EFINACONAZOLE , Эфинаконазол ,艾非康唑 , إيفيناكونازول

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

efinaconazole

 

1H NMR PREDICT

………………………………………
 13C NMR PREDICT

 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

http://www.google.com/patents/US20130150586

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

http://pubs.acs.org/doi/abs/10.1021/jo500369y

http://pubs.acs.org/doi/suppl/10.1021/jo500369y/suppl_file/jo500369y_si_001.pdf

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.

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.

http://pubs.acs.org/doi/suppl/10.1021/jo500369y/suppl_file/jo500369y_si_001.pdf

……………

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


updated
1H NMR



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

13C NMR

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

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Nabriva’s lefamulin, BC 3781

Nabriva’s lefamulin, BC 3781

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

http://www.pharmaceutical-technology.com/news/newsnabrivas-lefamulin-receives-fda-fast-track-status-to-treat-cabp-and-absssi-4399182?WT.mc_id=DN_News

 http://newdrugapprovals.org/2014/10/10/nabrivas-lefamulin-bc-3781-receives-fda-fast-track-status-to-treat-cabp-and-absssi/

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

http://newdrugapprovals.org/2014/10/10/nabrivas-lefamulin-bc-3781-receives-fda-fast-track-status-to-treat-cabp-and-absssi/

http://www.google.com/patents/WO2008113089A1?cl=en

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] +

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

Dr Sanjay Bajaj
Managing Director at Select Biosciences India

Limited seats available for In-Lab Workshop on Mass Spectrometry. Register today to avoid disappointments for "Applications of Mass Spectrometry" conference scheduled to be held on Nov 20, 2014 at CSIR-IICT, Hyderabad. For more information follow the linkhttp://lnkd.in/bJg6ai6

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

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

(S)-Atenolol

(S)-Atenolol

• Selective β1 adrenoceptor antagonist
• Biological descriptionSelective β1 adrenoceptor antagonist. Orally active. Limited ability to cross the blood-brain barrier. Antihypertensive activity in vivo.

Properties

• Chemical name(S)-(-)-4-[2-Hydroxy-3-[(1-methylethyl)amino]propoxy]benzeneacetamide
• Molecular Weight 266.34
• Molecular formula C14H22N2O3
• CAS Number 93379-54-5

US6982349

Emcure Pharmaceuticals Limited

http://www.google.com/patents/US6982349

Satish Ramanlal Mehta, Baburao Manikroa Bhawal, Vishnu Hari Deshpande,Mukund Keshav Gurjar

m.p. 152–153° C.

[α]D 25: −17.2 (c=1.0, 1N HCl).

IR: νmax 3352, 3168, 1635, 1242 cm−1.

1H NMR (DMSO-d6): δ 0.99 (d, J=7 Hz, 6H, 2×CH3), 2.60 (m, 1H, CH), 2.74 (m, 2H, CH2), 3.27 (s, 2H, CH2), 3.88 (m, 4H, CH2, CH, NH), 6.83 (d, J=8 Hz, 2H, Ar—H), 7.14 (d, J=8 Hz, 2H, Ar—H), 7.40 (bs, 1H).

13C NMR (DMSO-d6):
22.01, 22.09,
41.26, 48.39, 49.38, 67.73, 70.58, 114.16, 128.41, 129.93, 157.17, 172.59 ppm.

COBICISTAT

Cobicistat, GS-9350

1004316-88-4

C 40 H 53 N 7 O 5 S 2

N-[1(R)-Benzyl-4(R)-[2(S)-[3-(2-isopropylthiazol-4-ylmethyl)-3-methyl]ureido]-4-(4-morpholinyl)butyramido]-5-phenylpentyl]carbamic acid thiazol-5-ylmethyl ester

(1,3-thiazol-5-yl) methyl (5S, 8R, 11R) -8,11-dibenzyl-2-methyl-5-[2 - (morpholin-4-yl) ethyl] -1 – [2 - (propan-2-yl) -1,3-thiazol-4-yl] -3,6-dioxo-2 ,4,7,12-tetraazatridecan-13-oate

cytochrome P450 3A4 (CYP3A4) inhibitor

Gilead Sciences, Inc.

