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

Sunday 29 November 2015

Surprises in the Study of Ruthenium-catalyzed Stereo- and Chemoselective Aldolizations

http://www.orientjchem.org/wp-content/uploads/2015/10/Vol31_No4_Sur_Elah_Sch1.jpg.

 Typical procedure for ruthenium-catalyzed aldol reaction
A mixture of aldehyde (1 mmol), ketone (3 mmol), RuCl3.nH2O(0.02 mmol) and KOH (28 mg, 0.5 mmol) was stirred at 15 °C and monitored by TLC. After the indicated reaction time, the reaction mixture was purified by thin layer chromatography (silica gel, EtOAc-petroleum ether, 4:12) providing the aldol adduct.

Selected Spectral Data of the Products
Product (3aa)
Yellow oil; FT-IR (neat) (υmax/cm-1): 1666, 3415. Only syn isomer was isolated. 1H NMR (500 MHz, CDCl3): δH(ppm) 1.69-2.65 (m, 7H), 2.52 (s, 3H), 3.03 (d, J = 3.2 Hz, OH), 5.39 (m, 1H), 7.28 (m, 4H). 13C NMR (125 MHz, CDCl3): δC(ppm) 12.2, 14.0, 14.9, 41.1, 58.1, 72.2, 126.5, 128.5, 133.5, 135.2, 218.4. Anal Calcd for C13H16O2S (236): C, 66.10; H, 6.77; S, 13.55. Found: C, 66.10; H, 6.79; S, 13.56.


Table 1: Ruthenium-catalyzed cross aldol reactions of aldehydes with cycloalkanones 3aa-ec.
Entrya R Aldol Yield (%)b Time (h)
1 1a 4-MeSC6H4 3aa 81 5
2 1b 3-Methylthiophen-2-yl 3ba 86 1.5
3 1c 5-Methylthiophen-2-yl 3ca 83 1
4 1d Thiophen-2-yl 3da 91 3
5 1a 4-MeSC6H4 3ab 79 4.5
6 1b 3-Methylthiophen-2-yl 3bb 76 2.5
7 1c 5-Methylthiophen-2-yl 3cb 77 3
8 1a 4-MeSC6H4 3ac 72 4.5
9 1b 3-Methylthiophen-2-yl 3bc 80 2.5
10 1c 5-Methylthiophen-2-yl 3cc 78 2.5
11 12c 1d Thiophen-2-yl 1e  4-NO2C6H4 3dc 3ec 73 55 2 5
aAll products were characterized by 1H NMR, 13C NMR and IR. b Yields after purification by chromatography. c Identified by comparison with authentic sample.38





 http://www.orientjchem.org/wp-content/uploads/2015/10/Vol31_No4_Sur_Elah_Fig1.jpghttp://www.orientjchem.org/wp-content/uploads/2015/10/Vol31_No4_Sur_Elah_Fig2.jpg

I t is a well understood phenomenon that the lower values of the 1H NMR coupling constants of the carbinol protons than 1 Hz, for example 3cc, along with very weak correlation between the 1-H and 2-H (Figure 1) in the NOESY spectrum clearly indicate the relative stereochemistry of the aldol adduct in favor of the syn geometry. Also, in the IR spectrum of 3cc, the broad band of OH was observed with a maximum at 3500 cm-1, which indicates the existence of hydrogen bonding of aldol adduct (Figure 2). In fact, the structure has been fixed in a special stereochemistry which dominated by hydrogen   bonding observed in IR spectra and the tendency to minimize the steric crowding between the 5-Methylthiophen-2-yl and cycloheptanone rings. These results illuminate that 1-C, 2-C, 1-H and 2-H has the same chemical environment, that is to say 3cc is exclusively of syn stereochemistry.


