Tenofovir alafenamide

Base Information

• Chemical Name: Tenofovir alafenamide
• CAS No.: 379270-37-8
• Deprecated CAS: 377091-31-1
• Molecular Formula: C21H29N6O5P
• Molecular Weight: 476.472
• UNII: EL9943AG5J
• DSSTox Substance ID: DTXSID50958941
• Wikipedia: Tenofovir_alafenamide
• Wikidata: Q22075912
• NCI Thesaurus Code: C148276
• RXCUI: 1721603
• Metabolomics Workbench ID: 152321
• ChEMBL ID: CHEMBL2107825
• Mol file: 379270-37-8.mol

Synonyms:GS-7340;GS-734003;L-alanine, N-((S)-(((1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy)methyl)phenoxyphosphinyl)-, 1-methylethyl ester;tenofovir alafenamide;vemlidy

Chemical Property of Tenofovir alafenamide

Chemical Property:

• Melting Point: >119°C (dec.)
• Boiling Point: 640.4±65.0 °C(Predicted)
• PKA: 4.21±0.10(Predicted)
• PSA: 153.29000
• Density: 1.39±0.1 g/cm3(Predicted)
• LogP: 3.94500
• Storage Temp.: 2-8°C(protect from light)
• Solubility.: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• XLogP3: 1.9
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 12
• Exact Mass: 476.19370504
• Heavy Atom Count: 33
• Complexity: 680

Purity/Quality:

99%+ ^*data from raw suppliers

TenofovirAlafenamide ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)OC(=O)C(C)NP(=O)(COC(C)CN1C=NC2=C(N=CN=C21)N)OC3=CC=CC=C3
• Isomeric SMILES: C[C@H](CN1C=NC2=C(N=CN=C21)N)OC[P@@](=O)(N[C@@H](C)C(=O)OC(C)C)OC3=CC=CC=C3
• Recent ClinicalTrials: Early Metabolic Effects of Dolutegravir or Tenofovir Alefenamide in Healthy Volunteers
• Recent EU Clinical Trials: The effect of tenofovir disoproxil fumarate (TDF) versus tenofovir alafenamide (TAF) on proximal small intestine – a potential mechanism to explain opposing effects on body weight
• Recent NIPH Clinical Trials: A Study of JNJ-73763989, JNJ-56136379, Nucleos(t)ide Analogs, and Pegylated Interferon Alpha-2a in Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection
• Description: Tenofovir Alafenamide (GS-7340) is a prodrug of tenofovir, which is a reverse transcriptase inhibitor, used to treat HIV and Hepatitis B.-Reverse Transcriptase inhibitor. It was developed by Gilead Sciences.?Compared to tenofovir disoproxil fumarate, tenofovir alafenamide has a greater antiviral activity and better distribution into lymphoid tissues. Tenofovir alafenamide fumarate is an oral phosphonoamidate prodrug of the reverse transcriptase inhibitor tenofovir. It was approved by the USFDA for the treatment of chronic hepatitis B virus infection with compensated liver disease. Tenofovir alafenamide fumarate was discovered and developed by Gilead as a potentially safer form of the previously approved tenofovir disoproxil fumarate (Viread).
• Uses: Tenofovir Alafenamide is a prodrug of Tenofovir (T018500), which is a reverse transcriptase inhibitor used to treat HIV and Hepatitis B. Antiviral.

Technology Process of Tenofovir alafenamide

There total 46 articles about Tenofovir alafenamide 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: 95.0%

isopropyl L-alanine (39825-33-7) + (((R)-1-(6-amino-9H-purin-9-yl)-1-methylethoxy)methyl)phenoxyphosphonyl chloride → (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)

Guidance literature:

(((R)-1-(6-amino-9H-purin-9-yl)-1-methylethoxy)methyl)phenoxyphosphonyl chloride; In Isopropyl acetate; at -20 ℃; for 1h;

isopropyl L-alanine; In Isopropyl acetate; at -20 - 20 ℃; for 2h;

Reference yield: 83.0%

isopropyl L-alanine (39825-33-7) + C15H17ClN5O3P → (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)

Guidance literature:

In dichloromethane; at -5 ℃; for 2h; Solvent;

Reference yield: 81.0%

9-[(R)-2-[[(S)-[[(S)-1-(isopropoxycarbonyl)ethyl]amino](phenoxy)phosphinyl]methoxy]propyl]adenine D-tartrate → (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)

Guidance literature:

With ammonium hydroxide; In dichloromethane; water; pH=8 - 9;

upstream raw materials:

isopropyl L-alanine

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester

tenofovir

phenol

Downstream raw materials:

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

tenofovir alafenamide fumarate

9-[(R)-2-[[(S)-[[(S)-1-(isopropoxycarbonyl)ethyl]amino]phenoxyphosphinyl]methoxy]propyl]adenine monomaleate

tenofovir alafenamide sesquifumarate

Refernces

• 1、 -. "Chemical resolution method of tenofovir alafenamide". Paragraph 0029; 0032-0037; 0039-0043. . Retrieved 2021/03/11.
• 2、 -. "NRTI THERAPIES". Page/Page column 71-72. . Retrieved 2020/07/14.