Tenofovir Alafenamide Fumarate

Base Information

• Chemical Name: Tenofovir Alafenamide Fumarate
• CAS No.: 1392275-56-7
• Molecular Formula: C₄H₄O₄*C₂₁H₂₉N₆O₅P
• Molecular Weight: 592.546
• Mol file: 1392275-56-7.mol

Synonyms:L-Alanine,N-[(S)-[[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]phenoxyphosphinyl]-, 1-methylethyl ester, (2E)-2-butenedioate (2:1);N-[(S)-[[(1R)-2-(6-Amino-9H-purin-9-yl)-1-methylethoxy]methyl]phenoxyphosphinyl]-L-alanine 1-methylethyl ester (2E)-2-butenedioate (2:1);GS-7340 (hemifumarate);(S)-Isopropyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate fumarate(2:1);(R)-isopropyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate fumarate;N-[(S)-[[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]phenoxyphosphinyl]-, 1-methylethyl ester

Chemical Property of Tenofovir Alafenamide Fumarate

Chemical Property:

• PSA: 381.18000
• LogP: 7.60180
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature

Purity/Quality:

99% ,99.9%, ^*data from raw suppliers

TenofovirAlafenamideHemifumarate >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Tenofovir alafenamide hemifumarate is an investigational oral prodrug of Tenofovir. Tenofovir is a HIV-1 nucleotide reverse transcriptase inhibitor.
• Uses: Tenofovir alafenamide hemifumarate is a newer, more effective prodrug used in combination with FTC that has recently been approved for the prevention of HIV transmission through the rectum. It is used to treat chronic hepatitis B virus (HBV) infection in adults with compensated liver disease.

Technology Process of Tenofovir Alafenamide Fumarate

There total 23 articles about Tenofovir Alafenamide Fumarate 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: 92.0%

(2E)-but-2-enedioic acid (110-17-8,26099-09-2) + (S)-isopropyl-2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate (379270-37-8,2053424-88-5,379270-36-7) → (S)-isopropyl-2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate hemifumarate (1392275-56-7)

Guidance literature:

In acetonitrile; at 55 ℃; for 2h;

DOI:10.2174/1570178614666170907115708

Reference yield:

tenofovir (147127-20-6) → tenofovir alafenamide hemifumarate (1392275-56-7)

Guidance literature:

Multi-step reaction with 3 steps

1.1: dmap; triethylamine / 1-methyl-pyrrolidin-2-one; cyclohexane / 40 h / 80 °C

2.1: thionyl chloride; N,N-dimethyl-formamide / toluene; acetonitrile / 26.25 h / 20 - 70 °C

3.1: chloro-trimethyl-silane / dichloromethane / 1 h / 20 °C

3.2: 5 h / -25 - 3 °C

3.3: Reflux

With dmap; chloro-trimethyl-silane; thionyl chloride; triethylamine; N,N-dimethyl-formamide; In 1-methyl-pyrrolidin-2-one; dichloromethane; cyclohexane; toluene; acetonitrile;

Reference yield:

(2E)-but-2-enedioic acid (110-17-8,26099-09-2) + N-[(R)-[[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]phenoxyphosphonyl]-L-alanine-1-methylethyl ester (383365-04-6,2053424-88-5,379270-36-7) → 9-[(R)-2-[[(R)-1-[[(S)-(isopropoxycarbonyl)ethyl]amino]phenoxyphosphinyl]methoxy]propyl]adenine monofumarate (1392275-56-7)

Guidance literature:

In acetonitrile; Heating;

DOI:10.1081/NCN-100002338

upstream raw materials:

(2E)-but-2-enedioic acid

N-[(R)-[[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]phenoxyphosphonyl]-L-alanine-1-methylethyl ester

isopropyl L-alanine

tenofovir

Downstream raw materials:

(S)-isopropyl-2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate

Refernces

• 1、 Gan, Yongjun,Ran, Kerui,Xie, Hongmeng,Yang, Bin. "Efficient synthesis and resolution of tenofovir alafenamide". . p. 10 - 14. Retrieved 2018.
• 2、 -. "CRYSTAL FORM OF TENOFOVIR ALAFENAMIDE SALT, PREPARATION METHOD AND USE THEREOF". Paragraph 0039; 0040; 0041; 0042; 0043; 0044; 0045-0053. . Retrieved 2019/04/18.