvent is selected from acetone, acetonitrile, ethyl acetate, water, isopropyl alcohol, methanol, ethanol, toluene, dimethyl sulfoxide (DMSO), dimethylformamide (DMF),isopropyl acetate and n-butyl acetate, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, dichloromethane (MDC), dichloroethane, carbon tetrachloride and chloroform and/or mixtures thereof.

According to an embodiment of the present invention, wherein the organic base is selected from 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), Dimethylaminopyridine (DMAP), 5-diazabicyclo[4.3.0]non-5-ene (DBN), pyridine, triethylamine (TEA), Diisopropylethylamine (DIPEA), trimethylamine, diethylamine and N,N-dimethylaniline.

According to an embodiment of the present invention, wherein the acid is selected from trifluoroacetic acid, formic acid, acetic acid and hydrochloric acid.
In yet another embodiment of the present invention provides a novel compound of formula (2), (3) and (4).

wherein R is hydrogen, phenyl or substituted phenyl group;

The following examples illustrate the present invention, but should not be construed as limiting the scope of the invention.

EXAMPLES

Example-1:

Preparation of4-amino-1-((3aR,4R,6R,6aR)-6-(hydroxymethyl)-2-phenyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)pyrimidin-2(1H)-one sulfate:
Charge Acetone (100ml), Cytidine (10 gm) and benzaldehyde dimethyl acetal (36.9gm) into RB Flask and add sulphuric acid (7.3gm) into flask at below 30°C. Stir the mass at 25-30°C for 4-5 hours. After completion of the reaction, Filter the material and wash the material with acetone (30 ml). Suck dry the material for 20 min. Charge Ethyl acetate (70 ml) and crude wet material into RB Flask. Stir the mass for 60 min at 25-30°C. Filter the material and wash the material with Ethyl acetate (30 ml) and Suck dry the material for 20 min. Unload the material. obtain the 35.0gm of wet off white colour.
Example-2:

Preparation of((3aR,4R,6R,6aR)-6-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-phenyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl isobutyrate.
Charge Acetonitrile (75.0 ml) and above Example 1 (35.0gm) wet material into 4NRB Flask at 25-30°C. Charge 1, 8-Diazabicyclo[5.4.0]undec-7-ene (DBU) (12.75 ml into flask at 25-30°C. Stir the mass for 10 min to clear solution. Charge 4-Dimethylamino pyridine (DMAP) (0.75 gm) into flask. Cool the mass to 0-5°C. Slowly add isobutyric anhydride (6.9 ml) into mass at 0-5°C. Stir the mass for 60 min. After completion of the reaction, Charge purified water (150 ml) and Dichloromethane (105 ml) into flask, Stir the mass for 10 min and separate the two layers. Extract the product from aqueous layer with Dichloromethane (45 ml). wash the total the organic layer with 10% Sodium bicarbonate solution (30 ml). Separate the two layers. Take the organic layer (MDC Layer) and concentrate the mass under reduced pressure at below 50°C. Obtain the 15.6 gm (94.5% of yield from Cytidine) of thick residue with 92.13% purity.
Example-3:

Preparation of ((3aR,4R,6R,6aR)-6-(4-(hydroxyamino)-2-oxopyrimidin-1(2H)-yl)-2-phenyltetra
hydrofuro[3,4-d][1,3]dioxol-4-yl)methyl isobutyrate.
Charge Isopropyl alcohol (145 ml), purified water (41.4 ml((3aR,4R,6R,6aR)-6-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-phenyltetrahydrofuro[3,4-d] [1,3]dioxol-4-yl)methyl isobutyrate (example 2) (15.6 gm) and Hydroxylamine sulphate (17.25 gm) into 4NRB Flask at 25-30°C. Raise the mass temperature to 70-80°C. Maintain the mass for 24 hours at 70-80°C. After completion of the reaction concentrate the mass under reduced pressure at below 70°C. Cool the mass to below 30°C. Charge purified water (138 ml) into flask. Charge 10% sodium carbonate solution into flask. Stir the mass for 60 min. Filter the material at 25-30°C. Wash the material with purified water (27.6 ml) and suck dry the material for 10 min. Obtain the crude material with 95.37% of purity Charge Toluene (13.8 ml) and charge crude wet material (~17.0 gm). Stir the mass for 30 min at 25-30°C and cool the mass to 0-5°C. Stir the mass for 20 min. Filter the material and wash the material with toluene (2.76 ml). Suck dry the material for 10 min. Dry the material for 8 hours at 55-60°C. Obtain the 13.3gm (85.2% of yield) of off white colour solid with 96.2% purity.
Example-4:

