379270-37-8 Usage
Description
Tenofovir Alafenamide, also known as GS-7340, is an L-alanine derivative and a prodrug of the reverse transcriptase inhibitor Tenofovir (T018500). It is used to treat HIV and Hepatitis B and was developed by Gilead Sciences. Compared to tenofovir disoproxil fumarate, tenofovir alafenamide has a greater antiviral activity and better distribution into lymphoid tissues. It is an oral phosphonoamidate prodrug that was approved by the USFDA for the treatment of chronic hepatitis B virus infection with compensated liver disease.
Uses
Used in Antiviral Applications:
Tenofovir Alafenamide is used as an antiviral agent for the treatment of HIV and Hepatitis B. It acts as a reverse transcriptase inhibitor, preventing the replication of the virus and reducing the viral load in the body.
Used in HIV Treatment:
Tenofovir Alafenamide is used as an antiretroviral medication in combination therapy for the treatment of HIV-1 infection. It helps in suppressing the viral replication and maintaining the health of patients living with HIV.
Used in Hepatitis B Treatment:
Tenofovir Alafenamide is used as an antiviral medication for the treatment of chronic hepatitis B virus infection with compensated liver disease. It helps in reducing the viral load and preventing the progression of liver disease.
Used in Drug Development:
Tenofovir Alafenamide serves as a potentially safer form of the previously approved tenofovir disoproxil fumarate (Viread), contributing to the development of more effective and safer antiviral medications for the treatment of HIV and Hepatitis B.
Synthesis
A multikilogram synthesis of tenofovir alafenamide fumarate
was described in a Gilead patent. Additional process
improvements on specific steps of the Gilead process have
been reported on 100 g scale, and these will be noted
throughout the description of the synthesis. The synthesis was
initiated with the alkylation of adenine (72) with (R)-propylene
carbonate (73) to give hydroxypropyl adenine 74 in 75% yield. It should be noted that sodium hydroxide can be
replaced by potassium bases with increased yields on 100 g
scale.27 Alkylation of 74 with diethyl p-toluenesulfonyloxymethylphosphonate
(75) gave intermediate 76, which was not
isolated. Hydrolysis of the phosphonate esters with trimethylsilyl
bromide followed by recrystallization from water gave
phosphonic acid 77 in 50% yield. Interestingly, replacing
Mg(Ot-Bu)2 with PhMgCl/t-BuOH led to improved yields for
the alkylation step (74 → 76) on a 100 g scale. Additionally,
the authors note that conditions for hydrolyzing the
phosphonate ester can be modified using HCl or HBr for
improved yields on smaller scale. Dicyclohexylcarbodiimide
(DCC) coupling of 77 with phenol produced phosphonate 78
in 51% yield. This step was also reported to proceed in higher
yield on smaller scale by changing the solvent to cyclopentylmethyl
ether. Monophosphonate ester 78 was treated
with thionyl chloride followed by L-alanine isopropyl ester (79)
and triethylamine to give tenofovir alafenamide rac-80 as a
mixture of phosphonate diastereomers in 47% yield. The
diastereomers were separated using simulated moving bed
chromatography to give the desired diastereomer ent-80 in
47% yield and 99% diastereomeric purity. The diastereomers
could also be separated using a crystallization-induced dynamic
resolution of rac-80. Tenofovir alafenamide fumarate (VI)
was prepared from ent-80 and fumaric acid in 83% yield.
Check Digit Verification of cas no
The CAS Registry Mumber 379270-37-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,7,9,2,7 and 0 respectively; the second part has 2 digits, 3 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 379270-37:
(8*3)+(7*7)+(6*9)+(5*2)+(4*7)+(3*0)+(2*3)+(1*7)=178
178 % 10 = 8
So 379270-37-8 is a valid CAS Registry Number.
379270-37-8Relevant articles and documents
Method for preparing antiviral drug tenofovir alafenamide fumarate
-
, (2022/04/09)
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.
Preparation method of tenofovir alafenamide
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Paragraph 0050; 0053; 0054; 0064-0067, (2020/05/01)
The invention relates to a preparation method of tenofovir alafenamide represented by a formula IV. The preparation method comprises the following steps: 1) performing a halogenation reaction on a compound I and a halogenation reagent to obtain a halogenated compound II, wherein the halogenated compound II is a raceme; 2) performing solvent-mediated asymmetric transformation on the halogenated compound II obtained in the step 1) in an organic solvent B, and removing the solvent after the complete reaction to obtain a compound III, wherein the asymmetric conversion reaction is carried out at atemperature lower than the reflux temperature of the organic solvent B, a ratio S/R of the two diastereoisomers in the compound III is greater than or equal to 90%, and the organic solvent B is one ora combination comprising one or a plurality of materials selected from toluene, dimethylbenzene, ethylbenzene and chlorobenzene; and (3) carrying out an amidation reaction on the compound III obtained in the step (2) and L-alanine isopropyl ester or a salt thereof to prepare the tenofovir alafenamide represented by the formula IV. The preparation method disclosed by the invention can be used forenhancing the reaction controllability and shortening the reaction time, and is suitable for industrial production of TAF.
Efficient synthesis technology of tenofovir alafenamide
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Paragraph 0040; 0049-0056, (2019/10/01)
The invention discloses an efficient synthesis technology of tenofovir alafenamide. The efficient synthesis technology comprises the steps that A, tenofovir reacts with triphenyl phosphite under an alkali catalysis condition to prepare tenofovir monophenyl ester, wherein the initial reaction temperature is 50-70 DEG C, the reaction temperature rises according to the gradient of 5-10 DEG C/h, and the total reaction duration is 6-10 h; B, the tenofovir monpohenyl ester is subjected to acylating chlorination to prepare tenofovir phenyl ester phosphoryl chloride; C, the tenofovir phenyl ester phosphoryl chloride is isomerized, then the isomerized tenofovir phenyl ester phosphoryl chloride reacts with an L-alanine isopropyl ester compound to prepare a target compound, wherein methylbenzene andother non-polar solvents are adopted for an isomerization solvent. The prepared tenofovir alafenamide has high purity and high yield, the technology operation is simple, the cost is low, complicated technology operation and purification means like using chiral resolution agents are omitted, and the efficient synthesis technology is very suitable for industrial production.
