202138-50-9

Basic information

• Product Name: Tenofovir disoproxil fumarate
• Synonyms: (((((1-(6-aMino-9H-purin-9-yl)propan-2-yl)oxy)Methyl)phosphoryl)bis(oxy))bis(Methylene) diisopropyl dicarbonate fuMarate;enofovir disoproxil fuMarate;Tenofovir Disproxil FuMarate;Tenofovir Disoproxil FuMarate I;FuMaric acid tenofovir ester;2,4,6,8-Tetraoxa-5-phosphanonanedioic acid, 5-[[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]-, 1,9-bis(1-methylethyl) ester, 5-oxide, (2E)-2-butenedioate (1:1);GS-1278 Disoproxil Fumarate;Tenofovir disoproxil fumarate 9-((R)-2-((Bis(((isopropoxycarbonyl)oxy)methoxy)phosphinyl)methoxy)propyl)adenine fumarate
• CAS NO: 202138-50-9
• Molecular Formula: C₄H₄O₄*C₁₉H₃₀N₅O₁₀P
• Molecular Weight: 635.51
• EINECS: 1308068-626-2
• Product Categories: Inhibitors;Tenofovir;Bases & Related Reagents;Intermediates & Fine Chemicals;Nucleotides;Pharmaceuticals;Phosphorylating and Phosphitylating Agents
• Mol File: 202138-50-9.mol
• Article Data: 42

Chemical Properties

• Melting Point: 113-115°C
• Boiling Point: 642.7 °C at 760 mmHg
• Flash Point: 342.5 °C
• Appearance: almost white crystalline
• Density: 1.45 g/cm³
• Vapor Pressure: 2.06E-16mmHg at 25°C
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Methanol (Slightly)
• CAS DataBase Reference: Tenofovir disoproxil fumarate(CAS DataBase Reference)
• NIST Chemistry Reference: Tenofovir disoproxil fumarate(202138-50-9)
• EPA Substance Registry System: Tenofovir disoproxil fumarate(202138-50-9)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• Hazardous Substances Data: 202138-50-9(Hazardous Substances Data)

Usage

Description

Tenofovir disoproxil fumarate (tenofovir DF) is a prodrug of the acyclic nucleoside phosphonate, tenofovir, developed by Gilead Sciences under the trade name "Viread." It is a nucleotide-analogues antiretroviral drug that acts as a reverse transcriptase inhibitor, blocking the enzyme crucial to viral production in HIV-infected individuals. It is also effective against hepatitis B virus polymerase. Tenofovir disoproxil fumarate is rapidly converted to tenofovir in vivo, which then undergoes two intracellular phosphorylation steps to form the active tenofovir diphosphate. Tenofovir disoproxil fumarate is a potent competitive inhibitor for reverse transcriptase and, once incorporated into DNA, causes DNA chain termination. It is unique in demonstrating efficacy against 3TC (lamivudine)-resistant HIV strains and has a long intracellular half-life, allowing for once-daily dosing.

Uses

Used in Pharmaceutical Industry:
Tenofovir disoproxil fumarate is used as a pharmaceutical secondary standard for quality control in pharma laboratories and manufacturing, providing a convenient and cost-effective alternative to in-house working standards.
Used in HIV Treatment:
Tenofovir disoproxil fumarate is used as an anti-HIV agent for the treatment of HIV infection. It is an acyclic phosphonate nucleotide analog and a selective HIV-1 reverse transcriptase inhibitor, which helps in reducing the level of HIV in the blood and is effective even in patients whose HIV has developed resistance to currently available antiretroviral drugs.
Used in Hepatitis B Treatment:
Tenofovir disoproxil fumarate is used as an antiviral agent for the treatment of chronic hepatitis B virus (HBV) infection in adults and children aged 12 years and older.
Used in Skin Care Industry:
Although not explicitly mentioned in the provided materials, tenofovir disoproxil fumarate has been studied for its potential use as a tyrosinase inhibitor, which could be utilized for skin lightening and anti-melasma applications in the skin care industry.

Indication and application

Tenofovir disoproxil fumarate[trade name: Viread?], an antiviral drug, is indicated as the treatment for both HIV and Hepatitis B virus[HBV]. Viread? is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 2 years of age and older. It is also indicated for the treatment of chronic hepatitis B in adults and pediatric patients 12 years of age and older[2,9].