Preparation of ((2R,3S,4R,5R)-3,4-dihydroxy-5-(4-(hydroxyamino)-2-oxopyrimidin-1(2H)-yl) tetrahydrofuran-2-yl)methyl isobutyrate or Molnupiravir.
Charge dichloromethane (40.0ml) and ((3aR,4R,6R,6aR)-6-(4-(hydroxyamino)-2-oxopyrimidin-1(2H)-yl)-2-phenyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl isobutyrate (example 3) (10.0gm) into RB Flask. Add the Trifluoro acetic acid (30.0 ml) into flask at below 35°C. Stir the mass at 30-35°C for 70-80 hours. Monitor the reaction mass by HPLC (Unreacted upto ~8-10%). After completion of the reaction, Concentrate the reaction mass at below 40°C under reduced pressure. Cool the reaction mass to 25-30°C. Charge Ethyl acetate (10.0ml) into flask. Adjust the mass pH to 7.0-8.5 with 10% Sodium carbonate solution (~70 ml) and charge purified water(100of white color material with 99.81% of Purity. ml) into flask. Charge dichloromethane (20 ml) into flask. Stir and settle the mass for 15 min. Separate the two layers. Take aqueous layer (organic layer) into flask and charge dichloromethane (20 ml) into flask. Stir and settle the mass for 15 min. Separate the two layers. Take the aqueous layer (organic layer) into flask. Charge Ethyl acetate (100 ml) into flask. Stir and separate the two layers. Take the aqueous layer and charge sodium chloride (10.0gm) into flask. Stir for 5 min and charge Ethyl acetate (100 ml) into flask. Stir and separate the two layers. Take the aqueous layer into flask and repeat the extraction of product into ethyl acetate (3×100 ml) by adding sodium chloride (3×10 gm) for three times and separate the layers. Take the aqueous layer and extract the product with ethyl acetate (2×100 ml) for two times. Separate the two layers. Take the total ethyl acetate layer into flask. Charge 30% sodium chloride solution (10 ml) into flask. Stir for 15 min and separate the two layers. Wash the ethyl acetate layer with 30% sodium chloride solution for 4 times (4×10 ml) and separate the two layers. Take the Ethyl acetate layer into flask. Filter the mass through hyflow bed and wash the hyflow bed with ethyl acetate (10.0 ml) in to another 4NRB Flask. Distil out the Ethyl acetate under reduced pressure at below 60°C. Degas the mass for 2 hours under reduced pressure at below 60°C. Charge Ethyl acetate (40 ml) into flask and stir the mass for 15 min at 60-65°C. Cool the mass to 25-30°C. Stir the mass for 60 min and filter the material at 25-30°C. Wash the material with Ethyl acetate (25 ml). Suck dry and obtain 11 gm of wet material with 95.2% of purity.
Example-5:

Preparation of 4-amino-1-((3aR,4R,6R,6aR)-6-(hydroxymethyl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)pyrimidin-2(1H)-one sulfate.
Charge Acetone (100ml), Cytidine (10 gm) and Formaldehyde dimethyl acetal (18.6gm) into RB Flask. Add sulphuric acid (7.3gm) into flask at below 30°C. Stir the mass at 25-30°C for 4-5 hours. After completion of the reaction, Filter the material and wash the material with acetone (30 ml). Suck dry the material for 20 min. Charge Ethyl acetate (70 ml) and crude wet material into RB Flask. Stir the mass for 60 min at 25-30°C. Filter the material and wash the material with Ethyl acetate (30 ml). Suck dry the material for 20 min. Unload the material. obtain the 30.0 gm of wet off white colour material.
Example-6:

