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147127-20-6

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147127-20-6 Usage

Uses

Different sources of media describe the Uses of 147127-20-6 differently. You can refer to the following data:
1. Tenofovir is an acyclic phosphonate nucleotide analogue and reverse transcriptase inhibitor. It is used as an anti-HIV agent. Antiviral.
2. Tenofovir is a drug used for the treatment of chronic heptatitis B as well as prevention and treatment of HIV/AIDS. It is a kind of nucleotide analog, acting as the reverse-transcriptase inhibitor (NtRTI). It inhibits the activity of HIV reverse transcriptase through competing with the natural substrate deoxyadenosine 5’-triphosphate, causing the termination of DNA chain.

Indications and Usage

Tenofovir disoproxil (Viread) is the first nucleotide analogue approved by the American FDA to treat HIV-1 infections. Tenofovir disoproxil is a drug used in the AIDS cocktail treatment method, and research shows that it has the ability to increase monkeys’ immunity to immunodeficiency viruses (similar to the human AIDS virus). Tenofovir disoproxil is used in combination with other reverse transcriptase inhibitors to treat HIV-1 infections and hepatitis B.

Mechanisms of Action

Tenofovir disoproxil is an acyclic nucleoside antivirus drug and has an inhibiting effect on HBV multi-enzyme complexes and HIV reverse transcriptase. Its active content tenofovir phosphonate directly competitively binds to natural deoxyribose substrate to inhibit the virus multi-enzyme complex and inserts itself into the DNA to end the nucleotide chain. Tenofovir disoproxil is barely absorbed by the gastrointestinal duct, so it undergoes esterification and ionization to become tenofovir ester fumarate. Tenofovir is soluble in water and can be quickly absorbed and decomposed into the active substance tenofovir, which then transforms into the active metabolite tenofovir phosphonate. As this drug is not metabolized by the CYP450 enzyme system, it has a very low chance of drug interactions caused by this enzyme.

Pharmacokinetics

Different sources of media describe the Pharmacokinetics of 147127-20-6 differently. You can refer to the following data:
1. Tenofovir disoproxil reaches peak blood concentration 1-2 hours after intake. Tenofovir disoproxil’s bioavailability increases by about 40% when taken with food. The intracellular half-life of tenofovir phosphonate is about 10 hours, so doses can be taken once daily. This drug is mainly filtered through renal glomeruli and excreted through the renal tubule transport system, with 70-80% excreted in its original form through urine.
2. Oral absorption: c. 25% Cmax 300 mg once daily: 0.3 mg/L Plasma half-life: 17 h Volume of distribution: 1.3 ± 0.6 L/kg at 3.0 mg/kg intravenous dose Plasma protein binding: <0.7% (in vitro) Absorption and distribution Oral bioavailability is poor, but is enhanced by administration as the disoproxil prodrug. It may be taken with or without food. CSF penetration is likely to be minimal due to the anionic charge of the molecule at physiological pH. It accumulates in semen at higher concentrations than in plasma. It is not known if it is distributed into breast milk. Metabolism and excretion Tenofovir is not metabolized and is principally eliminated by the kidneys by a combination of glomerular filtration and active tubular secretion. In patients with renal dysfunction the dose should be adjusted accordingly. Compounds such as cidofovir, aciclovir (acyclovir), valaciclovir, ganciclovir, valganciclovir and probenecid may compete for renal excretion. Tenofovir levels are increased when prescribed with some HIV protease inhibitors. The co-administration of tenofovir with didanosine leads to didanosine accumulation which is thought to occur through inhibition of purine nucleoside phosphorylase. This has been associated with impaired immune recovery and several cases of lactic acidosis and pancreatitis. If tenofovir is combined with didanosine the dose of didanosine should be reduced to 200 mg (<60 kg) or 250 mg (≥60 kg) per day and the patient monitored for symptoms of didanosine toxicity.

Adverse Effects

Weakness and exhaustion. Mild to moderate gastrointestinal reactions, including diarrhea, stomach pain, nausea, vomiting, bloating, lactic acid poisoning, hepatomegaly and fatty liver, and pancreatitis. These adverse reactions also commonly appear individually or combined when taking nucleoside analogues. Metabolic system hypophosphatemia (1% occurrence rate). Fat accumulation and redistribution, including centripetal obesity, buffalo hump, thin limbs, breast growth, and Cushing syndrome. May cause lactic acid poisoning, hepatomegaly related to steatosis, etc. Effects on nervous system: dizziness and headache. Effects on respiratory system: difficulty breathing. Effects on skin: drug rash.