SEE SYNTHESIS AT
http://newdrugapprovals.org/2014/09/26/fda-approves-tybost-cobicistat-for-use-in-the-treatment-of-hiv-1-infection/http://newdrugapprovals.org/2014/09/26/fda-approves-tybost-cobicistat-for-use-in-the-treatment-of-hiv-1-infection/

Cobicistat (GS-9350): A potent and selective inhibitor of human CYP3A as a novel pharmacoenhancer
ACS Med Chem Lett 2010, 1(5): 209

http://pubs.acs.org/doi/abs/10.1021/ml1000257

http://pubs.acs.org/doi/suppl/10.1021/ml1000257/suppl_file/ml1000257_si_001.pdf

1-Benzyl-4-{2-[3-(2-isopropyl-thiazol-4-ylmethyl)-3-methyl-ureido]-4-morpholin-4-yl-butyrylamino}-5-phenyl-pentyl)-carbamic acid thiazol-5-ylmethyl ester (GS-9350)

HPLC (Chiral CelROD-H, Chiral Technologies Inc;heptane/iPrOH = 70/30).

1H NMR (CD3OD)

δ8.98 (1 H, s), 7.82 (1 H, s), 7.25-7.05

(11 H, m), 5.25-5.10 (2 H, m), 4.60-4.50 (2 H, m), 4.21-4.03 (2 H, m), 3.82-3.72 (1

H, m), 3.65-3.65 (4 H, m), 3.35-3.25 (1 H, m), 2.98 (3 H, s), 2.8-2.6 (4 H, m), 2.4-2.2

(6 H, m), 1.95-1.8 (1 H, m), 1.8-1.6 (1 H, m), 1.6-1.4 (4 H, m), 1.42-1.32 (6 H, m).

MS (ESI) m/z: 776.2 (M+H)+.

HRMS calc. for C40H53N7O5S2: 775.355, found: 775.353.

US 2014088304

http://www.google.com/patents/US20140088304

The product I was isolated as the stock solution in ethanol (35.0 kg product, 76.1% yield).

¹H NMR (^dDMSO) δ□ 9.05 (s, 1H), 7.85 (s, 1H), 7.52 (d, 1H), 7.25-7.02 (m, 12H), 6.60 (d, 1H), 5.16 (s, 2H), 4.45 (s, 2H), 4.12-4.05 (m, 1H), 3.97-3.85 (m, 1H), 3.68-3.59 (m, 1H), 3.57-3.45 (m, 4H), 3.22 (septets, 1H), 2.88 (s, 3H), 2.70-2.55 (m, 4H), 2.35-2.10 (m, 6H), 1.75 (m, 1H), 1.62 (m, 1H), 1.50-1.30 (m, 4H), 1.32 (d, 6H).

¹³C NMR (CD₃OD) δ 180.54, 174., 160.1, 157.7, 156.9, 153.8, 143.8, 140.1, 140.0, 136.0, 130.53, 130.49, 129.4, 127.4, 127.3, 115.5, 67.7, 58.8, 56.9, 55.9, 54.9, 53.9, 51.6, 49.8, 42.7, 42.0, 35.4, 34.5, 32.4, 32.1, 29.1, 23.7.