Mode of action

Tenofovir[the prodrug type of Viread] can effectively inhibit the activity of HIV reverse transcriptase by competing with the natural substrate deoxyadenosine 5'-triphosphate and, after incorporation into DNA, leading to DNA chain termination[1, 5, 7, 8]. Specifically, the drugs are analogues of the naturally occurring deoxynucleotides needed to synthesize the viral DNA and they compete with the natural deoxynucleotides for incorporation into the growing viral DNA chain[8, 10, 11]. However, unlike the natural deoxynucleotides substrates, NRTIs and NTRTIs[nucleoside/tide reverse transcriptase inhibitors] lack a 3'-hydroxyl group on the deoxyribose moiety. As a result, following incorporation of an NRTI or an NtRTI, the next incoming deoxynucleotide cannot form the next 5'-3' phosphodiester bond needed to extend the DNA chain. Thus, when an NRTI or NtRTI is incorporated, viral DNA synthesis is halted, a process known as chain termination. All NRTIs and NtRTIs are classified as competitive substrate inhibitors[2].

Adverse reactions

Common adverse reactions include back pain, headache, lack or loss of strength, pain, redness of the skin, skin rash as well as itching skin[3]. Severe adverse reactions of Tenofovir disoproxil fumarate may include severe acute exacerbation of Hepatitis, new onset or worsening renal impairment, lactic acidosis/severe hepatomegaly with steatosis, bone effects and immune re-constitution syndrome and liver impairment[3]. Some less common side effects include chest pain, cough, fever of chills, weight loss, joint pain and swelling, itching and crawling tightness in the chest and trouble in breathing. In rare cases, abdominal or stomach discomfort, decreased appetite, diarrhea, fast, shallow breathing, general feeling of discomfort, muscle pain or cramping, unusual tiredness or weakness could occur[4, 9].

Warning and precaution

Viread should not be taken together with adefovir[Hepsera], or with used in combination with medicines that contain tenofovir[Atripla, Biktarvy, Cimduo, Complera, Descovy, Genvoya, Odefsey, Stribild, Symfi, or Truvada]. If patients have ever had chronic hepatitis B, Viread can restore the condition or even worse it. In this case, frequent blood tests is required to check your liver function. Do not stop using tenofovir disoproxil without first talking to your healthcare providers. This medicine may cause a serious condition called lactic acidosis[1, 3, 4, 9]. Get emergency medical help if you have even mild symptoms such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired. Viread can also cause severe or life-threatening effects on your liver. Call your doctor at once if you have: nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice[yellowing of the skin or eyes][3, 4, 9]. Children with HIV who are younger than 2 years old as well as children with hepatitis B who are younger than 12 years old should be disabled from using Viread[3, 9]. Patients who have liver diseases, kidney disease or with low bone mineral density should ask doctors for advice before taking Viread. It may be not that safe for Women during pregnant or lactation stage to take Viread, so consult doctors before using it[3]. Bone mineral density monitoring should be considered in patients who have a history of pathologic bone fracture or at risk for osteopenia[9]. Some more tips: Avoid sharing needles or other injection equipment as well as personal items that can have blood or body fluids on them, liketoothbrushes and razor blades. Avoid having any kind of sex without protection. Always practice safer sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood. Avoid breastfeed since tenofovir is excreted in breast milk and it is not known whether it can harm the baby. Mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in the breast milk[9]. Viread may cause either lactic acidosis or severe liver problem. Ask the doctor for help immediately when you have the following symptoms: feeling weak or tired, unusual muscle pain, trouble breathing, stomach pain associated with nausea or vomiting, feeling dizzy or lightheaded, fast or irregular heartbeat or cold or blue hands or feet, yellowing skin and whiting eye, dark-colored unit, loss of appetite, nausea and light-colored bowel movement[3,9].