Description

Tenofovir is an analog of adenosine monophosphate that has antiviral activity. It is converted by cellular enzymes to tenofovir diphosphate, an obligate chain terminator that inhibits the activity of HIV reverse transcriptase and hepatitis B virus polymerase. Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases α and β and mitochondrial DNA polymerase γ. For in vivo and cell culture use, tenofovir is supplied as a water soluble prodrug in the form of tenofovir disoproxil (fumarate) , which increases the intracellular diphosphorylated compound >1,000-fold above the level attained with unmodified tenofovir.

Chemical Properties

White Crystalline Solid

Indications

Tenofovir disoproxil fumarate (Viread) is a prodrug of tenofovir, a phosphorylated adenosine nucleoside analogue, and is the only available agent of its class. It is converted by cellular enzymes to tenofovir diphosphate, which competes with deoxyadenosine triphosphate (dATP) for access to reverse transcriptase and causes chain termination following its incorporation. Tenofovir was approved as part of a combination therapy for HIV in adults who failed treatment with other regimens; it appears to be effective against HIV strains that are resistant to NRTIs.

Definition

ChEBI: A member of the class of phosphonic acids that is methylphosphonic acid in which one of the methyl hydrogens is replaced by a [(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy group. An inhibitor of HIV-1 reverse transcriptase, the bis(isopropyloxycarbonyloxy ethyl) ester (disoproxil ester) prodrug is used as the fumaric acid salt in combination therapy for the treatment of HIV infection.

Acquired resistance

HIV variants with the K65R mutation and the K70E mutation in the reverse transcriptase demonstrate reduced susceptibility to tenofovir.

Pharmaceutical Applications

Different sources of media describe the Pharmaceutical Applications of 147127-20-6 differently. You can refer to the following data:
1. A nucleotide analog structurally similar to adefovir. EC50 values for HBV, assessed in the HepG2 2.2.15 cell line, ranged from 0.14 to 1.5 μm; the cytotoxic concentration exceeded 100 μm. A decline in HBV DNA levels below 105 copies/mL at 48 weeks of therapy in 100% of patients receiving tenofovir compared with 44% on adefovir therapy has been reported. There are also case reports of patients with primary resistance to adefovir responding to tenofovir. It is generally well tolerated in patients with chronic HBV; the most common side effects include nausea and gastrointestinal upset, headache, dizziness, fatigue and rash.
2. An acyclic nucleoside phosphonate, formulated as the disoproxil fumarate salt for oral administration.

Biological Activity

Selectively inhibits HIV reverse transcriptase (RNA-dependent DNA polymerase). Prevents cytotoxicity in SIV-infected C-8166 cells in vitro (IC 50 = 1.5 μ M). Antiviral agent.

Biochem/physiol Actions

Tenofovir has a low oral bioavailability. Hence, it is available as a prodrug called tenofovir disoproxil fumarate. Once ingested, tenofovir disoproxil fumarate is hydrolyzed to tenofovir and phosphorylated. This is then incorporated into the viral DNA which leads to chain termination. Tenofovir is also effective against hepatitis B virus.

Clinical Use

Chronic hepatitis B infection

Side effects

Different sources of media describe the Side effects of 147127-20-6 differently. You can refer to the following data:
1. In clinical trials of antiretroviral treatment-naive participants, the most commonly reported adverse events were mild to moderate gastrointestinal upset (nausea 8%, diarrhea 11%), headache (14%) and depression (11%). Tenofovir has the potential to result in nephrotoxicity, particularly through proximal tubular damage, but the risk of clinically significant renal dysfunction appears relatively low and seems to occur mainly in subjects with other identifiable risks for renal impairment. Minor elevations in serum creatinine and reductions in creatinine clearance occur, but rarely require drug discontinuation. A few (<0.1%) cases of osteomalacia and decreased bone density have been reported.
2. Tenofovir is taken once daily and is generally well tolerated, perhaps because it produces less mitochondrial toxicity than the NRTIs. Nausea, vomiting, flatulence, and diarrhea occur in 10% or fewer patients. Resistance to tenofovir has been documented, and cross-resistance to NRTIs may occur.

