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Tuesday 14 October 2014

EFINACONAZOLE , Эфинаконазол ,艾非康唑 , إيفيناكونازول


Efinaconazole.svg
Efinaconazole
(2R,3R)-2-(2,4-Difluorophenyl)-3-(4-methylene-1-piperidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol
(2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidine-1-yl)-1-(1H-1,2,4-triazole-1-yl)-butane-2-ol

EFINACONAZOLE,
KP-103,
cas 164650-44-6, Efinaconazole [INN], UNII-J82SB7FXWB,  AC1LAJ21, Efinaconazole [USAN:INN],
  • Efinaconazole
  • Jublia
  • KP-103
  • UNII-J82SB7FXWB
(2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylidenepiperidin-1-yl)-1-(1,2,4-triazol-1-yl)butan-2-ol
Molecular Formula: C18H22F2N4O   Molecular Weight: 348.390286
Chemical structure for EFINACONAZOLEefinaconazole
 





1H NMR PREDICT


(2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylidenepiperidin-1-yl)-1-(1,2,4-triazol-1-yl)butan-2-ol NMR spectra analysis, Chemical CAS NO. 164650-44-6 NMR spectral analysis, (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylidenepiperidin-1-yl)-1-(1,2,4-triazol-1-yl)butan-2-ol H-NMR spectrum






………………………………………
 13C NMR PREDICT
(2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylidenepiperidin-1-yl)-1-(1,2,4-triazol-1-yl)butan-2-ol NMR spectra analysis, Chemical CAS NO. 164650-44-6 NMR spectral analysis, (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylidenepiperidin-1-yl)-1-(1,2,4-triazol-1-yl)butan-2-ol C-NMR spectrum



 COSY PREDICT

HMBC PREDICT



...............................
 ELABORATION

1H NMR PREDICT




13C NMR



“Drugs at FDA: JUBLIA”. Retrieved 26 June 2014.
NDA Appl No
RLD Active Ingredient Dosage Form; Route Strength Proprietary Name Applicant
N203567
Yes EFINACONAZOLE SOLUTION; TOPICAL 10% JUBLIA DOW PHARM
JUNE6 2014 APPROVED

Patent Data

Appl No Prod No US Patent No Patent
Expiration
Drug Substance
Claim
Drug Product
Claim
Patent Use
Code

N203567 001 7214506 Oct 5, 2021

U – 281
N203567 001 8039494 Jul 8, 2030

U – 281
N203567 001 8486978 Oct 24, 2030
Y

Exclusivity Data

Appl No Prod No Exclusivity Code Exclusivity Expiration
N203567 001 NCE Jun 6, 2019
Efinaconazole is a triazole antifungal. It is approved for use in Canada as 10% topical solution for the treatment of onychomycosis (fungal infection of the nail).[1][2] Efinaconazole acts as a 14α-demethylase inhibitor.[3]


PATENT
Figure US20130150586A1-20130613-C00002
Example 1Production of (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidin-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol (KP-103)21.26 g (119.4 mmol) of the 4-methylenepiperidine hydrobromide (4-MP.HBr) obtained in Production 1 and 2.859 g (119.4 mmol) of lithium hydroxide were added to 80 mL of acetonitrile and stirred for a while. Thereafter, 20 g (79.6 mmol) of (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]oxirane was added and the mixture was heated under reflux in an oil bath (external temperature: 100° C.) for 14 hours. After the reaction completed, ethanol and distilled water were added to the reaction mixture, whereupon a crystal was precipitated. Thereafter, the crystal was filtered off, washed with 40 mL of an ethanol/water mixture, dried with air at room temperature and further dried under reduced pressure at 40° C. for 12 hours to give a pale yellow crystal of KP-103 in an amount of 24.2 g (yield, 87.3%; purity on HPLC, 95.3%).

1H-NMR (500 MHz, CDCl3)δ: 0.96 (3H, dd, J=2.68, 7.08 Hz), 2.13-2.26 (4H, m), 2.35 (2H, br), 2.70 (2H, br), 2.90-2.94 (1H, q, J=7.08 Hz), 4.64 (2H, s), 4.82 (1H, dd, J=0.73, 14.39 Hz), 4.87 (1H, dd, J=0.73, 14.39 Hz), 5.45 (1H, s), 6.72-6.81 (2H, m), 7.51 (1H, dt, J=6.59, 9.03 Hz), 7.78 (1H, s), 8.02 (1H, s).
FAB-MS m/z: 349 [M+H]+
melting point: 86-89° C.
optical rotation: [α]D 25 −87 to −91° (C=1.0, methanol)
………………………………….
Journal of Organic Chemistry, 2014 ,  vol. 79,   7  pg. 3272 – 3278
A new synthetic route, the shortest reported to date, to access a key intermediate for the synthesis of various triazole antifungal agents was developed. The elusive tetrasubstituted stereogenic center that is essential in advanced triazole antifungal agents was constructed via the catalytic asymmetric cyanosilylation of a ketone. The subsequent transformations were performed in two one-pot operations, enhancing the overall synthetic efficiency toward the intermediate. This streamlined synthetic approach was successfully applied to efficient enantioselective syntheses of efinaconazole (Jublia) and ravuconazole.
Figure
Scheme 3. Synthesis of Efinaconazole (Jublia)
(2R,3R)-2-(2,4-Difluorophenyl)-3-(4-methylenepiperidin-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol (Efinaconazole)
To a solution of 1 (54.2 mg, 0.216 mmol) in EtOH (217 μL) was added 4-methylenepiperidine (147 mg, 1.51 mmol), ……………………deleted………………. see original…………….. was purified using silica gel column chromatography (CHCl3/MeOH = 10:1) to give 67.6 mg ofefinaconazole (90% yield) as a colorless amorphous solid.