MAKE IN INDIA
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Synthesis, biological evaluation and docking analysis of 3-methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones as potential cyclooxygenase-2 (COX-2) inhibitors

COMPD HAS  cas no 1616882-93-9

MF……….C18 H11 F3 N2 O2

[1]​Benzopyrano[4,​3-​c]​pyrazol-​4(1H)​-​one, 3-​methyl-​1-​[4-​(trifluoromethyl)​phenyl]​-

 3-Methyl-1-(4-(trifluoromethyl)phenylchromeno[4,3-c]pyrazol-4(1H)-one

Synthesis, biological evaluation and docking analysis of 3-methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones as potential cyclooxygenase-2 (COX-2) inhibitors

Bioorganic & Medicinal Chemistry Letters,Volume 24, Issue 19, 1 October 2014, Pages 4638–4642

DOI: 10.1016/j.bmcl.2014.08.050

Jagdeep Grover, Vivek Kumar, M. Elizabeth Sobhia, Sanjay M. Jachak

http://www.sciencedirect.com/science/article/pii/S0960894X14008944

 Abstract

As a part of our continued efforts to discover new COX inhibitors, a series of 3-methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones were synthesized and evaluated for in vitro COX inhibitory potential. Within this series, seven compounds (3a–d, 3h, 3k and 3q) were identified as potential and selective COX-2 inhibitors (COX-2 IC50’s in 1.79–4.35 μM range; COX-2 selectivity index (SI) = 6.8–16.7 range). Compound 3b emerged as most potent (COX-2 IC50 = 1.79 μM; COX-1 IC50 >30 μM) and selective COX-2 inhibitor (SI >16.7). Further, compound 3b displayed superior anti-inflammatory activity (59.86% inhibition of edema at 5 h) in comparison to celecoxib (51.44% inhibition of edema at 5 h) in carrageenan-induced rat paw edema assay. Structure–activity relationship studies suggested that N-phenyl ring substituted with p-CF3 substituent (3b, 3k and 3q) leads to more selective inhibition of COX-2. To corroborate obtained experimental biological data, molecular docking study was carried out which revealed that compound 3b showed stronger binding interaction with COX-2 as compared to COX-1.

Authors

• Jagdeep Grovera,
• Vivek Kumarb,
• M. Elizabeth Sobhiab,
• Sanjay M. Jachaka, , ,

• a Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar (Mohali) 160062, Punjab, India
• b Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar 160062, Punjab, India

Sanjay Corresponding author. Tel.: +91 172 2214683; fax: +91 172 2214692.

 CLICK……….

• Supplementary data

Cyclooxygenase (COX) or prostaglandin endoperoxide synthase (PGHS), catalyzes the conversion of arachidonic acid to inflammatory mediators such as prostaglandins (PGs), prostacyclins and thromboxanes. COX exists in mainly two isoforms: COX-1 and COX-2.Nonsteroidal anti-inflammatory drugs (NSAIDs), widely used for relief of fever, pain and inflammation, act by inhibiting COX catalyzed biosynthesis of inflammatory mediators.

However, the therapeutic use of classical NSAIDs is associated with well-known side effects at the gastrointestinal level (mucosal damage, bleeding) and, less frequently, at the renal level.

Two decades after the discovery of COX isoforms, it was recognized that selective inhibition of COX-2 might be endowed with improved anti-inflammatory properties and reduced gastrointestinal toxicity profiles than classical NSAIDs.

Overall, these selective COX-2 inhibitors (coxibs) have fulfilled the hope of possessing reduced risk in gastrointestinal events, but unfortunately cardiovascular concerns regarding the use of these agents have emerged that led to the withdrawal of rofecoxib (Vioxx) and valdecoxib (Bextra) from the market in 2004 and 2005, respectively.

Ongoing safety concerns pertaining to the use of non-selective NSAIDs have spurred development of coxibs with improved safety profile.

……………………………………………………………………………………………..

cas no 1616882-93-9

mf……….C18 H11 F3 N2 O2

[1]​Benzopyrano[4,​3-​c]​pyrazol-​4(1H)​-​one, 3-​methyl-​1-​[4-​(trifluoromethyl)​phenyl]​-

 3-Methyl-1-(4-(trifluoromethyl)phenylchromeno[4,3-c]pyrazol-4(1H)-one

Scheme 1.

Reagent and conditions: (a) Piperidine, rt, 20 min; (b) ArNHNH2, EtOH, reflux, 5 h; (c) K2CO3, acetone, reflux, 24 h.

