N-((R)-(((1R)-2-(6-Amino-9H-purin-9-yl)-1-methylethoxy)methyl)phenoxyphosphinyl)-L-alanine 1-methylethyl ester

Base Information

• Chemical Name: N-((R)-(((1R)-2-(6-Amino-9H-purin-9-yl)-1-methylethoxy)methyl)phenoxyphosphinyl)-L-alanine 1-methylethyl ester
• CAS No.: 383365-04-6
• Molecular Formula: C21H29N6O5P
• Molecular Weight: 476.472
• UNII: J4414G3BUK
• Wikipedia: Tenofovir_alafenamide
• Mol file: 383365-04-6.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 N-((R)-(((1R)-2-(6-Amino-9H-purin-9-yl)-1-methylethoxy)methyl)phenoxyphosphinyl)-L-alanine 1-methylethyl ester

Chemical Property:

• 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
• 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:

98%,99%, ^*data from raw suppliers

N-[(R)-[[(1R)-2-(6-Amino-9H-purin-9-yl)-1-methylethoxy]methyl]phenoxyphosphinyl]-L-alanine1-MethylethylEster ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

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: A Phase 1b Study Assessing GS-7340 in Treatment-Naive Adults With Chronic Hepatitis B
• Recent EU Clinical Trials: A Phase 2a, Open-Label Study to Evaluate the Safety and Efficacy of Selgantolimod (SLGN)-Containing Combination Therapies for the Treatment of Chronic Hepatitis B (CHB)
• Uses: (S)-Isopropyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate is an isomer of Tenofovir Alafenamide (T018555), is a prodrug of Tenofovir (T018500).

Technology Process of N-((R)-(((1R)-2-(6-Amino-9H-purin-9-yl)-1-methylethoxy)methyl)phenoxyphosphinyl)-L-alanine 1-methylethyl ester

There total 9 articles about N-((R)-(((1R)-2-(6-Amino-9H-purin-9-yl)-1-methylethoxy)methyl)phenoxyphosphinyl)-L-alanine 1-methylethyl ester 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: 81.0%

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

Guidance literature:

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

Reference yield:

isopropyl L-alanine (39825-33-7) + ((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester (379270-35-6) → (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) + 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)

Guidance literature:

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester; With thionyl chloride; In acetonitrile; at 75 - 80 ℃;

isopropyl L-alanine; In dichloromethane; at -18 ℃; for 1h;

DOI:10.1081/NCN-100002338

Reference yield:

tenofovir (147127-20-6) + phenol (108-95-2,27073-41-2) → (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) + 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)

Guidance literature:

Multi-step reaction with 2 steps

1.1: N-ethyl-N,N-diisopropylamine; dicyclohexyl-carbodiimide / 16 h / 60 - 100 °C / Large scale

2.1: thionyl chloride / acetonitrile / 2 h / 75 - 85 °C / Large scale

2.2: 3 h / -25 - 35 °C / Large scale

With thionyl chloride; N-ethyl-N,N-diisopropylamine; dicyclohexyl-carbodiimide; In acetonitrile;

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

(2S)-isopropyl2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate

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

Refernces

• 1、 -. "Preparation method and application for high-purity tenofovir alafenamide fumarate intermediate". Paragraph 0044; 0045; 0046; 0047; 0048; 0049; 0050-0064. . Retrieved 2017/08/28.
• 2、 -. "AN EFFICIENT PROCESS FOR SEPARATION OF DIASTEREOMERS OF 9-[(R)-2-[[(R,S)-[[(S)-1-(ISOPROPOXYCARBONYL)ETHYL]AMINO]-PHENOXYPHOSPHINYL] METHOXY]PROPYL]ADENINE". Page/Page column 15. . Retrieved 2015/01/06.