References

Editor, Text. "New Antiretroviral for HIV Infection. approved by the FDA tenofovir disoproxil fumarate Viread." American Family Physician[2002]. https://www.drugbank.ca/drugs/DB00300 https://aidsinfo.nih.gov/drugs/290/tenofovir-disoproxil-fumarate/0/patient/ https://www.drugs.com/pro/viread.html Coleman, C., J. Ross, and P. Reddy. "Tenofovir disoproxil fumarate: The first nucleotide reverse transcriptase inhibitor for treatment of patients with HIV-1 infection." Formulary[2002]. Cooper, R. D, et al. "Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients. " Clinical Infectious Diseases 51.5(2010]:496-505. Lysengwilliamson, K. A., N. A. Reynolds, and G. L. Plosker. "Tenofovir disoproxil fumarate: a review of its use in the management of HIV infection. " Drugs 65.8(2005]:413-432. Heathcote, E. J., et al. "Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B. " Gastroenterology140.1(2011]:132-143. https://www.rxlist.com/viread-drug.htm#indications_dosage Miller MD, Margot NA, Hertogs K, Larder B, Miller V: Antiviral activity of tenofovir[PMPA] against nucleoside-resistant clinical HIV samples. Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7]:1025-8. Buti, M, and M. Homs. "Tenofovir disoproxil fumarate in the treatment of chronic hepatitis B." Expert Rev Gastroenterol Hepatol 6.4(2012]:413-421.

Originator

Gilead Sciences (US)

Biochem/physiol Actions

Tenofovir disoproxil fumarate is a prodrug of tenofovir, a nucleotide analogue reverse transcriptase inhibitor (nRTI) that causes premature termination of DNA transcription. In a T cell line and primary blood lymphocytes, the antiviral activity of tenofovir disoproxil was shown to be more than 100-fold greater than tenofovir because of its rapid intracellular uptake. Tenofovir disoproxil fumarate has been used alone and in various combinations for the prevention and treatment of HIV/AIDS and chronic hepatitis B infections and is on the World Health Organization′s List of Essential Medicines.

references

[1] fung hb, stone ea, piacenti fj. tenofovir disoproxil fumarate: a nucleotide reverse transcriptase inhibitor for the treatment of hiv infection. clin ther. 2002 oct;24(10):1515-48.[2] brian p. kearney, john f. flaherty, jaymin shah. tenofovir disoproxil fumarate. clinical pharmacokinetics. august 2004, volume 43, issue 9, pp 595-612

InChI:InChI=1/C19H30N5O10P.C4H4O4/c1-12(2)33-18(25)28-9-31-35(27,32-10-29-19(26)34-13(3)4)11-30-14(5)6-24-8-23-15-16(20)21-7-22-17(15)24;5-3(6)1-2-4(7)8/h7-8,12-14H,6,9-11H2,1-5H3,(H2,20,21,22);1-2H,(H,5,6)(H,7,8)/b;2-1+/t14-;/m1./s1

Synthetic route

(2E)-but-2-enedioic acid (110-17-8) + tenofovir disoproxil → tenofovir disoproxyl fumarate (202138-50-9)

Conditions	Yield
In isopropyl alcohol at 50 - 55℃;	94.4%
In isopropyl alcohol at 50 - 55℃; for 1h;	92.2%
In methanol; water at 0 - 75℃; for 0.5h; Solvent; Temperature;	90%

chloromethyl isopropyl carbonate (35180-01-9) + (2E)-but-2-enedioic acid (110-17-8) + tenofovir (147127-20-6) → tenofovir disoproxyl fumarate (202138-50-9)

Conditions	Yield
Stage #1: tenofovir With triethylamine In 1-methyl-pyrrolidin-2-one at 63℃; for 0.5h; Stage #2: chloromethyl isopropyl carbonate In 1-methyl-pyrrolidin-2-one at 63℃; for 4h; Stage #3: (2E)-but-2-enedioic acid In isopropyl alcohol at 50℃; for 0.5h; Concentration;	90%
Stage #1: chloromethyl isopropyl carbonate; tenofovir With tetrabutylammomium bromide; triethylamine at 50℃; for 3h; Inert atmosphere; Stage #2: (2E)-but-2-enedioic acid In isopropyl alcohol Reagent/catalyst; Temperature; Reflux;	78.8%
Stage #1: chloromethyl isopropyl carbonate; tenofovir With tetrabutylammomium bromide; triethylamine In 1-methyl-pyrrolidin-2-one; toluene at 45 - 55℃; for 5h; Stage #2: (2E)-but-2-enedioic acid In isopropyl alcohol at 50 - 55℃; for 2h;	63.6%

9-[2-[(R)[[bis[[isopropoxycarbonyl]oxy]methoxy]phosphinyl]methoxy]propyl]adenine orotate + (2E)-but-2-enedioic acid (110-17-8) → tenofovir disoproxyl fumarate (202138-50-9)

