GS9857

Base Information

• Chemical Name: GS9857
• CAS No.: 1535212-07-7
• Molecular Formula: C40H52F4N6O9S
• Molecular Weight: 868.947
• Mol file: 1535212-07-7.mol

Synonyms:GS9857;Voxilaprevir

Chemical Property of GS9857

Chemical Property:

• PKA: 4.46±0.40(Predicted)
• PSA: 203.60000
• Density: 1.42±0.1 g/cm3(Predicted)
• LogP: 7.08580

Purity/Quality:

99%, ^*data from raw suppliers

Voxilaprevir >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Uses: Voxilaprevir(GS9857) is a hepatitis C virus (HCV) nonstructural (NS) protein 3/4A protease inhibitor (by Gilead) that is used in combination with sofosbuvir and velpatasvir. The combination has the trade name Vosevi and received a positive opinion from the European Committee for Medicinal Products for Human Use in June 2017. On 18 July 2017, Vosevi was approved by the US Food and Drug Administration. Voxilaprevir is a new chemical entity recently approved in a fixed-dose combination with sofosbuvir1,2 and velpatasvir.3 Like glecaprevir and grazoprevir, voxilaprevir inhibits the NS3/4A protease involved in viral replication. Sofosbuvir is an NS5B nucleotide polymerase inhibitor and velpatasvir is an NS5A inhibitor.

Technology Process of GS9857

There total 20 articles about GS9857 which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield:

C31H40F2N4O7 (1535212-06-6) + C9H14F2N2O3S*ClH (1360828-80-3) → (1aR,5S,8S,9S,10R,22aR)-5-tert-butyl-N-[(1 R,2R)-2-(difluoromethyl)-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]-9-ethyl-18,18-difluoro-14-methoxy-3,6-dioxo-1,1a,3,4,5,6,9,1 0,18,19,20,21,22,22a-tetradecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoxaline-8-carboxamide (1535212-07-7)

Guidance literature:

With dmap; N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20 ℃; for 0.666667h;

Reference yield:

(2S,3S,4R)-di-tert-butyl 3-ethyl-4-hydroxypyrrolidine-1,2-dicarboxylate → (1aR,5S,8S,9S,10R,22aR)-5-tert-butyl-N-[(1 R,2R)-2-(difluoromethyl)-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]-9-ethyl-18,18-difluoro-14-methoxy-3,6-dioxo-1,1a,3,4,5,6,9,1 0,18,19,20,21,22,22a-tetradecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoxaline-8-carboxamide (1535212-07-7)

Guidance literature:

Multi-step reaction with 6 steps

1.1: caesium carbonate / acetonitrile / 36 h / 85 °C

1.2: 2.5 h / 20 °C

2.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 20 °C

3.1: 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(iso-propoxy)-5-(N,N-dimethylaminosulfonyl)phenyl]methylene ruthenium(II) dichloride / 1,2-dichloro-ethane / 1.33 h / 100 °C / Inert atmosphere

4.1: palladium 10% on activated carbon; hydrogen / ethanol / 2.5 h / 760.05 Torr

5.1: trifluoroacetic acid / dichloromethane / 3 h / 20 °C

6.1: N-ethyl-N,N-diisopropylamine; HATU; dmap / N,N-dimethyl-formamide / 0.67 h / 20 °C

With dmap; 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(iso-propoxy)-5-(N,N-dimethylaminosulfonyl)phenyl]methylene ruthenium(II) dichloride; palladium 10% on activated carbon; hydrogen; caesium carbonate; N-ethyl-N,N-diisopropylamine; HATU; trifluoroacetic acid; In ethanol; dichloromethane; 1,2-dichloro-ethane; N,N-dimethyl-formamide; acetonitrile;

Reference yield:

C37H50F2N4O7 (1535212-03-3) → (1aR,5S,8S,9S,10R,22aR)-5-tert-butyl-N-[(1 R,2R)-2-(difluoromethyl)-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]-9-ethyl-18,18-difluoro-14-methoxy-3,6-dioxo-1,1a,3,4,5,6,9,1 0,18,19,20,21,22,22a-tetradecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoxaline-8-carboxamide (1535212-07-7)

Guidance literature:

Multi-step reaction with 4 steps

1: 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(iso-propoxy)-5-(N,N-dimethylaminosulfonyl)phenyl]methylene ruthenium(II) dichloride / 1,2-dichloro-ethane / 1.33 h / 100 °C / Inert atmosphere

2: palladium 10% on activated carbon; hydrogen / ethanol / 2.5 h / 760.05 Torr

3: trifluoroacetic acid / dichloromethane / 3 h / 20 °C

4: N-ethyl-N,N-diisopropylamine; HATU; dmap / N,N-dimethyl-formamide / 0.67 h / 20 °C

With dmap; 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(iso-propoxy)-5-(N,N-dimethylaminosulfonyl)phenyl]methylene ruthenium(II) dichloride; palladium 10% on activated carbon; hydrogen; N-ethyl-N,N-diisopropylamine; HATU; trifluoroacetic acid; In ethanol; dichloromethane; 1,2-dichloro-ethane; N,N-dimethyl-formamide;

upstream raw materials:

methyl 3-methyl-N-({[(1R,2R)-2-pent-4-en-1-ylcyclopropyl]oxy}carbonyl)-L-valinate

3-methyl-N-({[(1R,2R)-2-pent-4-en-1-ylcyclopropyl]oxy}carbonyl)-L-valine

C₁₄H₂₃NO₅

C₁₄H₂₅NO₅

Refernces

• 1、 -. "INHIBITORS OF HEPATITIS C VIRUS". . . Retrieved 2014/01/18.