Product (3cc)
Yellow oil; FT-IR (neat) (υmax/cm-1): 1674, 3465. Only syn isomer was isolated. 1H NMR (500 MHz, CDCl3): δH(ppm) 2.92-1.54 (m, 11H), 2.44 (s, 3H), 3.37 (d, J = 3.9 Hz, OH), 5.25 (s, 1H), 6.60 (d, J = 2.4 Hz, 1H), 6.72 (d, J = 3.2 Hz, 1H). 13C NMR (125 MHz, CDCl3): δC(ppm) 15.2, 23.6, 25.3, 28.4, 28.6, 44.0, 57.8, 71.5, 124.5, 124.6, 138.6, 143.3, 217.2. Anal Calcd for C13H18O2S (238): C, 65.54; H, 7.56; S, 13.44. Found: C, 65.53; H, 7.56; S, 13.44.
Oriental Journal of Chemistry
Keshavarz E, Tabatabaeian K, Mamaghani M, Mahmoodi N. O. Surprises in the Study of Ruthenium-catalyzed Stereo- and Chemoselective Aldolizations. Orient J Chem 2015;31(4).


Elahe Keshavarz,1,* Khalil Tabatabaeian2, Manouchehr Mamaghani2 and Nosrat O. Mahmoodi2
1Department of Sciences, Farhangian University, P.O. Box 1998963341, Rasht, Iran.
2Department of Chemistry, Faculty of Sciences, Guilan University, P.O. Box 41335-1914, Rasht, Iran.
Corresponding Author E-Mail: keshavarz@guilan.ac.ir
ABSTRACT: A convenient and diastereoselective method was developed for the synthesis of aldol derivatives in the presence of a catalytic amount of RuCl3.nH2O under solvent-free conditions. Aldol adducts were obtained in good yields and with high chemoselectivity  in short reaction times. In this protocol, aromatic and heteroaromatic aldehydes readily participate as electrophilic cross-aldol partners with a range of cycloalkanones as ketone donors.
KEYWORDS: catalytic aldol reaction; diastereoselective aldolization; green synthesis

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Saturday 21 November 2015

(E)-2-(2-(3-Ethoxy-3-oxoprop-1-enyl)-6-fluorophenyl)acetic acid





(E)-2-(2-(3-Ethoxy-3-oxopropyl-1-enyl)-6-fluorophenyl)acetic acid



.

RM,
 2-fluorophenylacetic acid (1a)
 N-acetyl isoleucine, (3077-46-1)
 ethyl acrylate (2a)(451-82-1)

TLC (hexanes:EtOAc:HOAc, 66:33:1) Rf = 0.29;




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M.p = 97-99 °C;



1H NMR (600 MHz, CDCl3) δ: 1.33 (t, J = 7.2 Hz, 3 H), 3.87 (d, J = 1.8 Hz, 2 H), 4.27 (q, J = 6.6 Hz, 2 H), 6.38 (d, J = 15.6 Hz, 1 H), 7.10 (t, J = 9.6 Hz, 1 H), 7.29 (td, J1 = 8.4, J2 = 6.0 Hz, 1 H), 7.38 (d, J = 7.8 Hz, 1 H), 7.84 (d,J = 15.6 Hz, 1 H);  






predict





13C NMR (150 MHz, CDCl3) δ: 14.2, 30.5 (d, JC-F = 5.1 Hz), 60.9, 116.5 (d, J C-F = 22.7 Hz), 120.5 (d, JC-F = 16.1 Hz), 122.1, 122.5 (d, JC-F = 3.2 Hz), 129.1 (d, JC-F = 9.0 Hz), 136.3 (d, JC-F = 3.5 Hz), 140.3 (d, JC-F = 3.4 Hz), 161.4 (d, JC-F = 245.6 Hz), 166.5, 175.9;



Decoupled 19F NMR (375 MHz, CDCl3) δ: -115.11 (s, 1 F);










v92p0058-5.gif

 IR (film): 2984, 1735, 1705, 1638, 1574, 1462, 1369, 1318, 1264, 1241, 1183, 1156, 1001, 971, 866, 802 cm-1;


HRMS (ESI-TOF) m/z calcd for C13H14FO4 [M+H]+: 253.0876, found: 253.0871;


Anal. calcd. for C13H13FO4: C 61.90, H 5.20, F 7.53, found: C 62.07, H 5.36, F 7.42.