Conditions	Yield
Stage #1: 9-[2-[(R)[[bis[[isopropoxycarbonyl]oxy]methoxy]phosphinyl]methoxy]propyl]adenine orotate With triethylamine In dichloromethane; water at 25℃; Stage #2: (2E)-but-2-enedioic acid In isopropyl alcohol at 0 - 50℃;	83%

adenine (66224-66-6, 66224-67-7, 66224-68-8, 66224-69-9, 134434-48-3, 134434-49-4, 134454-76-5, 134461-75-9) → tenofovir disoproxyl fumarate (202138-50-9)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: sodium hydroxide / N,N-dimethyl-formamide / 120 °C 2.1: magnesium 2-methylpropan-2-olate / 1-methyl-pyrrolidin-2-one / 70 - 74 °C 3.1: chloro-trimethyl-silane; sodium bromide / 1-methyl-pyrrolidin-2-one / 0 - 75 °C 4.1: triethylamine / 1-methyl-pyrrolidin-2-one / 45 °C 4.2: 5.5 h / 45 - 50 °C 5.1: isopropyl alcohol / 2 h / 50 °C View Scheme
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 100 - 120 °C / Inert atmosphere 1.2: 8 h / 120 °C 2.1: magnesium 2-methylpropan-2-olate / N,N-dimethyl-formamide; water / 44 h / -15 - 20 °C / Inert atmosphere 3.1: hydrogenchloride / water / 0.5 h / 140 °C / Microwave irradiation 4.1: triethylamine / 1-methyl-pyrrolidin-2-one / 1 h / 45 °C / Inert atmosphere 4.2: 5 h / 60 °C 5.1: cyclohexane / 0.17 h / 60 °C View Scheme
Multi-step reaction with 5 steps 1.1: sodium carbonate / N,N-dimethyl-formamide / 6 h / 95 °C 2.1: lithium tert-butoxide / N,N-dimethyl-formamide / 2 h / 0 - 20 °C 2.2: 0 °C 3.1: hydrogen bromide / 8 h / 80 °C 4.1: triethylamine; benzyltriethylammonium bromide / N,N-dimethyl-formamide / 4 h / 60 °C 5.1: isopropyl alcohol / 2.5 h / 60 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydroxide / N,N-dimethyl-formamide / 0.33 h / 20 °C 1.2: 24.5 h / 120 °C 2.1: lithium tert-butoxide / N,N-dimethyl-formamide / 30 - 35 °C 3.1: trimethylsilyl bromide / acetonitrile / 5 h / Reflux 4.1: triethylamine; tetrabutylammomium bromide / 1-methyl-pyrrolidin-2-one; toluene / 5 h / 45 - 55 °C 4.2: 2 h / 50 - 55 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydroxide / N,N-dimethyl-formamide / 0.33 h / 20 °C 1.2: 24.5 h / 120 °C 2.1: magnesium 2-methylpropan-2-olate; calcium hydride / N,N-dimethyl-formamide / 30 - 35 °C 3.1: trimethylsilyl bromide / acetonitrile / 5 h / Reflux 4.1: toluene; 1-methyl-pyrrolidin-2-one / 60 °C 4.2: 5 h / 45 - 55 °C 4.3: 2 h / 50 - 55 °C View Scheme

(R)-9-(2-hydroxypropyl)adenine (14047-28-0) → tenofovir disoproxyl fumarate (202138-50-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: magnesium 2-methylpropan-2-olate / 1-methyl-pyrrolidin-2-one / 70 - 74 °C 2.1: chloro-trimethyl-silane; sodium bromide / 1-methyl-pyrrolidin-2-one / 0 - 75 °C 3.1: triethylamine / 1-methyl-pyrrolidin-2-one / 45 °C 3.2: 5.5 h / 45 - 50 °C 4.1: isopropyl alcohol / 2 h / 50 °C View Scheme
Multi-step reaction with 4 steps 1.1: magnesium 2-methylpropan-2-olate / toluene; 1-methyl-pyrrolidin-2-one / 6 h / 25 - 75 °C 1.2: 1 h 1.3: 90 - 95 °C 2.1: toluene / 20 - 110 °C 3.1: chloro-trimethyl-silane; triethylamine; tetrabutylammomium bromide / 1-Methylpyrrolidine / 50 - 55 °C 3.2: 5 h / 50 - 55 °C 4.1: isopropyl alcohol / 50 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 1 h / 0 - 35 °C 1.2: 2 h / 25 - 30 °C 1.3: 5 h / 25 - 75 °C 2.1: hydrogen bromide / water / 5 h / 90 - 95 °C 2.2: 4 h / 0 - 30 °C / pH 2.5 - 3 3.1: triethylamine / cyclohexane / 2 h / 80 - 85 °C 3.2: 4 h / 50 - 55 °C 4.1: isopropyl alcohol / 0.33 h / 50 - 55 °C 4.2: 5.5 h / 0 - 55 °C View Scheme