Check Digit Verification of cas no

The CAS Registry Mumber 147127-20-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,4,7,1,2 and 7 respectively; the second part has 2 digits, 2 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 147127-20:
(8*1)+(7*4)+(6*7)+(5*1)+(4*2)+(3*7)+(2*2)+(1*0)=116
116 % 10 = 6
So 147127-20-6 is a valid CAS Registry Number.
InChI:InChI=1/C9H14N5O4P/c1-6(18-5-19(15,16)17)2-14-4-13-7-8(10)11-3-12-9(7)14/h3-4,6H,2,5H2,1H3,(H2,10,11,12)(H2,15,16,17)/t6-/m0/s1

147127-20-6 Well-known Company Product Price

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  • TCI America

  • (T3006)  Tenofovir Hydrate  >98.0%(HPLC)(T)

  • 147127-20-6

  • 1g

  • 430.00CNY

  • Detail
  • TCI America

  • (T3006)  Tenofovir Hydrate  >98.0%(HPLC)(T)

  • 147127-20-6

  • 5g

  • 1,480.00CNY

  • Detail

147127-20-6SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 19, 2017

Revision Date: Aug 19, 2017

1.Identification

1.1 GHS Product identifier

Product name tenofovir (anhydrous)

1.2 Other means of identification

Product number -
Other names (R)-(1-(6-amino-9H-purin-9-yl)propan-2-yloxy)methylphosphonic acid

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:147127-20-6 SDS

147127-20-6Synthetic route

(R)-diethyl (((1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate
180587-75-1

(R)-diethyl (((1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
With hydrogenchloride In N,N-dimethyl-formamide at 130℃; under 7500.75 Torr; for 0.0416667h; Solvent; Pressure; Temperature; Inert atmosphere;95%
With trimethylsilyl bromide In acetonitrile at 65℃; for 1h;90%
With sulfuric acid at 90 - 110℃;83.8%
Conditions
ConditionsYield
With sodium hydroxide In water for 5h; Reflux;91.8%
bis(2-propyl) (R)-9-(2-phosphonomethoxypropyl)adenine
160616-04-6

bis(2-propyl) (R)-9-(2-phosphonomethoxypropyl)adenine

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
With hydrogenchloride In water at 130 - 140℃; Microwave irradiation; Sealed tube;91%
With hydrogenchloride In water at 140℃; for 0.5h; Temperature; Time; Reagent/catalyst; Microwave irradiation;90%
With hydrogenchloride In water at 140℃; for 0.5h; Temperature; Reagent/catalyst; Microwave irradiation;90%
Conditions
ConditionsYield
With potassium hydroxide In water for 5h; Reflux;88.7%
tenofovir disoproxil

tenofovir disoproxil

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
In ethyl acetate at 0 - 10℃; for 2h; Cooling with ice;85.4%
(R)-diethyl (((1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate
180587-75-1

(R)-diethyl (((1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate

A

magnesium para-toluenesulfonate

magnesium para-toluenesulfonate

B

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
With hydrogen bromide at 100℃; for 15h;A n/a
B 84.6%
Conditions
ConditionsYield
With sodium hydroxide In water for 5h; Reflux;82.5%
{[(4-methylbenzenesulfonyl)oxy]methyl}phosphonic acid
161760-09-4

{[(4-methylbenzenesulfonyl)oxy]methyl}phosphonic acid

(R)-9-(2-hydroxypropyl)adenine
14047-28-0

(R)-9-(2-hydroxypropyl)adenine

A

C9H14N5O4P

C9H14N5O4P

B

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
In 1-methyl-pyrrolidin-2-one at 0 - 20℃; Solvent; Reagent/catalyst; Temperature; Inert atmosphere; Molecular sieve;A 12%
B 82%
C12H18N5O5P

C12H18N5O5P

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
Stage #1: C12H18N5O5P With sodium hydroxide In water for 2h; Cooling with ice;
Stage #2: With hydrogenchloride; sodium hydroxide In water at 5℃; for 10h; pH=2.5;
81.3%
C13H20N5O5P

C13H20N5O5P

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
With hydrogenchloride In water at 90 - 110℃;78.1%
1-ethyl hydrogen ((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate

1-ethyl hydrogen ((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
With hydrogenchloride In water at 90 - 110℃;76.8%
C13H20N5O5P

C13H20N5O5P

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
With hydrogenchloride In water at 90 - 110℃;76.5%
Conditions
ConditionsYield
With sodium hydroxide In water for 5h; Reflux;76.2%
C11H18N5O4P

C11H18N5O4P

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
With hydrogenchloride In water at 90 - 110℃;75.7%
C15H24N5O5P

C15H24N5O5P

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
With hydrogenchloride In water at 90 - 110℃;74%
Stage #1: C15H24N5O5P With lithium hydroxide for 2h; Cooling with ice;
Stage #2: With hydrogenchloride; sodium hydroxide In water at 5℃; for 10h; pH=2.5;
74.5%
(di-tert-butoxyphosphoryl)methyl methanesulfonate

