DR ANTHONY MELVIN CRASTO,WorldDrugTracker, helping millions, A 90 % paralysed man in action for you, I am suffering from transverse mylitis and bound to a wheel chair, With death on the horizon, nothing will not stop me except God................DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai) , INDIA 25Yrs Exp. in the feld of Organic Chemistry,Working for GLENMARK GENERICS at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.Million hits on google, world acclamation from industry, academia, drug authorities for websites, blogs and educational contribution

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
DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

Join me on Linkedin

View Anthony Melvin Crasto Ph.D's profile on LinkedIn

Join me on Facebook FACEBOOK
Join me on twitterFollow amcrasto on Twitter     
Join me on google plus Googleplus

 amcrasto@gmail.com




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



















DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE


Join me on Linkedin

View Anthony Melvin Crasto Ph.D's profile on LinkedIn

Join me on Facebook FACEBOOK
Join me on twitterFollow amcrasto on Twitter     
Join me on google plus Googleplus

 amcrasto@gmail.com

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




No comments:

Post a comment