[α]D20 −87.8 (c 1.12, CHCl3);
1H NMR (400 MHz, CDCl3) δ 8.00 (s, 1H), 7.76 (s, 1H), 7.51–7.45 (m, 1H), 6.78–6.68 (m, 2H), 5.50 (brs, 1H), 4.85 (d,J = 14.4 Hz, 1H), 4.78 (d, J = 14.4 Hz, 1H), 4.61 (s, 2H), 2.88 (q, J = 6.9 Hz, 1H), 2.66 (br s, 2H), 2.32 (br s, 2H), 2.21–2.17 (m, 4H), 0.93 (dd, J = 6.9, 2.1 Hz, 3H);

13C NMR (150 MHz, CDCl3) δ 162.5 (dd, J = 250, 13 Hz), 158.5 (dd, J = 246, 12 Hz), 151.3, 145.9, 144.4, 130.6 (dd, J = 8.7, 5.8 Hz), 124.7 (dd, J= 14, 3.6 Hz), 111.4 (dd, J = 20, 2.9 Hz), 108.1, 104.1 (dd, J = 28, 25 Hz), 77.7 (d, J = 5.8 Hz), 64.4, 55.9 (d, J = 8.7 Hz), 52.4, 35.2, 7.63 (d, J = 2.9 Hz);

19F NMR (376 MHz, CDCl3) δ −105.8, −110.7;

IR (CHCl3, cm–1) ν 3423, 3073, 2979, 2939, 2899, 2810, 1615, 1498, 1418, 1273, 1138;

HRMS (ESI-TOF) calcd for C18H23ON4F2 [M + H]+ m/z 349.1834, found 349.1828.
……………

SYN
http://newdrugapprovals.org/2014/06/10/valeant-pharmaceuticals-announces-fda-approval-of-jublia-for-the-treatment-of-onychomycosis/


updated
1H NMR

Displaying image001.png

get clear pic at........http://pubs.acs.org/doi/suppl/10.1021/jo500369y/suppl_file/jo500369y_si_001.pdf

13C NMR


Displaying image002.png
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Khajuraho Group of Monuments is located in India
Khajuraho Group of Monuments
Location of Khajuraho Group of Monuments in India.

Location in Madhya PradeshLocation in Madhya Pradesh

  1. Khajuraho Group of Monuments - Wikipedia, the free ...

    en.wikipedia.org/wiki/Khajuraho_Group_of_Monuments

    The Khajuraho Group of Monuments are a group of Hindu and Jain temples in Madhya Pradesh, India. About 620 kilometres (385 mi) southeast of New Delhi, ...























Hotel Chandela - A Taj Leisure Hotel



















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09b37-misc2b027LIONEL MY SON
He was only in first standard in school when I was hit by a deadly one in a million spine stroke called acute transverse mylitis, it made me 90% paralysed and bound to a wheel chair, Now I keep him as my source of inspiration and helping millions, thanks to millions of my readers who keep me going and help me to keep my son happy




Friday 10 October 2014

Nabriva’s lefamulin, BC 3781

Nabriva’s lefamulin, BC 3781

2D chemical structure of 1061872-97-6
Nabriva’s lefamulin receives FDA fast-track status to treat CABP and ABSSS
Austria-based Nabriva Therapeutics has received qualified infectious disease product (QIDP) and fast-track status designation from the US Food and Drug Administration for its lefamulin (BC 3781).
read
Antibiotics 02 00500 i025
BC-3781
Topical pleuromutilin antibiotic agent
Gram-positive, including MRSA, PHASE 2 COMPLETED,Infection, acute bacterial skin and skin structure (ABSSSI)
Nabriva (Austria), Nabriva Therapeutics AG
BC-3781
cas 1061872-97-6
UNII-61H04Z5F9K
(3aS,4R,5S,6S,8R,9R,9aR,10R)-5-Hydroxy-4,6,9,10-tetramethyl-1-oxo-6-vinyldecahydro-3a,9-propanocyclopenta[8]annulen-8-yl [[(1R,2R,4R)-4-amino-2-hydroxycyclohexyl]sulfanyl]acetate;
14-O-[2-[(1R,2R,4R)-4-Amino-2-hydroxycyclohexylsulfanyl]acetyl]mutilin

lH NMR (400 MHz, CDC13, ppm, inter alia) δ 6.51 – 6.44 (m, 1H), 5.78 (d, J=8Hz, 1H), 5.38 – 5.20 (m, 2H), 3.48 – 3.40 (m, 1H), 3.36 (d, J=7Hz, 1H), 3.25 (AB, J=15Hz, 2H), 2.92 – 2.82 (m, 1H), 2.6 – 2.5 (m, 1H), 1.45 (s, 3H), 1.20 (s, 3H), 0.88 (d, J=7Hz, 3 H), 0.73 (d, J=8Hz, 3H)
MS (ESI, g/mol): m/z 508 [M+H] +