(di-tert-butoxyphosphoryl)methyl methanesulfonate

(R)-9-(2-hydroxypropyl)adenine
14047-28-0

(R)-9-(2-hydroxypropyl)adenine

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
Stage #1: (R)-9-(2-hydroxypropyl)adenine With magnesium 2-methylpropan-2-olate In N,N-dimethyl acetamide at 90℃; for 0.5h; Schlenk technique; Inert atmosphere;
Stage #2: (di-tert-butoxyphosphoryl)methyl methanesulfonate In N,N-dimethyl acetamide at 90℃; for 23h; Schlenk technique; Inert atmosphere;
Stage #3: With sulfuric acid at 60℃; Reagent/catalyst; Schlenk technique; Inert atmosphere;
72%
{[(4-methylbenzenesulfonyl)oxy]methyl}phosphonic acid
161760-09-4

{[(4-methylbenzenesulfonyl)oxy]methyl}phosphonic acid

(R)-9-(2-hydroxypropyl)adenine
14047-28-0

(R)-9-(2-hydroxypropyl)adenine

A

C10H17N5O7P2

C10H17N5O7P2

B

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
With magnesium chloride In 1-methyl-pyrrolidin-2-one at -20 - 20℃; Inert atmosphere;A 6%
B 69%
(di-tert-butoxyphosphoryl)methyl 4-methylbenzenesulfonate

(di-tert-butoxyphosphoryl)methyl 4-methylbenzenesulfonate

(R)-9-(2-hydroxypropyl)adenine
14047-28-0

(R)-9-(2-hydroxypropyl)adenine

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
Stage #1: (R)-9-(2-hydroxypropyl)adenine With magnesium 2-methylpropan-2-olate In N,N-dimethyl-formamide at 80℃; Schlenk technique; Inert atmosphere;
Stage #2: (di-tert-butoxyphosphoryl)methyl 4-methylbenzenesulfonate In N,N-dimethyl-formamide at 80℃; for 23h; Schlenk technique; Inert atmosphere;
Stage #3: With sulfuric acid at 60℃; Schlenk technique; Inert atmosphere;
68%
{[(4-methylbenzenesulfonyl)oxy]methyl}phosphonic acid
161760-09-4

{[(4-methylbenzenesulfonyl)oxy]methyl}phosphonic acid

(R)-9-(2-hydroxypropyl)adenine
14047-28-0

(R)-9-(2-hydroxypropyl)adenine

A

C10H17N5O7P2

C10H17N5O7P2

B

C9H14N5O4P

C9H14N5O4P

C

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
In N,N-dimethyl-formamide at 20℃; Reagent/catalyst; Solvent; Temperature; Inert atmosphere;A 8%
B 11%
C 64%
diethyl (p-toluenesulfonyloxymethane)phosphonate
31618-90-3

diethyl (p-toluenesulfonyloxymethane)phosphonate

(R)-9-(2-hydroxypropyl)adenine
14047-28-0

(R)-9-(2-hydroxypropyl)adenine

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
With bis(isopropoxy) magnesium In N,N-dimethyl-formamide at 45 - 65℃; for 11h; Autoclave; Inert atmosphere; Large scale;59.2%
Stage #1: diethyl (p-toluenesulfonyloxymethane)phosphonate; (R)-9-(2-hydroxypropyl)adenine With magnesium 2-methylpropan-2-olate In 1-methyl-pyrrolidin-2-one; toluene at 25 - 75℃; for 6h;
Stage #2: With water; acetic acid In 1-methyl-pyrrolidin-2-one; water; acetic acid; toluene for 1h;
Stage #3: With hydrogen bromide In 1-methyl-pyrrolidin-2-one; water; toluene at 90 - 95℃;
Stage #1: (R)-9-(2-hydroxypropyl)adenine With magnesium 2-methylpropan-2-olate In N,N-dimethyl-formamide at 20 - 35℃; for 0.5h;
Stage #2: diethyl (p-toluenesulfonyloxymethane)phosphonate In N,N-dimethyl-formamide at 75 - 80℃; for 2h;
Stage #3: With hydrogenchloride In N,N-dimethyl-formamide at 0 - 95℃; for 9h; Temperature; Reagent/catalyst;
82 g
With trimethylsilyl bromide; water; sodium hydroxide In dichloromethane at 0 - 5℃; for 3h; pH=2.5 - 3;
Stage #1: diethyl (p-toluenesulfonyloxymethane)phosphonate; (R)-9-(2-hydroxypropyl)adenine With alumina-supported potassium hydroxide In N,N-dimethyl-formamide at 40 - 130℃; for 18h;
Stage #2: With water at 100 - 105℃; for 18h; Reagent/catalyst; Temperature; Solvent;
(R)-(((1-chloropropan-2-yl)oxy)methyl)phosphonic acid bis(diethylamide)

