ChemicalBook CAS DataBase List Velpatasvir

Velpatasvir synthesis

11synthesis methods

Product Name:Velpatasvir
CAS Number:1377049-84-7
Molecular formula:C49H54N8O8
Molecular Weight:883

Velpatasvir, also known as GS-5816, is a potent and selective Hepatitis C virus NS5A inhibitor. GS-5816 has demonstrated pan-genotypic activity and a high barrier to resistance in HCV replicon assays. GS-5816 demonstrated pangenotypic antiviral activity in patients with genotype 1-4 HCV infection. It will be further evaluated in combination with other pangenotypic direct-acting antivirals to achieve the goal of developing a well-tolerated, highly effective treatment for all HCV genotypes. Synthetic Description Reference: Reddy, Bandi Parthasaradhi; Reddy, Kura Rathnakar; Narasingam, Mogili; Krishna, Bandi Vamsi. Process for the preparation of velpatasvir. Assignee Hetero Research Foundation, India. IN 201641022433. (2018). Synthetic Description Fu, Shaojun; Huang, Chengjun; Ren, Yi; Cai, Huirong; Wang, Qiong; Yang, Xin'an; Li, Wei. Preparation of velpatasvir and its derivative. Assignee Shanghai ForeFront Pharmceutical Co., Ltd., Peop. Rep. China. WO 2018153380. (2018) Synthetic Description Wang, Jianming. Preparation of amino acid derivatives as anti-hepatitis C virus agents. Assignee Beijing Meibeita Pharmaceutical Research Co., Ltd., Peop. Rep. China. CN 107540679. (2018).

Synthetic Routes

ROUTE 1

ROUTE 2

ROUTE 3

Reference: Reddy, Bandi Parthasaradhi; Reddy, Kura Rathnakar; Narasingam, Mogili; Krishna, Bandi Vamsi. Process for the preparation of velpatasvir. Assignee Hetero Research Foundation, India. IN 201641022433. (2018).

1377604-63-1 Synthesis

1377604-63-1
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1377049-84-7
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Yield:1377049-84-7 89%

Reaction Conditions:

with acetic acid;2,3-dicyano-5,6-dichloro-p-benzoquinone in tetrahydrofuran at 0 - 5;Inert atmosphere;

Steps:

1.5-3.5 Preparation of Velpatasvir:
Under the protection of nitrogen, add intermediate VP4 (23.3g, 26mmol, 1.0eq), 200mL of tetrahydrofuran to a 500mL reaction flask, stir to dissolve, cool to 0-5°C, add glacial acetic acid, and then add 50mL of DDQ tetrahydrofuran solution (8.9 g, 39 mmol, 1.5 eq). After the drop, the reaction was performed at 0-5°C, and the reaction was monitored by TLC. After the reaction was completed, 10% sodium hydroxide solution was added dropwise to adjust the pH to near neutral. 150 mL of water and 300 mL of dichloromethane were added, stirred, and allowed to stand for separation; the aqueous layer was extracted with dichloromethane (200 mL×3), and the organic phases were combined , Washed with saturated aqueous sodium chloride solution (200 mL×1), dried over anhydrous sodium sulfate, filtered with suction, and the filtrate was concentrated under reduced pressure to obtain a crude solid product. The crude product was recrystallized with 200 mL of isopropanol and water (2:1) to obtain 20.7 g of Velpatasvir solid product. Yield: 89%.

References:

Nantong Changyou Pharmaceutical Technology Co., Ltd.;Li Zebiao;Shen Minzhe;Ding Hongping;Pan Jing;Zou Lin CN110981879, 2020, A Location in patent:Page/Page column 6-8; 10

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1378391-45-7 Synthesis