Preparation of ((3aR,4R,6R,6aR)-6-(4-amino-2-oxopyrimidin-1(2H)-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl isobutyrate.
Charge Acetonitrile (75.0 ml) and above example 05 (30.0gm) wet material into 4NRB Flask at 25-30°C. Charge 1,8- Diazabicyclo[5.4.0]undec-7-ene (DBU) (13.75 ml into flask at 25-30°C. Stir the mass for 10 min to clear solution. Charge 4-Dimethylamino pyridine (DMAP) (0.75 gm) into flask. Cool the mass to 0-5°C. Slowly add isobutyric anhydride (7.14 gm) into mass at 0-5°C. Stir the mass for 60 min. After completion of the reaction, Charge purified water (150 ml) and Dichloromethane (105 ml) into flask, Stir the mass for 10 min and separate the two layers. Extract the product from aqueous layer with Dichloromethane (45 ml). wash the total the organic layer with 10% Sodium bicarbonate solution (30 ml). Separate the two layers. Take the organic layer (MDC Layer) and concentrate the mass under reduced pressure at below 50°C. Obtain the 12.7 gm (95.0% of yield from Cytidine) of thick residue with 93.1% purity.
Example-7:

Preparation of ((3aR,4R,6R,6aR)-6-(4-(hydroxyamino)-2-oxopyrimidin-1(2H)-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl isobutyrate.
Charge Isopropyl alcohol (145 ml), purified water (41.4 ml((3aR,4R,6R,6aR)-6-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-phenyltetrahydrofuro[3,4-d] [1,3]dioxol-4-yl) methyl isobutyrate (example 06) (12.7gm) and Hydroxylamine sulphate (18.5 gm) into 4NRB Flask at 25-30°C. Raise the mass temperature to 70-80°C. Maintain the mass for 24 hours at 70-80°C. After completion of the reaction concentrate the mass under reduced pressure at below 70°C. Cool the mass to below 30°C. Charge purified water (138 ml) into flask. Charge 10% sodium carbonate solution into flask. Stir the mass for 60 min. Filter the material at 25-30°C. Wash the material with purified water (27.6 ml) and suck dry the material for 10 min. Obtain the crude material with 95.37% of purity Charge Toluene (13.8 ml) and charge crude wet material (~17.0 gm). Stir the mass for 30 min at 25-30°C and cool the mass to 0-5°C. Stir the mass for 20 min. Filter the material and wash the material with toluene (2.76 ml). Suck dry the material for 10 min. Dry the material for 8 hours at 55-60°C. Obtain the 11.5gm (87.0%) of off white colour solid with 97.2% purity.
Example-8:

Preparation of ((2R,3S,4R,5R)-3,4-dihydroxy-5-(4-(hydroxyamino)-2-oxopyrimidin-1(2H)-yl) tetrahydrofuran-2-yl) methyl isobutyrate or Molnupiravir.
Charge dichloromethane (40.0ml) and ((3aR,4R,6R,6aR)-6-(4-(hydroxyamino)-2-oxopyrimidin-1(2H)-yl)-2-phenyltetrahydrofuro[3,4-d] [1,3] dioxol-4-yl) methyl isobutyrate (example 07) (10.0gm) into RB Flask. Add the Trifluoro acetic acid (30.0 ml) into flask at below 35°C. Stir the mass at 30-35°C for 70-80 hours. Monitor the reaction mass by HPLC (Unreacted upto ~8-10%). After completion of the reaction, Concentrate the reaction mass at below 40°C under reduced pressure. Cool the reaction mass to 25-30°C. Charge Ethyl acetate (10.0ml) into flask. Adjust the mass pH to 7.0-8.5 with 10% Sodium carbonate solution (~70 ml) and charge purified water (100 of white colour material with 99.81% of Purity. ml) into flask. Charge dichloromethane (20 ml) into flask. Stir and settle the mass for 15 min. Separate the two layers. Take aqueous layer (organic layer) into flask and charge dichloromethane (20 ml) into flask. Stir and settle the mass for 15 min. Separate the two layers. Take the aqueous layer (organic layer) into flask. Charge Ethyl acetate (100 ml) into flask. Stir and separate the two layers. Take the aqueous layer and charge sodium chloride (10.0gm) into flask. Stir for 5 min and charge Ethyl acetate (100 ml) into flask. Stir and separate the two layers. Take the aqueous layer into flask and repeat the extraction of product into ethyl acetate (3×100 ml) by adding sodium chloride (3×10 gm) for three times and separate the layers. Take the aqueous layer and extract the product with ethyl acetate (2×100 ml) for two times. Separate the two layers. Take the total ethyl acetate layer into flask. Charge 30% sodium chloride solution (10 ml) into flask. Stir for 15 min and separate the two layers. Wash the ethyl acetate layer with 30% sodium chloride solution for 4 times (4×10 ml) and separate the two layers. Take the Ethyl acetate layer into flask. Filter the mass through hyflow bed and wash the hyflow bed with ethyl acetate (10.0 ml) in to another 4NRB Flask. Distil out the Ethyl acetate under reduced pressure at below 60°C. Degas the mass for 2 hours under reduced pressure at below 60°C. Charge Ethyl acetate (40 ml) into flask and stir the mass for 15 min at 60-65°C. Cool the mass to 25-30°C. Stir the mass for 60 min and filter the material at 25-30°C. Wash the material with Ethyl acetate (25 ml). Suck dry and obtain 11.8gm of wet material with 96.3% of purity.
Example-9:

