1392275-56-7

Basic information

• Product Name: Tenofovir Alafenamide Fumarate
• 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;Anti-HIV;API-Anti-HBV
• CAS NO: 1392275-56-7
• Molecular Formula: C₄H₄O₄*C₂₁H₂₉N₆O₅P
• Molecular Weight: 592.55
• EINECS: -0
• Product Categories: API
• Mol File: 1392275-56-7.mol
• Article Data: 18

Chemical Properties

• Appearance: /
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• CAS DataBase Reference: Tenofovir Alafenamide Fumarate(CAS DataBase Reference)
• NIST Chemistry Reference: Tenofovir Alafenamide Fumarate(1392275-56-7)
• EPA Substance Registry System: Tenofovir Alafenamide Fumarate(1392275-56-7)

Safety Data

• Hazardous Substances Data: 1392275-56-7(Hazardous Substances Data)

Usage

Description

Tenofovir alafenamide hemifumarate is an investigational oral prodrug of Tenofovir. Tenofovir is a HIV-1 nucleotide reverse transcriptase inhibitor.

Chemical Properties

White to almost White crystal or crystalline powder.

Originator

Gilead Sciences

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.

Definition

ChEBI: A fumarate salt prepared from tenofovir alafenamide by reaction of one molecule of fumaric acid for every two molecules of tenofovir alafenamide. A prodrug for tenofovir, it is used in combination therapy for the treatment of HIV-1 infection.

Side effects

Check with your doctor immediately if any of the following side effects occur:Abdominal or stomach discomfort,bloody urine,dark urine,decreased appetite,decreased frequency or amount of urine,troubled breathing,cough,headache,back pain.

Synthesis

Under a nitrogen atmosphere, 200 g of isopropanol, 9 g of fumaric acid, and 50 g of TAF-3 were sequentially added to a 2 L reaction flask. Turn on the stirring, control the temperature at 40 ~ 50 °C, stir and dissolve, filter while hot, collect the mother liquor. Transfer the mother liquor to a 2L reaction bottle, start stirring, control the temperature at 40 ~ 50 °C, stir and dissolve, slowly reduce the temperature to 0 ~ 5 ° C, cooling time 2 ~ 3 hours, heat stirring for 10 hours. Filtration, drying at 60-65 ° C for 12 to 16 hours, to obtain 37.5 g of Tenofovir Alafenamide Fumarate finished product, white powder, yield 75.0%.

Upstream product

• 147127-20-6 tenofovir 
• 379270-35-6 ((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester 
• 101-02-0 triphenyl phosphite 
• 2053424-88-5 (((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)-D-alanine isopropyl ester 
• 39613-92-8 alanine isopropyl ester hydrochloride 
• 383365-04-6 N-[(R)-[[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]phenoxyphosphonyl]-L-alanine-1-methylethyl ester 
• 110-17-8 (2E)-but-2-enedioic acid 
• 379270-37-8 (S)-isopropyl-2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate 
• 108-95-2 phenol 
• 39825-33-7 isopropyl L-alanine 
• 66224-66-6 adenine 

Downstream Products

• 379270-37-8 (S)-isopropyl-2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate 

Relevant articles and documents

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.

Method for preparing antiviral drug tenofovir alafenamide fumarate

The invention discloses a method for preparing an antiviral drug tenofovir alafenamide fumarate, which comprises the following steps of: (1) reacting adenine with (R)-propylene carbonate to generate a compound I; (2) treating the compound I with magnesium tert-butoxide, and then adding phosphonate S to react to obtain a compound II; (3) the compound III is obtained by hydrolyzing the compound II in hydrobromic acid; (4) reacting the compound III with thionyl chloride to obtain phosphonyl chloride, and directly reacting the phosphonyl chloride with L-alanine isopropyl ester without purification to generate a compound IV; and (5) obtaining a final product, wherein the preparation of the propionyl phenol fumarate tenofovir is completed by salifying the compound IV and fumaric acid. The method has the advantages of few synthetic route steps, mild reaction conditions and principle saving, and can improve the yield of the final product.

CRYSTAL FORM OF TENOFOVIR ALAFENAMIDE SALT, PREPARATION METHOD AND USE THEREOF

Disclosed are a new polymorph II, crystal form A and B of 9-[(R)-2-[[(S)-[[(S)-1-(isopropoxycarbonyl)ethyl]amino]phenoxyphosphinyl]methoxy]propyl]adenine fumarate, and preparation methods and pharmaceutical use thereof. The crystal form II is a hemi-fumarate; the crystal form A is a mono-fumarate; and the crystal form B is a sesqui-fumarate. Compared with the existing crystal form, the new crystal forms have obvious advantages in solubility, stability and preparation process.