tenofovir (147127-20-6) → tenofovir disoproxyl fumarate (202138-50-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine / 1-methyl-pyrrolidin-2-one / 45 °C 1.2: 5.5 h / 45 - 50 °C 2.1: isopropyl alcohol / 2 h / 50 °C View Scheme
Multi-step reaction with 3 steps 1.1: toluene / 20 - 110 °C 2.1: chloro-trimethyl-silane; triethylamine; tetrabutylammomium bromide / 1-Methylpyrrolidine / 50 - 55 °C 2.2: 5 h / 50 - 55 °C 3.1: isopropyl alcohol / 50 °C View Scheme
Multi-step reaction with 2 steps 1.1: triethylamine / 1-methyl-pyrrolidin-2-one / 1 h / 45 °C / Inert atmosphere 1.2: 5 h / 60 °C 2.1: cyclohexane / 0.17 h / 60 °C View Scheme

(R)-diethyl (((1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate (180587-75-1) → tenofovir disoproxyl fumarate (202138-50-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: chloro-trimethyl-silane; sodium bromide / 1-methyl-pyrrolidin-2-one / 0 - 75 °C 2.1: triethylamine / 1-methyl-pyrrolidin-2-one / 45 °C 2.2: 5.5 h / 45 - 50 °C 3.1: isopropyl alcohol / 2 h / 50 °C View Scheme
Multi-step reaction with 3 steps 1.1: hydrogen bromide / water / 5 h / 90 - 95 °C 1.2: 4 h / 0 - 30 °C / pH 2.5 - 3 2.1: triethylamine / cyclohexane / 2 h / 80 - 85 °C 2.2: 4 h / 50 - 55 °C 3.1: isopropyl alcohol / 0.33 h / 50 - 55 °C 3.2: 5.5 h / 0 - 55 °C View Scheme
Multi-step reaction with 3 steps 1.1: hydrogen bromide / water / 2 h / 90 - 95 °C 1.2: 5 h / 0 - 30 °C / pH 2.5 2.1: triethylamine / cyclohexane / 2 h / 20 - 85 °C 2.2: 4 h / 25 - 55 °C 2.3: pH 6.5 - 7.5 3.1: isopropyl alcohol / 0.33 h / 50 - 55 °C 3.2: 5.5 h / 0 - 55 °C View Scheme

tenofovir disoproxil chloromethyl-isopropyl carbonate (1215085-38-3) + (2E)-but-2-enedioic acid (110-17-8) → tenofovir disoproxyl fumarate (202138-50-9)

Conditions	Yield
In isopropyl alcohol at 50℃;

chloromethyl isopropyl carbonate (35180-01-9) + (x)C6H15N*C9H14N5O4P → tenofovir disoproxyl fumarate (202138-50-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: chloro-trimethyl-silane; triethylamine; tetrabutylammomium bromide / 1-Methylpyrrolidine / 50 - 55 °C 1.2: 5 h / 50 - 55 °C 2.1: isopropyl alcohol / 50 °C View Scheme

bis(2-propyl) (R)-9-(2-phosphonomethoxypropyl)adenine (160616-04-6) → tenofovir disoproxyl fumarate (202138-50-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogenchloride / water / 0.5 h / 140 °C / Microwave irradiation 2.1: triethylamine / 1-methyl-pyrrolidin-2-one / 1 h / 45 °C / Inert atmosphere 2.2: 5 h / 60 °C 3.1: cyclohexane / 0.17 h / 60 °C View Scheme

tenofovir disoproxyl fumarate (202138-50-9) → ({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonic acid

Conditions	Yield
With phosphoric acid In water; isopropyl alcohol at 60℃; for 0.5h;	90%
With phosphoric acid In water; isopropyl alcohol at 60℃; for 0.5h;	90%

formaldehyd (50-00-0) + tenofovir disoproxyl fumarate (202138-50-9) → C59H90N15O30P3

