383365-04-6

Basic information

• Product Name: Tenofovir Related Compound 6
• Synonyms: Tenofovir Related Compound 6;Tenofovir Impurity 6;Tenofovir Alafenamide Impurity 3;Tenofovir Alafenamide Impurity E;isopropyl (((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)-L-alaninate;TAF Impurity E;L-Alanine,N-[(R)-[[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]phenoxyphosphinyl]-, 1-methylethyl ester;(S)-isopropyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate
• CAS NO: 383365-04-6
• Molecular Formula: C₂₁H₂₉N₆O₅P
• Molecular Weight: 476.465921
• Mol File: 383365-04-6.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 640.4±65.0 °C(Predicted)
• Appearance: /
• Density: 1.39±0.1 g/cm3(Predicted)
• PKA: 4.21±0.10(Predicted)
• CAS DataBase Reference: Tenofovir Related Compound 6(CAS DataBase Reference)
• NIST Chemistry Reference: Tenofovir Related Compound 6(383365-04-6)
• EPA Substance Registry System: Tenofovir Related Compound 6(383365-04-6)

Safety Data

• Hazardous Substances Data: 383365-04-6(Hazardous Substances Data)

Usage

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).

Upstream product

• 39613-92-8 alanine isopropyl ester hydrochloride 
• 379270-35-6 ((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester 
• 39825-33-7 isopropyl L-alanine 
• 108-95-2 phenol 
• 147127-20-6 tenofovir 

Downstream Products

• 1392275-56-7 (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 tenofovir alafenamide fumarate 
• 2053424-88-5 (2S)-isopropyl2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate 
• 379270-37-8 (S)-isopropyl-2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate 
• 1392275-56-7 9-[(R)-2-[[(R)-1-[[(S)-(isopropoxycarbonyl)ethyl]amino]phenoxyphosphinyl]methoxy]propyl]adenine monofumarate 

Relevant articles and documents

Industrial synthesis method of propofovir disoproxil fumarate

The invention provides a preparation process of propofovir disoproxil fumarate, which is short in production period, simple to operate and suitable for industrial production, and the high-purity propofovir disoproxil fumarate is prepared by taking the propofovir disoproxil fumarate as a starting material through special phosphorus chiral atom synthesis, purification and separation. The purity of the prepared propofovir disoproxil fumarate is greater than 99.90%, the diastereoisomer is less than 0.15%, the content of other single impurities is less than 0.10%, and the method has high commercialscale production value.

Preparation method of tenofovir alafenamide

The invention discloses a preparation method of tenofovir alafenamide. The preparation method comprises the following specific steps: carrying out heating reaction on PMPA and a chlorination agent to obtain PMPA-2Cl; enabling the PMPA-2Cl to react with phenol and L-alanine isopropyl ester in sequence through a one pot method to obtain TAF-RS; purifying the TAF-RS to obtain the tenofovir alafenamide, wherein the chlorination agent is one of sulfoxide chloride, phosphorus chloride, phosphorus pentachloride and oxalyl chloride; the one pot method is to enable the PMPA-2Cl to react with the phenol first in an organic solvent under a condition of -30 to -20 DEG C under existence of organic alkali, and then add the L-alanine isopropyl ester for reaction. According to the synthesis process provided by the invention, the complicated operation process is avoided, the reaction steps are simplified; furthermore, as the raw materials are readily available, the reactions are mild, and the cost is relatively low, the preparation method is suitable for industrial production.

Practical synthesis, separation, and stereochemical assignment of the PMPA pro-drug GS-7340

The practical synthesis of a mixed phenoxy-amidate derivative of PMPA with high oral bioavailability and favorable pharmacokinetics is described. The non-stereoselective synthetic route produces a 1:1 mixture of two diastereomers at phosphorous. Simulated moving bed chromatography using Chiralpak AS enabled kilo-scale isolation of the more potent diastereomer (GS-7340). The GS-7340 phosphorous chiral center was found to be (S) by X-ray crystallography.