(R)-(((1-chloropropan-2-yl)oxy)methyl)phosphonic acid bis(diethylamide)

7H-purin-6-ylamine
73-24-5

7H-purin-6-ylamine

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
Stage #1: (R)-(((1-chloropropan-2-yl)oxy)methyl)phosphonic acid bis(diethylamide); 7H-purin-6-ylamine With potassium phosphate In N,N-dimethyl acetamide at 120℃; for 24h; Inert atmosphere;
Stage #2: With hydrogenchloride In water at 80℃; for 0.75h; Inert atmosphere;
41%
(R)-diethyl (((1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate
180587-75-1

(R)-diethyl (((1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate

A

tenofovir
147127-20-6

tenofovir

B

(R)-9-(2-phosphonomethoxypropyl)hypoxanthine

(R)-9-(2-phosphonomethoxypropyl)hypoxanthine

Conditions
ConditionsYield
With hydrogenchloride
C15H30N5O4PSi2

C15H30N5O4PSi2

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
With water30.3 g
With water In acetonitrile
Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: NaOH / dimethylformamide / 20 h / 140 °C
2: LiOt-Bu / dimethylformamide; tetrahydrofuran / 1 h / 30 - 35 °C
3: 1.) bromotrimethylsilane, 2.) NaOH / 1.) acetonitrile, reflux, 2.) H2O, pH 3
View Scheme
Multi-step reaction with 3 steps
1: sodium hydroxide / N,N-dimethyl-formamide / 120 °C
2: magnesium 2-methylpropan-2-olate / 1-methyl-pyrrolidin-2-one / 70 - 74 °C
3: chloro-trimethyl-silane; sodium bromide / 1-methyl-pyrrolidin-2-one / 0 - 75 °C
View Scheme
Multi-step reaction with 3 steps
1.1: potassium hydroxide / N,N-dimethyl-formamide / 0.17 h / 25 - 30 °C
1.2: 25 - 120 °C
1.3: 0.17 h / 55 - 70 °C
2.1: magnesium 2-methylpropan-2-olate / dimethyl sulfoxide / 70 °C
3.1: sodium bromide; chloro-trimethyl-silane / 1-methyl-pyrrolidin-2-one / 16 h / 0 - 75 °C
View Scheme
(R)-9-(2-hydroxypropyl)adenine
14047-28-0

(R)-9-(2-hydroxypropyl)adenine

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: LiOt-Bu / dimethylformamide; tetrahydrofuran / 1 h / 30 - 35 °C
2: 1.) bromotrimethylsilane, 2.) NaOH / 1.) acetonitrile, reflux, 2.) H2O, pH 3
View Scheme
Multi-step reaction with 2 steps
1: 44 percent / NaH / dimethylformamide / 0 - 20 °C
2: 1.) TMSBr, 2.) H2O / 1.) MeCN, RT, 2.) acetone, 4 deg C
View Scheme
Multi-step reaction with 4 steps
1: 1.) chlorotrimethylsilane / 1) pyridine, room temperature, 1 h; 2) pyridine, room temperature, 2 h
2: sodium hydride / dimethylformamide / 48 h / Ambient temperature
3: sodium methoxide / dimethylformamide / Ambient temperature
4: 47 percent / bromotrimethylsilane / acetonitrile / Ambient temperature
View Scheme
(R)-1-(5-Amino-6-chloro-pyrimidin-4-ylamino)-propan-2-ol
17435-30-2

(R)-1-(5-Amino-6-chloro-pyrimidin-4-ylamino)-propan-2-ol

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: 86 percent / conc. HCl / Ambient temperature
2: 91 percent / NH3 / 65 °C
3: 44 percent / NaH / dimethylformamide / 0 - 20 °C
4: 1.) TMSBr, 2.) H2O / 1.) MeCN, RT, 2.) acetone, 4 deg C
View Scheme
(R)-1-(6-chloro-9H-purin-9-yl) propan-2-ol
180587-74-0

(R)-1-(6-chloro-9H-purin-9-yl) propan-2-ol

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: 91 percent / NH3 / 65 °C
2: 44 percent / NaH / dimethylformamide / 0 - 20 °C
3: 1.) TMSBr, 2.) H2O / 1.) MeCN, RT, 2.) acetone, 4 deg C
View Scheme
Multi-step reaction with 2 steps
1: ammonium hydroxide / 1,4-dioxane / 100 - 110 °C / Sealed tube; Large scale
2: bis(isopropoxy) magnesium / N,N-dimethyl-formamide / 11 h / 45 - 65 °C / Autoclave; Inert atmosphere; Large scale
View Scheme
(R)-9-<2-(2-tetrahydropyranyloxy)propyl>adenine
160616-02-4

