Tenofovir Disoproxil Fumarate

Tenofovir Disoproxil Fumarate
SYN...........
https://newdrugapprovals.org/2016/03/15/an-improved-process-for-the-preparation-of-tenofovir-disoproxil-fumarate/
 NMR.........http://file.selleckchem.com/downloads/nmr/s140001-tenofovir-disoproxil-fumarate-hnmr-selleck.pdf

 
WO2014035064A1...Figure 7 is the ¹H nuclear magnetic resonance (NMR) spectrum of tenofovir disoproxil fumarate

 PAPER

Journal of Pharmaceutical and Biomedical Analysis

Volume 107, 25 March 2015, Pages 175–185

Isolation, LC–MS/MS and 2D-NMR characterization of alkaline degradants of tenofovir disoproxil fumarate

• Vaibhav Anandgaonkar^a,
• Abhishek Gupta^{b, ,} ,
• Srinivas Kona^b,
• M.V.N. Kumar Talluri^{a, , ,}

• ^a Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, India
• ^b Analytical Chemistry Division, Daiichi Sankyo Life Sciences Research Centre in India (RCI), Gurgaon 122015, India

 http://www.sciencedirect.com/science/article/pii/S0731708514006414

1. 
2. 
3. Table 1
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6. 
7. Table 2
8. Table 3
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18. 

PAPER

The current three-step manufacturing route for the preparation of tenofovir disoproxil fumarate (1) was assessed and optimized leading to a higher yielding, simpler, and greener process. Key improvements in the process route include the refinement of the second stage through the replacement of the problematic magnesium tert-butoxide (MTB) with a 1:1 ratio of a Grignard reagent and tert-butanol. The development of a virtually solvent-free approach and the establishment of a workup and purification protocol which allows the isolation of a pure diethyl phosphonate ester (8) was achieved

see.............http://pubs.acs.org/doi/abs/10.1021/acs.oprd.5b00364

An Improved Process for the Preparation of Tenofovir Disoproxil Fumarate

Darren L. Riley^*†∥, David R. Walwyn^‡∥, and Chris D. Edlin^§∥

^† Department of Chemistry, Natural and Agricultural Sciences, University of Pretoria, 2 Lynnwood Road, Hatfield, 0002, Gauteng, South Africa

^‡ Department of Engineering and Technology Management, University of Pretoria, Pretoria, South Africa

^§ Pharmaceutical Manufacturing Technology Centre, University of Limerick, Limerick, V94 T9PX, Republic of Ireland

^∥ iThemba Pharmaceuticals, Modderfontein, 1645, Gauteng South Africa

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.5b00364

Publication Date (Web): March 04, 2016

Copyright © 2016 American Chemical Society

*E-mail: darren.riley@up.ac.za.

• 
  University of Pretoria

  Department of Chemistry

  Pretoria, South Africa

Department of Chemistry, Natural and Agricultural Sciences, University of Pretoria, 2 Lynnwood Road, Hatfield, 0002, Gauteng, South Africa




PAPER........http://www.hindawi.com/journals/jchem/2013/126502/
 Journal of Chemistry
Volume 2013 (2013), Article ID 126502, 12 pages
http://dx.doi.org/10.1155/2013/126502

Research Article
Vibrational Spectroscopic Studies of Tenofovir Using Density Functional Theory Method
G. R. Ramkumaar,1 S. Srinivasan,2 T. J. Bhoopathy,1 and S. Gunasekaran1

1PG and Research Department of Physics, Pachaiyappa's College, Chennai 600030, India
2PG and Research Department of Physics, Presidency College, Chennai 600005, India


A B

 C


 D
 Figure 3: Theoretical and experimental IR spectrum of tenofovir.



 Figure 4: FT-Raman spectrum of tenofovir.


