Sofosbuvir, also known as PSI-7977 and GS7977 (brand names Sovaldi and Virunon), is a drug used for hepatitis C virus (HCV) infection, with a high cure rate. It inhibits the RNA polymerase that the hepatitis C virus uses to replicate its RNA. It was discovered at Pharmasset and developed by Gilead Sciences. Sofosbuvir is a component of the first all-oral, interferon-free regimen approved for treating chronic Hepatitis C. In 2013, the FDA approved sofosbuvir in combination with ribavirin (RBV) for oral dual therapy of HCV genotypes 2 and 3, and for triple therapy with injected pegylated interferon (pegIFN) and RBV for treatment-naive patients with HCV genotypes 1 and 4. Synthetic Description Reference: Wilhelm, Thorsten; Schoene, Olga. Synthesis of sofosbuvir nucleoside phosphoramidate via hydride reduction of ketone. WO 2018134343. (Sandoz AG, Switz) Synthetic Description Reference: Siripragada, Mahender Rao; Kondepati, Venkata Ramana; Dhameliya, Dharmesh; Raval, Prashant; Domadiya, Vipul; Badam, Sreemannarayana; Pirzada, Azim. Process for the preparation of (sp)-sofosbuvir and intermediates thereof. WO 2018025195. (Process for the preparation of (sp)-sofosbuvir and intermediates thereof) Synthetic Description Reference: Reddy, Srinivas Reddy Desi; Velivela, Srinivas Rao. An improved process for the preparation of sofosbuvir. WO 2018015821. (Optimus Drugs (P) Limited, India) Synthetic Description Reference: Gaboardi, Mauro; Pallanza, Giuseppe; Baratella, Marco; Castaldi, Graziano; Castaldi, Marta. Chemoenzymic preparation of sofosbuvir involving a lipase catalyzed regioselective deacetylation. WO 2017144423. (HC-Pharma AG, Switz.) Synthetic Description Reference: Matta, Hari Babu; Sharma, Atul; Shaikh, Shakir Shabbir; Sharma, Kapil; Saini, Anil; Khanna, Mahavir Singh; Prasad, Mohan. Process for the preparation of pure sofosbuvir via coupling reaction as anti-hepatitis C antiviral agent. WO 2017093973. (Sun Pharmaceutical Industries Limited, India) Synthetic Description Reference: Kosik, Kamil; Sagol, Karol; Godzisz, Mateusz. Process for the preparation of sofosbuvir as pharmaceutical agent. EP 3133062. (Zaklady Farmaceutyczne Polpharma SA, Pol.) Synthetic Description Reference: Kosik, Kamil; Sagol, Karol; Godzisz, Mateusz. Process for the preparation of sofosbuvir as pharmaceutical agent. WO 2017029397. (Zaklady Farmaceutyczne Polpharma SA, Pol. 2017) Synthetic Description Reference: Rampalli, Sriram; Upalla, Lav Kumar; Dhkarapu, Veera Venkatarao; Krishna, Dasari Gopal; Chaturvedi, Akshay Kant. An improved process for the preparation of sofosbuvir. WO 2017009746. (Shilpa Medicare Limited, India) Synthetic Description Reference: Schoene, Olga; Wilhelm, Thorsten. Synthesis of phosphoramidates. WO 2016207194. (Sandoz AG, Switz.) Synthetic Description Reference: Kansal, Vinod Kumar; Mistry, Dhirenkumar Natvarial; Achanta, Srinivas; Ariyamuthu, Sundaraselvan; Goswami, Miteshgir Kanchangir; Yazali, Venkata Subbarao. Improved processes for the preparation of sofosbuvir and intermediates thereof via coupling reaction of nucleosides with amino acid. WO 2016196735. (Teva Pharmaceuticals International GmbH, Switz.; Teva Pharmaceuticals USA, Inc. 2016) Synthetic Description Reference: Wilhelm, Thorsten; Schoene, Olga; Spitzenstaetter, Hans-Peter. Selective process for synthesis of nucleoside phosphoramidates via coupling reaction. WO 2016189040. (Sandoz AG, Switz.)

• ROUTE 1



Reference: Wilhelm, Thorsten; Schoene, Olga. Synthesis of sofosbuvir nucleoside phosphoramidate via hydride reduction of ketone. WO 2018134343. (Sandoz AG, Switz)

• ROUTE 2



Reference: Siripragada, Mahender Rao; Kondepati, Venkata Ramana; Dhameliya, Dharmesh; Raval, Prashant; Domadiya, Vipul; Badam, Sreemannarayana; Pirzada, Azim. Process for the preparation of (sp)-sofosbuvir and intermediates thereof. WO 2018025195. (Process for the preparation of (sp)-sofosbuvir and intermediates thereof)

• ROUTE 3



Reference: Reddy, Srinivas Reddy Desi; Velivela, Srinivas Rao. An improved process for the preparation of sofosbuvir. WO 2018015821. (Optimus Drugs (P) Limited, India)

• ROUTE 4



Reference: Gaboardi, Mauro; Pallanza, Giuseppe; Baratella, Marco; Castaldi, Graziano; Castaldi, Marta. Chemoenzymic preparation of sofosbuvir involving a lipase catalyzed regioselective deacetylation. WO 2017144423. (HC-Pharma AG, Switz.)

• ROUTE 5



Reference: Matta, Hari Babu; Sharma, Atul; Shaikh, Shakir Shabbir; Sharma, Kapil; Saini, Anil; Khanna, Mahavir Singh; Prasad, Mohan. Process for the preparation of pure sofosbuvir via coupling reaction as anti-hepatitis C antiviral agent. WO 2017093973. (Sun Pharmaceutical Industries Limited, India)

• ROUTE 6



Reference: Kosik, Kamil; Sagol, Karol; Godzisz, Mateusz. Process for the preparation of sofosbuvir as pharmaceutical agent. EP 3133062. (Zaklady Farmaceutyczne Polpharma SA, Pol.)

• ROUTE 7



Reference: Kosik, Kamil; Sagol, Karol; Godzisz, Mateusz. Process for the preparation of sofosbuvir as pharmaceutical agent. WO 2017029397. (Zaklady Farmaceutyczne Polpharma SA, Pol. 2017)

• ROUTE 8



Reference: Rampalli, Sriram; Upalla, Lav Kumar; Dhkarapu, Veera Venkatarao; Krishna, Dasari Gopal; Chaturvedi, Akshay Kant. An improved process for the preparation of sofosbuvir. WO 2017009746. (Shilpa Medicare Limited, India)

• ROUTE 9



Reference: Schoene, Olga; Wilhelm, Thorsten. Synthesis of phosphoramidates. WO 2016207194. (Sandoz AG, Switz.)

• ROUTE 10



Reference: Kansal, Vinod Kumar; Mistry, Dhirenkumar Natvarial; Achanta, Srinivas; Ariyamuthu, Sundaraselvan; Goswami, Miteshgir Kanchangir; Yazali, Venkata Subbarao. Improved processes for the preparation of sofosbuvir and intermediates thereof via coupling reaction of nucleosides with amino acid. WO 2016196735. (Teva Pharmaceuticals International GmbH, Switz.; Teva Pharmaceuticals USA, Inc. 2016)

• ROUTE 11



Reference: Wilhelm, Thorsten; Schoene, Olga; Spitzenstaetter, Hans-Peter. Selective process for synthesis of nucleoside phosphoramidates via coupling reaction. WO 2016189040. (Sandoz AG, Switz.)