(R)-9-<2-(2-tetrahydropyranyloxy)propyl>adenine

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: 85 percent / sulfuric acid / Ambient temperature
2: 1.) chlorotrimethylsilane / 1) pyridine, room temperature, 1 h; 2) pyridine, room temperature, 2 h
3: sodium hydride / dimethylformamide / 48 h / Ambient temperature
4: sodium methoxide / dimethylformamide / Ambient temperature
5: 47 percent / bromotrimethylsilane / acetonitrile / Ambient temperature
View Scheme
(R)-9-(2-hydroxypropyl)-N6-benzoyladenine
160616-03-5

(R)-9-(2-hydroxypropyl)-N6-benzoyladenine

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: sodium hydride / dimethylformamide / 48 h / Ambient temperature
2: sodium methoxide / dimethylformamide / Ambient temperature
3: 47 percent / bromotrimethylsilane / acetonitrile / Ambient temperature
View Scheme
[(R)-2-(6-Benzoylamino-purin-9-yl)-1-methyl-ethoxymethyl]-phosphonic acid diisopropyl ester
627510-49-0

[(R)-2-(6-Benzoylamino-purin-9-yl)-1-methyl-ethoxymethyl]-phosphonic acid diisopropyl ester

tenofovir
147127-20-6

tenofovir

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: sodium methoxide / dimethylformamide / Ambient temperature
2: 47 percent / bromotrimethylsilane / acetonitrile / Ambient temperature
View Scheme
N,N-dimethyl-formamide
68-12-2, 33513-42-7

N,N-dimethyl-formamide

tenofovir
147127-20-6

tenofovir

C12H17Cl2N6O2P

C12H17Cl2N6O2P

Conditions
ConditionsYield
With oxalyl dichloride In dichloromethane at 20℃; for 3h; Inert atmosphere;100%
With oxalyl dichloride In dichloromethane at 20℃; for 3h; Inert atmosphere;100%
tenofovir
147127-20-6

tenofovir

C9H13N5O4P(1-)*K(1+)

C9H13N5O4P(1-)*K(1+)

Conditions
ConditionsYield
With potassium hydrogencarbonate In water at 40℃;99.5%
triphenyl phosphite
101-02-0

triphenyl phosphite

tenofovir
147127-20-6

tenofovir

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester
379270-35-6

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester

Conditions
ConditionsYield
With pyridine at 50 - 115℃; for 6h;98%
With dmap; triethylamine at 100 - 110℃; Reagent/catalyst; Temperature;91%
With dmap; triethylamine In N,N-dimethyl acetamide at 105 - 110℃; for 20h; Reagent/catalyst; Temperature;89.03%
tenofovir
147127-20-6

tenofovir

C9H13N5O4P(1-)*Cs(1+)

C9H13N5O4P(1-)*Cs(1+)

Conditions
ConditionsYield
With caesium carbonate In water; acetone at 30℃;97.6%
tenofovir
147127-20-6

tenofovir

C9H13N5O4P(1-)*Li(1+)

C9H13N5O4P(1-)*Li(1+)

Conditions
ConditionsYield
With lithium hydroxide In acetone at 30℃;96.5%
diphenyl hydrogen phosphite
4712-55-4

diphenyl hydrogen phosphite

tenofovir
147127-20-6

tenofovir

phenol
108-95-2

phenol

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester
379270-35-6

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester

Conditions
ConditionsYield
With pyridine at 100 - 110℃; for 2h;95%
tenofovir
147127-20-6

tenofovir

phenol
108-95-2

phenol

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester
379270-35-6

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester

Conditions
ConditionsYield
With pyridine; dicyclohexyl-carbodiimide at 70℃; for 4h;93.63%
Stage #1: tenofovir; phenol In acetic acid butyl ester at 20℃; for 1h;
Stage #2: With dmap; triethylamine; dicyclohexyl-carbodiimide In acetic acid butyl ester at 90℃; for 24h;
85%
With triphenyl phosphite; dmap; triethylamine In toluene; acetonitrile at 100℃; for 28h; Solvent; Temperature;83%
tenofovir
147127-20-6