Conditions	Yield
In N,N-dimethyl-formamide at 80℃; for 6h;	11.24%

formaldehyd (50-00-0) + tenofovir disoproxyl fumarate (202138-50-9) → C39H60N10O20P2

Conditions	Yield
In N,N-dimethyl-formamide at 80℃; for 1h;	8.1%

formaldehyd (50-00-0) + Tenofovir mono-POC + tenofovir disoproxyl fumarate (202138-50-9) → C34H52N10O17P2

Conditions	Yield
In N,N-dimethyl-formamide at 80℃; for 13h;	5.67%

tenofovir disoproxyl fumarate (202138-50-9) → 9-[(R)-2-[[bis[[ (isopropoxycarbonyl)oxy]methoxy]phosphinyl]-methoxy]propyl]adenine fumarate Tenofovir disoproxil fumarate

Conditions	Yield
In Methyl isobutyl carbinol at 22 - 60℃; for 48h; Product distribution / selectivity;
In tetrahydrofuran; 1-methyl-pyrrolidin-2-one at 5 - 60℃; under 150.015 Torr; Product distribution / selectivity;
In tetrahydrofuran; nitrobenzene at 5 - 60℃; under 150.015 Torr; Product distribution / selectivity;

tenofovir disoproxyl fumarate (202138-50-9) → tenofovir disoproxil

Conditions	Yield
With sodium hydrogencarbonate In water; ethyl acetate at 20℃; for 0.666667h; pH=7;	35 g
With sodium hydrogencarbonate In Isopropyl acetate; water at 22℃; for 0.5h; Reagent/catalyst;

25,26,27,28-terahydroxycalix[4]arene-5,11,7,23-tetrasulfonic acid (386768-13-4, 189397-70-4, 112269-92-8) + tenofovir disoproxyl fumarate (202138-50-9) → C19H30N5O10P*C28H24O16S4

Conditions	Yield
In dimethylsulfoxide-d6

tenofovir disoproxyl fumarate (202138-50-9) + para-sulphonato-thiacalix[4]arene → C19H30N5O10P*C24H16O16S8

Conditions	Yield
In dimethylsulfoxide-d6

Upstream product

• 110-17-8 (2E)-but-2-enedioic acid 
• 160616-04-6 bis(2-propyl) (R)-9-(2-phosphonomethoxypropyl)adenine 
• 35180-01-9 chloromethyl isopropyl carbonate 
• 147127-20-6 tenofovir 
• 1215085-38-3 tenofovir disoproxil chloromethyl-isopropyl carbonate 
• 180587-75-1 (R)-diethyl (((1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate 
• 14047-28-0 (R)-9-(2-hydroxypropyl)adenine 
• 66224-66-6 adenine 
• 201341-05-1 tenofovir disoproxil 

Downstream Products

• 1432630-26-6 9-[(R)-2-[[bis[[ (isopropoxycarbonyl)oxy]methoxy]phosphinyl]-methoxy]propyl]adenine fumarate Tenofovir disoproxil fumarate 
• 201341-05-1 tenofovir disoproxil 

Relevant articles and documents

METHODS FOR IMPROVING PURITY OF TENOFOVIR DISOPROXIL FUMARATE, AND COMPOSITIONS THEREOF

Methods for producing tenofovir disoproxil fumarate with improved purity are provided. In particular, methods for producing tenofovir disoproxil fumarate with reduced levels of chloromethyl isopropyl carbonate are described. Also described are compositions containing tenofovir disoproxil fumarate with improved purity, and an analysis method that can be used to determine the purity of such compositions with improved accuracy and sensitivity.

A method for preparing for [...] (by machine translation)

The invention relates to a method for preparing for [...]. Specifically, the invention relates to an industrial production level of preparation for fuwei two pyrrole fufu ester of the method, the method can improve the reaction yield, reducing the impurity, is simple and easy to control, is conducive to industrial expansion of production. (by machine translation)

Preparation method of tenofovir disoproxil fumarate

The invention provides a preparation method of tenofovir disoproxil fumarate. The preparation method comprises the following steps: performing an etherification reaction, performing a hydrolysis reaction, performing a condensation reaction, and performing refining and performing a salt forming reaction to obtain the tenofovir disoproxil fumarate. According to the method provided by the invention,the tenofovir disoproxil fumarate prepared by the method has a high yield, and is easy to purify and suitable for industrialized mass production.