Purification of Molnupiravir
Charge isopropyl alcohol (60 ml) and crude wet material of Molnupiravir (11.0 gm) into flask. Stir the mass at 70-80°C for 10-15 min to dissolve the material. Charge activated carbon (0.5 gm) and stir for 10 min at the same temperature. Filter the mass through hyflow bed into another RB Flask and wash the hyflow bed with isopropyl alcohol (10ml) and charge purified water (14 ml) into flask. Stir the mass for 70-80°C for 10 min to dissolve the material. Cool the mass to 25-30°C. Stir the mass for 45-60 min. Filter the material at 25-30°C and wash the material with isopropyl alcohol (3.0 ml). Dry the material at 60-65°C for 8 hours, obtain the 7.0gm (85.5% of yield) of white colour material off white colour material with 99.85% of Purity.

Example-10:

Purification of Molnupiravir
Charge isopropyl alcohol (60 ml) and crude wet material Molnupiravir (11.8gm) into flask. Stir the mass at 70-80°C for 10-15 min to dissolve the material. Charge activated carbon (0.5 gm) and stir for 10 min at the same temperature. Filter the mass through hyflow bed into another RB Flask and wash the hyflow bed with isopropyl alcohol (10ml) and charge purified water (14 ml) into flask. Stir the mass for 70-80°C for 10 min to dissolve the material. Cool the mass to 25-30°C. Stir the mass for 45-60 min. Filter the material at 25-30°C and wash the material with isopropyl alcohol (3.0 ml). Dry the material at 60-65°C for 8 hours, obtain the 8.2 gm (85.0% of yield) of white colour material off white colour material with 99.88% of Purity.
,CLAIMS:WE CL AIM:

1. A process for the preparation of Molnupiravir (I), comprising the steps of;
a) Cytidine (5) is reacted with Aldehyde or Acetal and sulfuric acid (H2SO4) in presence of organic solvent to obtain the compound of formula (4),

Wherein Aldehyde is Formaldehyde, Benzaldehyde and 4-Anisaldehyde; Acetal is Benzaldehyde dimethyl acetal, Anisaldehyde dimethyl acetal, (1,1-Dimethoxyethyl)benzene;
wherein R is hydrogen, phenyl or substituted phenyl group;

b) The compound of formula (4) is reacted with isobutyric anhydride in presence of organic base and organic solvent to obtain the compound of formula (3),

c) The compound of formula (3) is reacted with hydroxylamine sulphate in presence of organic solvent to obtain the compound of formula (2),

d) The compound of formula (2) is deprotected with acid in presence of organic solvent to obtain Molnupiravir (I), and

e) Isolated the Molnupiravir (I).

2. The process as claimed in claim 1, wherein the organic solvent is selected from acetone, acetonitrile, ethyl acetate, water, isopropyl alcohol, methanol, ethanol, toluene, dimethyl sulfoxide (DMSO), dimethylformamide (DMF),isopropyl acetate and n-butyl acetate, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, dichloromethane (MDC), dichloroethane, carbon tetrachloride and chloroform and/or mixtures thereof.

3. The process as claimed in claim 1, wherein the organic base is selected from 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), Dimethylaminopyridine (DMAP), 5-diazabicyclo[4.3.0]non-5-ene (DBN), pyridine, triethylamine (TEA), Diisopropylethylamine (DIPEA), trimethylamine, diethylamine and N,N-dimethylaniline.

4. The process as claimed in claim 1, wherein the acid is selected from trifluoroacetic acid, formic acid, acetic acid and hydrochloric acid.

5. A novel compound of formula (2), (3) and (4).

wherein R is hydrogen, phenyl or substituted phenyl group;