tenofovir

C18H26N10O7P2

C18H26N10O7P2

Conditions
ConditionsYield
With pyridine; dmap; phosphoric acid triphenyl ester In toluene; acetonitrile for 24h; Solvent; Temperature; Reagent/catalyst; Reflux;92.9%
With pyridine; triethylamine; dicyclohexyl-carbodiimide at 70℃; for 3h; Temperature; Reagent/catalyst;88.7%
With triethylamine; diisopropyl-carbodiimide In N,N-dimethyl-formamide at 90 - 100℃; for 22h; Solvent; Reagent/catalyst; Temperature;45.5%
phosphoric acid triphenyl ester
115-86-6

phosphoric acid triphenyl ester

tenofovir
147127-20-6

tenofovir

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester
379270-35-6

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester

Conditions
ConditionsYield
With dmap; triethylamine In 5,5-dimethyl-1,3-cyclohexadiene at 100 - 110℃; for 12h; Temperature; Solvent;91.97%
diphenyl hydrogen phosphite
4712-55-4

diphenyl hydrogen phosphite

tenofovir
147127-20-6

tenofovir

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester
379270-35-6

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester

Conditions
ConditionsYield
With pyridine at 110 - 120℃; for 4h;91.7%
chloromethyl isopropyl carbonate
35180-01-9

chloromethyl isopropyl carbonate

tenofovir
147127-20-6

tenofovir

tenofovir disoproxil

tenofovir disoproxil

Conditions
ConditionsYield
With tetrabutylammomium bromide; triethylamine In 1-methyl-pyrrolidin-2-one at 50℃; Temperature;91.5%
With triethylamine; N-butylpyridinium tetrafluoroborate at 40℃; for 1.5h; Reagent/catalyst; Temperature;90.6%
Stage #1: tenofovir With tetrabutylammomium bromide; triethylamine In 1-methyl-pyrrolidin-2-one at 50℃; for 0.5h;
Stage #2: chloromethyl isopropyl carbonate In 1-methyl-pyrrolidin-2-one at 60℃; for 4h; Reagent/catalyst; Solvent;
87.6%
tenofovir
147127-20-6

tenofovir

C9H13N5O4P(1-)*Na(1+)

C9H13N5O4P(1-)*Na(1+)

Conditions
ConditionsYield
With sodium hydroxide In water; acetone at 30℃; Reagent/catalyst; Solvent; Temperature;90.6%
chloromethyl isopropyl carbonate
35180-01-9

chloromethyl isopropyl carbonate

(2E)-but-2-enedioic acid
110-17-8

(2E)-but-2-enedioic acid

tenofovir
147127-20-6

tenofovir

tenofovir disoproxyl fumarate
202138-50-9

tenofovir disoproxyl fumarate

Conditions
ConditionsYield
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%
formaldehyd
50-00-0

formaldehyd

tenofovir
147127-20-6

tenofovir

C19H28N10O8P2

C19H28N10O8P2

Conditions
ConditionsYield
Stage #1: formaldehyd With hydrogenchloride In N,N-dimethyl-formamide at 35 - 40℃; for 1h;
Stage #2: tenofovir at 10 - 15℃; for 48h;
89.5%
Diphenyliodonium triflate
66003-76-7

Diphenyliodonium triflate

tenofovir
147127-20-6

tenofovir

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester
379270-35-6

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester

Conditions
ConditionsYield
With triethylamine In toluene Inert atmosphere; Heating;88.3%
diphenyliodonium tetrafluoroborate

diphenyliodonium tetrafluoroborate

tenofovir
147127-20-6

tenofovir

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester
379270-35-6

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester

Conditions
ConditionsYield
With dmap In acetic acid butyl ester Inert atmosphere; Heating;87%
diphenyliodonium bromide
1483-73-4

diphenyliodonium bromide

tenofovir
147127-20-6

tenofovir

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester
379270-35-6

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester

Conditions
ConditionsYield
With toluene In acetic acid butyl ester at 80℃; Inert atmosphere;86.3%
tenofovir
147127-20-6

tenofovir

phenol
108-95-2

phenol

9-[(R)-2-[[(S)-[bis(phenoxy)phosphinyl]]methoxy]propyl]adenine

9-[(R)-2-[[(S)-[bis(phenoxy)phosphinyl]]methoxy]propyl]adenine

Conditions
ConditionsYield
Stage #1: tenofovir With thionyl chloride In acetonitrile at 70℃; for 2h; Inert atmosphere; Large scale;
Stage #2: phenol In acetonitrile at 80℃; for 13h; Large scale;
85%
diphenyliodonium hexafluorophosphate
58109-40-3

diphenyliodonium hexafluorophosphate

tenofovir
147127-20-6

tenofovir

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester
379270-35-6

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester

Conditions
ConditionsYield
With N-ethyl-N,N-diisopropylamine In acetonitrile Inert atmosphere; Heating;84.2%
diphenyliodonium nitrate

diphenyliodonium nitrate

tenofovir
147127-20-6

tenofovir

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester
379270-35-6

((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoric acid monophenyl ester