COMPD IS

3b

R1=H

R2= H

4-CF3-C6H4

90

3-Methyl-1-(4-(trifluoromethyl)phenylchromeno[4,3-c]pyrazol-4(1H)-one (3b):

White solid; yield 90%; mp: 224–225 °C;

1H NMR (CDCl3, 400 MHz): δ ppm 7.89 (d, 2H, J = 8.32 Hz, Ar-H), 7.73 (d, 2H, J = 8.24 Hz, Ar-H), 7.45–7.52 (m, 2H, H-6, H-7), 7.16 (dd, 1H, J = 1.4, 8.2 Hz, H-9), 7.10 (td, 1H, J = 1.56, 7.38 Hz, H-8), 2.69 (s, 3H, CH3);

13C NMR (CDCl3, 100 MHz): δ ppm 157.7, 153.3, 151.5, 142.3, 141.8, 131.9, 127.2, 127.1, 127.0, 124.0, 122.2, 118.3, 111.5, 107.1, 12.8;

HRMS (ESI) m/z: Calcd for C18H11F3N2O2Na [M + Na]+ 367.0670; found 367.0676.

Synthetic Communications (2014), 44(13), 1914-1923

DOI:

10.1080/00397911.2013.879184

Jagdeep Grovera, Somendu Kumar Roya & Sanjay Madhukar Jachaka*

pages 1914-1923

http://www.tandfonline.com/doi/abs/10.1080/00397911.2013.879184#.VCI5f0DgXXM

http://www.tandfonline.com/doi/suppl/10.1080/00397911.2013.879184/suppl_file/lsyc_a_879184_sm8537.pdf

Abstract

Unprecedented cyclization was observed during N-sulfonylation of 3-[1-(phenylhydrazono)-ethyl]-chromen-2-one in pyridine, affording 3-methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones. To avoid use of noxious pyridine, reaction was tried in different basic conditions and the best results were obtained with potassium carbonate in acetone. A wide range of substrates bearing either electron-donating or electron-withdrawing substituents on phenylhydrazine ring were compatible with the developed methodology. Rapid access of starting material, 3-acetylcoumarin, excellent yields of products, and use of environmentally benign base and solvent for the cyclization make this strategy an efficient and convenient method for synthesis of 3-methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones.

Methyl-1-(4-(trifluoromethyl)phenylchromeno[4,3-c]pyrazol-4(1H)-one (4b):

Whitesolid;

yield 90%; mp: 224–225 °C;

1H NMR (CDCl3, 400 MHz):δppm 
2.69 (s, 3H, CH3),

7.10(td, 1H,J= 1.56, 7.38 Hz, H-8),

7.16 (dd, 1H,J= 1.4, 8.2 Hz, H-9),

7.45–7.52 (m, 2H, H-6, H-7),

7.73 (d, 2H,J= 8.24 Hz, Ar-H),

7.89 (d, 2H,J= 8.32 Hz, Ar-H);

13C NMR (CDCl3, 100MHz):

δppm
12.8, 
107.1, 
111.5, 
118.3, 
122.2, 
124.0,

127.0, 
127.1, 
127.2, 
131.9, 
141.8, 
142.3,

151.5, 
153.3, 
157.7;

HRMS (ESI)m/z: Calcd for C18H11F3N2O2Na [M + Na]+367.0670; found367.0676.

 3-Methyl-1-(4-(trifluoromethyl)phenylchromeno[4,3-c]pyrazol-4(1H)-one

SEE BELOW  1H NMR, 13CNMR, AND MASS SPEC

13C NMR




MASS

References
1. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. J. Mol. Biol. 1997, 267, 727.
2. Bernstein, F. C.; Koetzle, T. F.; Williams, G. J. B.; Meyer, E. F.; Brice, M. D.; Rodgers, J. R.; Kennard, O.; Shimanouchi, T.; Tasumi, M. J. Mol. Biol. 1977, 112, 535.

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