T able 6: The calculated 13C and 1H NMR chemical shifts of tenofovir.
Atom position    B3LYP/6-311++    B3LYP/6-31    B3PW91/6-31    ChemDraw Ultra    Assignment
Absolute shielding    Chemical shift    Absolute shielding    Chemical shift    Absolute shielding    Chemical shift          
1    114.7    85.3    126.6    73.3    129.7    70.3    73.4    C1 in Aliphatic
3    124.7    75.3    136.6    63.4    139.3    60.7    58.6    C3 in Aliphatic
4    122.5    77.4    134.7    65.3    137.5    62.4    76    C4 in Aliphatic
5    153.9    46.1    163.3    36.7    166.4    33.6    20    C5 in Aliphatic
7    36.4    163.5    56.7    143.3    58.8    141.1    143    C7 in Purine
9    25.3    174.7    44.9    155.1    47.3    152.6    149.8    C9 in Purine
11    23.0    177.0    42.9    157.1    45.1    154.9    152.4    C11 in Purine
13    33.6    166.4    55.0    144.9    56.9    143.1    156.1    C13 in Purine
14    62.8    137.2    81.3    118.6    83.6    116.4    119.4    C14 in Purine
20    27.8    4.8    28.0    4.6    27.9    4.7    3.4    H20 in Methylene
21    27.9    4.7    28.0    4.6    28.0    4.6    3.4    H21 in Methylene
22    27.5    5.1    27.5    5.1    27.4    5.2    3.9    H22 in Methylene
23    26.8    5.8    26.7    5.9    26.6    6.0    3.7    H23 in Methyene
24    16.4    16.2    16.3    16.3    16.2    16.4    12.0    H24 in Methine
25    29.7    2.9    29.7    2.9    29.6    3.0    1.2    H25 in Methyl
26    30.3    2.3    30.2    2.4    30.2    2.4    1.2    H26 in Methyl
27    30.3    2.3    30.3    2.3    30.2    2.4    1.2    H27 in Methyl
28    23.8    8.8    23.8    8.8    23.6    9.0    8.1    H28 in Purine
29    23.3    9.3    23.1    9.5    22.9    9.7    8.2    H29 in Purine
30    25.0    7.6    25.2    7.4    25.0    7.6    7.0    H30 in Aromatic
31    25.6    7.0    25.9    6.7    25.7    6.9    7.0    H31 in Aromatic
32    29.2    3.4    29.0    3.6    28.9    3.7    12.0    H32 in Alcohol
33    28.3    4.3    28.2    4.4    28.1    4.5    12.0    H33 in Alcohol

 

(a)

(b)
Figure 5: (a) 13C NMR spectrum of tenofovir. (b) 1H NMR spectrum of tenofovir.

Tenofovir disoproxil

Systematic (IUPAC) name
Bis{[(isopropoxycarbonyl)oxy]methyl} ({[(2R)-1-(6-amino-9H-purin-9-yl)-2-propanyl]oxy}methyl)phosphonate
Clinical data
Trade names	Viread
AHFS/Drugs.com	monograph
Pregnancy category	AU: B3 US: B (No risk in non-human studies)
Routes of administration	Oral (tablets)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	25%
Identifiers
CAS Number	201341-05-1
ATC code	J05AF07 (WHO)
PubChem	CID 5481350
ChemSpider	4587262
UNII	F4YU4LON7I
ChEBI	CHEBI:63717
NIAID ChemDB	080741
Chemical data
Formula	C19H30N5O10P
Molar mass	519.443 g/mol
SMILES[show]
InChI[show]

Tenofovir

Systematic (IUPAC) name
({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonic acid
Clinical data
MedlinePlus	a602018
Routes of administration	In form of prodrugs
Pharmacokinetic data
Protein binding	< 1%
Biological half-life	17 hours
Excretion	Renal
Identifiers
CAS Number	147127-20-6
ATC code	None
PubChem	CID 464205
DrugBank	DB00300
ChemSpider	408154
UNII	99YXE507IL
KEGG	D06074
ChEBI	CHEBI:63625
ChEMBL	CHEMBL483
Synonyms	9-(2-Phosphonyl-methoxypropyly)adenine (PMPA)
Chemical data
Formula	C9H14N5O4P
Molar mass	287.213 g/mol

SEE........ http://www.ijcps.com/files/vol3issue3/17.pdf
http://shodhganga.inflibnet.ac.in/bitstream/10603/18837/5/05_chapter%203.pdf
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