Conditions
ConditionsYield
With potassium tert-butylate In dichloromethane Inert atmosphere; Heating;80.1%
alanine isopropyl ester hydrochloride
39613-92-8, 62062-56-0, 62062-65-1

alanine isopropyl ester hydrochloride

tenofovir
147127-20-6

tenofovir

P-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}-N-[(1S)-1-methyl-2-(1-methylethoxy)-2-oxoethyl]phosphonamidic acid

P-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}-N-[(1S)-1-methyl-2-(1-methylethoxy)-2-oxoethyl]phosphonamidic acid

Conditions
ConditionsYield
Stage #1: tenofovir With thionyl chloride In toluene at 80 - 90℃; for 20h;
Stage #2: alanine isopropyl ester hydrochloride With sodium sulfate In dichloromethane; toluene at -15℃; for 4h; Inert atmosphere;
80%
With 1,2-dichloro-ethane; triethylamine In water at 20 - 40℃; for 16h; pH=7.2 - 7.6;
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In water at 80 - 90℃; for 48h;

147127-20-6Relevant articles and documents

Rapid, mild method for phosphonate diester hydrolysis: Development of a one-pot synthesis of tenofovir disoproxil fumarate from tenofovir diethyl ester

Houghton, Stephen R.,Melton, Jack,Fortunak, Joseph,Brown Ripin, David H.,Boddy, Christopher N.

, p. 8137 - 8144 (2010)

A rapid, low temperature hydrolysis of tenofovir diethyl ester mediated by TMSCl and NaBr was identified and demonstrated to be superior to the current production method, TMSBr-mediated hydrolysis. This mild phosphonate ester hydrolysis was then coupled to alkylation of the phosphonic acid, providing a one-pot procedure for formation of tenofovir disoproxil from tenofovir diethyl ester. The hydrolytic conditions developed here dramatically improve the synthesis of tenofovir disoproxyl and will lead to lower cost HIV/AIDS treatment in the developing world.

Di- tert-butyl Phosphonate Route to the Antiviral Drug Tenofovir

Dietz, Jule-Philipp,Ferenc, Dorota,Jamison, Timothy F.,Gupton, B. Frank,Opatz, Till

supporting information, p. 789 - 798 (2021/03/01)

Di-tert-butyl oxymethyl phosphonates were investigated regarding their suitability for preparing the active pharmaceutical ingredient tenofovir (PMPA). First, an efficient and simple access to the crystalline di-tert-butyl(hydroxymethyl)phosphonate was developed. O-Mesylation gave high yields of the active phosphonomethylation reagent. For the synthesis of tenofovir, a two-step sequence was developed using Mg(OtBu)2 as the base for the alkylation of (R)-9-(2-hydroxypropyl)adenine. Subsequent deprotection could be achieved with aqueous acids. (Di-tert-butoxyphosphoryl)methyl methanesulfonate showed to be the most efficient electrophile tested, affording PMPA in 72% yield on a 5 g scale. The developed protocol could also be applied for the preparation of the hepatitis B drug adefovir (64% yield/1 g scale).

Repurposing Antiviral Drugs for Orthogonal RNA-Catalyzed Labeling of RNA

Dey, Surjendu,Ghaem Maghami, Mohammad,H?bartner, Claudia,Lenz, Ann-Kathrin

, p. 9335 - 9339 (2020/04/17)

In vitro selected ribozymes are promising tools for site-specific labeling of RNA. Previously known nucleic acid catalysts attached fluorescently labeled adenosine or guanosine derivatives through 2′,5′-branched phosphodiester bonds to the RNA of interest. Herein, we report new ribozymes that use orthogonal substrates, derived from the antiviral drug tenofovir, and attach bioorthogonal functional groups, as well as affinity handles and fluorescent reporter units through a hydrolytically more stable phosphonate ester linkage. The tenofovir transferase ribozymes were identified by in vitro selection and are orthogonal to nucleotide transferase ribozymes. As genetically encodable functional RNAs, these ribozymes may be developed for potential cellular applications. The orthogonal ribozymes addressed desired target sites in large RNAs in vitro, as shown by fluorescent labeling of E. coli 16S and 23S rRNAs in total cellular RNA.

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