Tuesday 7 October 2014

Applications of Mass Spectrometry...on November 20, 2014 at CSIR-Indian Institute of Chemical Technology, Hyderabad, India


AMS14.jpg







Dr Sanjay Bajaj





Dr Sanjay Bajaj
Managing Director at Select Biosciences India

or see
http://selectbiosciences.com/conferences/index.aspx?conf=AMS14

SELECTBIO welcome you all at the International Conference on Applications of Mass Spectrometry scheduled to be held on November 20, 2014 at CSIR-Indian Institute of Chemical Technology, Hyderabad, India

Mass Spectrometry, has now become the most powerful analytical tool in almost every scientific discipline. This conference focuses on the instrumentation, tools, interpretation of results, applications, advances and new perspectives of Mass Spectrometry in the fields of Pharmaceuticals, Clinical, Genomics, Proteomics, Forensic, Environmental sciences etc. Attending this event will provide you with excellent opportunity for networking with like minded peers, helping you to build new relationships and optimize your workflow. 

This event is co-located with specialized event related to use of Mass Spectrometry in Pharmaceutical Analysis i.e.Advances in Forced Degradation Studies of Pharmaceuticals. Running alongside the conference will be an exhibition covering the latest technological advances and associated services within this field. 

Confirmed Speakers to date

Saranjit Singh, Professor/Head, National Institute of Pharmaceutical Education and Research
Jurgen H Gross, Head Mass Spectrometry Lab, Heidelberg University
R Srinivas, Head, NCMS, Indian Institute of Chemical Technology
Utpal Tatu, Professor, Indian Institute of Science
Mariappanadar Vairamani, Dean, SRM University

Call for Posters

You can also present your research on a poster while attending the meeting. Submit an abstract for consideration now!
Poster Submission Deadline: 31 October 2014

Agenda Topics

  • Applications in Genomics, Proteomics, Metabolomics & Lipidomics
  • In Lab Mass Spectrometry Workshop
  • Mass Spectrometry – Instrumentation and tools
  • Mass Spectrometry for Qualitative and Quantitative Analysis of Pharmaceuticals
  • Mass Spectrometry-Current Approaches and New Vistas

Sponsorship and Exhibition Opportunities

Maninderjit Singh, Exhibition Manager
mjsingh@selectbio.com
7696225050

Thursday 2 October 2014

2-PENTANONE



2-PENTANONE

1) In the NMR spectrum, we note that there are 4 distinct peaks, so we know that in the molecule, there are four different types of hydrogens.
2) The area of the individual peaks gives the sum of 10, in line with the empirical formula C 5 H 10 O, so the area declared at the top of the peaks corresponds to the number of hydrogen atoms that produce that signal.
3) The molecule C 5 H 10 O contains a double bond, in fact if it were saturated with hydrogens would contain 12 (2n + 2). Because it contains a carbonyl, the double bond is here, the rest of the molecule is saturated.
4) The two signals at d 2.45 and d 2.09 corresponding to the hydrogens on the carbon next to the carbonyl which absorb in the range between d 2 and d 3. The other two peaks at d 0.96 and d 1.61 corresponding to hydrogen instead of carbon primary and secondary respectively.
5) The peak 2 at d 2.09 has multiplicity 1 then refers to hydrogens that do not have near no hydrogen (m - 1 0 = H). This confirms the previous inference that the peak is due to a CH 3 near the bunker.

The peak 1 at d 2.45 has multiplicity 3 then refers to hydrogens which have close idogeni 2 (m - 1 = 2 H). This confirms the previous inference that the peak is attributable to a CH 2 near a bunker, and also suggests that there is a further CH 2 tied immediately over.

The peak 3 at d 1.61 has multiplicity 6 then refers to hydrogens that are near 5 hydrogens (m - 1 = 5 H). This confirms the previous inference that the peak is due to a CH 2 secondary that has near the two hydrogens of the peak 1 and the other three hydrogen atoms, those of the CH 3terminal.

The peak 4 at d 0.96 has multiplicity 3 then refers to hydrogens which have close idogeni 2 (m - 1 = 2 H). This confirms the previous inference that the peak is due to the CH 3 terminal of the molecule.

6)
 The deductions made ​​so far lead us to hypothesize that the NMR spectrum is related to the molecule 2-pentanone which has the structure shown at right:

7)
 Analyzing the molecule of 2-pentanone we can confirm the assignment of the peaks for both the chemical shift, both for the multiplicity (indicated in the figure in parentheses.)
 
2-pentanone




IR



MASS



13 CNMR




RAMAN