L-Alanine, N-[(S)-hydroxyphenoxyphosphinyl]-, 1-Methylethyl ester, (P→3'),(P'→5')-diester with (2'R)-2'-deoxy-2'-fluoro-2'-Methyluridine

Base Information

• Chemical Name: L-Alanine, N-[(S)-hydroxyphenoxyphosphinyl]-, 1-Methylethyl ester, (P→3'),(P'→5')-diester with (2'R)-2'-deoxy-2'-fluoro-2'-Methyluridine
• CAS No.: 1337482-17-3
• Molecular Formula: C₃₄H₄₅FN₄O₁₃P₂
• Molecular Weight: 798.696
• Mol file: 1337482-17-3.mol

Synonyms:

Chemical Property of L-Alanine, N-[(S)-hydroxyphenoxyphosphinyl]-, 1-Methylethyl ester, (P→3'),(P'→5')-diester with (2'R)-2'-deoxy-2'-fluoro-2'-Methyluridine

Chemical Property:

• PKA: 9.39±0.10(Predicted)
• Density: 1.37±0.1 g/cm3(Predicted)

Purity/Quality:

NLT 98% ^*data from raw suppliers

Sofosbuvir3'',5''-Bis-(S)-phosphate ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Uses: Sofosbuvir Impurity Sofosbuvir 3'',5''-Bis-(S)-phosphate is an impurity of PSI-7977 (P839640), a prodrug that is metabolized to the active antiviral agent 2''-deoxy-2''-α-fluoro-β-C-methyluridine-5''-monophosphate and is currently being investigated in phase 3 clinical trials for the treatment of hepatitis C. Studies have profiled PSI-7977 as a nucleotide inhibitor of hepatitis C virus, exerting selective inhibitory effects towards HCV NS5B polymerase.

Technology Process of L-Alanine, N-[(S)-hydroxyphenoxyphosphinyl]-, 1-Methylethyl ester, (P→3'),(P'→5')-diester with (2'R)-2'-deoxy-2'-fluoro-2'-Methyluridine

There total 4 articles about L-Alanine, N-[(S)-hydroxyphenoxyphosphinyl]-, 1-Methylethyl ester, (P→3'),(P'→5')-diester with (2'R)-2'-deoxy-2'-fluoro-2'-Methyluridine 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:

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + 2'-deoxy-2'-fluoro-2'-methyluridine (863329-66-2,2041584-99-8) → sofosbuvir (1064684-44-1,1496552-16-9) + C34H45FN4O13P2 (1337482-17-3)

Guidance literature:

With tert-butylmagnesium chloride; In tetrahydrofuran; at 20 ℃; for 17.5h; Inert atmosphere; Molecular sieve;

Reference yield:

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + 2'-deoxy-2'-fluoro-2'-methyluridine (863329-66-2,2041584-99-8) → sofosbuvir (1190307-88-0,1496552-16-9) + (S)-2-{(R)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-ylmethoxy](phenoxy)phosphorylamino}propionic acid isopropyl ester (1190308-01-0,1496552-16-9) + C34H45FN4O13P2 (1337482-17-3)

Guidance literature:

With 1-methyl-1H-imidazole; In tetrahydrofuran; at 0 - 20 ℃; for 2.75h; Reagent/catalyst; Time; Solvent; Optical yield = 18 %de; Inert atmosphere;

Reference yield:

2'-deoxy-2'-fluoro-2'-methyluridine (863329-66-2,2041584-99-8) + (S)-2-[(S)-((2,3,4,5,6-pentafluorophenoxy)(phenoxy)phosphoryl)amino]propionic acid isopropyl ester (1334513-02-8,1627824-09-2) → sofosbuvir (1190307-88-0,1496552-16-9) + (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-2-((((S)-(((S)-1-isopropoxy-1-oxopropan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)-4-methyltetrahydrofuran-3-yl)oxy)(phenoxy)phosphoryl)amino)propanoate (1337482-17-3)

Guidance literature:

With pyridine; dimethylaluminum chloride; In hexane; at 0 - 20 ℃; for 20h; Reagent/catalyst; diastereoselective reaction; Inert atmosphere;

DOI:10.1021/acs.orglett.7b00469

upstream raw materials:

phenyl(isopropoxy-L-alaninyl) phosphorochloridate

2'-deoxy-2'-fluoro-2'-methyluridine

(S)-2-[(S)-((2,3,4,5,6-pentafluorophenoxy)(phenoxy)phosphoryl)amino]propionic acid isopropyl ester

Refernces

• 1、 -. "SELECTIVE PROCESS FOR SYNTHESIS OF NUCLEOSIDE PHOSPHORAMIDATES". Page/Page column 130. . Retrieved 2016/12/22.