Velpatasvir intermediate

Base Information

• Chemical Name: Velpatasvir intermediate
• CAS No.: 1378391-43-5
• Molecular Formula: C44H55N3O13
• Molecular Weight: 833.933
• Mol file: 1378391-43-5.mol

Synonyms:VP N-3;(2R,4R)-1-tert-butyl 2-(2-(9-((2S,5S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carbonyloxy)-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-3-yl)-2-oxoethyl) 4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate;Velpatasvir intermediate N-4;1-tert-Butyl 2-[2-[9-[[[(2S,5S)-1-[(S)-2-(methoxycarbonylamino)-3-methylbutanoyl]-5-methylpyrrolidin-2-yl]carbonyl]oxy]-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-3-yl]-2-oxoethyl] (2S,4S)-4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate;Velpatasvir N-3

Chemical Property of Velpatasvir intermediate

Chemical Property:

• PSA: 193.38000
• LogP: 5.31140

Purity/Quality:

98.0%Min ^*data from raw suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

Technology Process of Velpatasvir intermediate

There total 19 articles about Velpatasvir intermediate 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: 90.0%

(2S,5S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carboxylic acid (1335316-40-9) + (2S,4S)-2-(2-(9-bromo-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-3-yl)-2-oxoethyl) 1-tert-butyl 4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate (1378391-42-4) → (2R,4R)-1-tert-butyl 2-(2-(9-((2S,5S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carbonyloxy)-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-3-yl)-2-oxoethyl) 4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate (1378391-43-5)

Guidance literature:

With caesium carbonate; In 2-methyltetrahydrofuran; at 50 ℃; for 20h;

Reference yield: 86.0%

(2S,4S)-N-(tert-butyloxycarbonyl)-4-(methoxymethyl)-pyrrolidine-2-carboxylic acid (1378388-16-9) + 9-bromo-3-(2-bromoacetyl)-10,11-dihydro-5H-benzo[d]naphtho[2,3-b]pyran-8(9H)-one (1438383-89-1) + C13H22N2O5 → (2R,4R)-1-tert-butyl 2-(2-(9-((2S,5S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carbonyloxy)-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-3-yl)-2-oxoethyl) 4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate (1378391-43-5)

Guidance literature:

(2S,4S)-N-(tert-butyloxycarbonyl)-4-(methoxymethyl)-pyrrolidine-2-carboxylic acid; 9-bromo-3-(2-bromoacetyl)-10,11-dihydro-5H-benzo[d]naphtho[2,3-b]pyran-8(9H)-one; With caesium carbonate; In tetrahydrofuran; at 50 - 55 ℃;

C₁₃H₂₂N₂O₅; In tetrahydrofuran; at 50 - 55 ℃;

Reference yield:

7-hydroxy-1-tetralone (22009-38-7) → (2R,4R)-1-tert-butyl 2-(2-(9-((2S,5S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carbonyloxy)-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-3-yl)-2-oxoethyl) 4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate (1378391-43-5)

Guidance literature:

Multi-step reaction with 7 steps

1.1: potassium carbonate / N,N-dimethyl-formamide / 18 h / 20 °C

2.1: Trimethylacetic acid; potassium carbonate; palladium(II) trimethylacetate; P(p-C₆H₄F)3 / N,N-dimethyl acetamide / 24 h / 60 °C / Inert atmosphere

3.1: palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium carbonate / propan-1-ol / 5.5 h / Inert atmosphere; Reflux

4.1: N-Bromosuccinimide / water; tetrahydrofuran; dimethyl sulfoxide / 0.55 h / 20 °C

4.2: 15 h / 20 °C

5.1: caesium carbonate / 4 h / 20 °C

6.1: pyridinium hydrobromide perbromide / dichloromethane; methanol / 1.75 h / 20 °C

7.1: caesium carbonate / 20 h / 50 °C

With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; N-Bromosuccinimide; pyridinium hydrobromide perbromide; palladium(II) trimethylacetate; palladium diacetate; potassium carbonate; caesium carbonate; P(p-C₆H₄F)3; Trimethylacetic acid; In tetrahydrofuran; methanol; propan-1-ol; dichloromethane; N,N-dimethyl acetamide; water; dimethyl sulfoxide; N,N-dimethyl-formamide;

upstream raw materials:

3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one

(2S,5S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carboxylic acid

(2S,4S)-2-(2-(9-bromo-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-3-yl)-2-oxoethyl) 1-tert-butyl 4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate

(2S,5S)-ethyl 5-methylpyrrolidine-2-carboxylate 2,2,2-trifluoro acetate salt

Downstream raw materials:

tert-butyl (2S,4S)-2-[5-(2-{(2S,5S)-1-[N-(methoxycarbonyl)-L-valyl]-5-methylpyrrolidin-2-yl}-1,4,5,11-tetrahydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl)-1H-imidazol-2-yl]-4-(methoxymethyl)pyrrolidine-1-carboxylate

tert-butyl (2S,4S)-2-[5-(2-{(2S,5S)-1-[N-(methoxycarbonyl)-L-valyl]-5-methylpyrrolidin-2-yl}-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl)-1H-imidazol-2-yl]-4-(methoxymethyl)pyrrolidine-1-carboxylate

methyl {(1R)-2-[(2S,4S)-2-(5-{2-[(2S,5S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}-5-methylpyrrolidin-2-yl]-1,4,5,11-tetrahydroisochromeno[4',3':6,7]naphtho[1,2-d]imidazol-9-yl}-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl]-2-oxo-1-phenylethyl}carbamate

methyl {(2S)-1-[(2S,5S)-2-(9-{2-[(2S,4S)-1-{(2R)-2-[(methoxycarbonyl)amino]-2-phenylacetyl}-4-(methoxymethyl)pyrrolidin-2-yl]-1H-imidazol-5-yl}-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl)-5-methylpyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate

Refernces

• 1、 -. "CONDENSED IMIDAZOLYLIMIDAZOLES AS ANTIVIRAL COMPOUNDS". . . Retrieved 2013/06/05.