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1-Aminomethyl-cyclobutyl)-acetic acid hydrochloride



EXAMPLE 2
Figure imgf000039_0001
(1) (2)
(iii), (iv)
Figure imgf000039_0002


(l-Aminomethyl-cyclobutyl)-acetic acid hydrochloride
Reagents: (i) Triethylphosphonoacetate, NaH; (ii) MeNO2, Bu4N+F"; (iii) H2, Ni; (iv) HCl
Synthesis of Cyclobutylidene-acetic acid ethyl ester (2)
NaH (60%) dispersion in oil, 1.80 g, 44.94 mmol) was suspended in dry tetrahydrofuran (80 mL) and cooled to 0°C. Triethylphosphonoacetate (9.33 mL, 47.08 mmol) was added and the mixture stirred at 0°C for 15 minutes. Cyclobutanone (1) (3.0 g, 42.8 mmol) in THF (20 mL) was then added and the mixture allowed to warm to room temperature. After 2 hours, the mixture was partitioned between diethyl ether (200 mL) and water (150 mL). The organic phase was separated, washed with brine, dried (MgSO4), and the solvent removed in vacuo at 600 mm Hg. The residue was purified by flash chromatography (silica, ethyl acetate :pentane 1 : 19) to give 5.81 g (96%) of (2) as a colorless oil. iH NMR, 400 MHz (CDCI3): δ 1.27 (3H, t, J=6Hz), 2.09 (2H, m), 2.82 (2H, m),
3.15 (2H, m), 4.14 (2H, q, J = 6 Hz), 5.58 (IH, s).
MS (ES+) m/e: 141 ([MH+], 100%). IR (film) v cm"1: 1088, 1189, 1336, 1673, 1716,2926. Synthesis of (l-Nitromethyl-cyclobutyl)-acetic acid ethyl ester (3)
The unsaturated ester (2) (5.79 g, 41.4 mmol) was dissolved in tetrahydrofuran (20 mL) and stirred at 70°C with nitromethane (4.67 mL, 86.4 mmol) and tetrabutylammonium fluoride (1.0 M in tetrahydrofuran, 55 mL, 55.0 mmol). After 18 hours, the mixture was cooled to room temperature, diluted with ethyl acetate (150 mL), and washed with 2N HCl (60 mL) followed by brine (100 mL). The organic phase was collected, dried (MgSO4), and the solvent removed in vacuo. The residue was purified by flash chromatography (silica, ethyl acetate:heptane 1 :1) to give 4.34 g (52%) of a clear oil. !H NMR 400 MHz (CDC13): δ 1.27 (3H, t, J = 6 Hz), 1.96-2.20 (6H, m), 2.71
(2H, s), 4.15 (2H, q, J = 6 Hz), 4.71 (2H, s).
MS (ES+) m/e: 202 ([MH+], 100%).
IR Cfiln- v cm-1 : 1189, 1378, 1549, 1732, 2984.
Synthesis of (l-Aminomethyl-cyclobutyl)-acetic acid hydrochloride (4) The nitroester (3) (2.095 g, 10.4 mmol) was dissolved in methanol
(50 mL) and shaken over Raney nickel catalyst under an atmosphere of hydrogen (45 psi) at 30°C. After 6 hours, the catalyst was removed by filtration through celite. The solvent was removed in vacuo to give 1.53 g of a pale yellow oil which was used without purification. The oil was dissolved in 1 ,4-dioxane (5 mL) and 6N HCl (15 mL) and heated to reflux. After 5 hours, the mixture was cooled to room temperature, diluted with water (20 mL), and washed with dichloromethane (3 x 30 mL). The aqueous phase was collected and the solvent removed in vacuo. The residue was triturated with ethyl acetate to give 1.35 g (72%) of a white solid after collection and drying. !H NMR 400 MHz (de-DMSO): δ 1.80-2.03 (6H, m), 2.59 (2H, s), 3.02 (2H, s),
8.04 (3H, br s), 12.28 (IH, br s).
MS (ES+) m/e: 144 ([MH-HC1J+, 100%). Microanalysis calculated for C7H14NO2CI:
C, 46.80%; H, 7.86%; N, 7.80%. Found: C, 46.45%; H, 7.98%; N, 7.71%.


Friday 20 November 2015

2nd International conference on Advanced Techniques and Applications of Mass Spectrometry, 19-20 November 2015, Mumbai, India, by SELECTBIO

Advanced Techniques and Applications of Mass Spectrometry


2nd International conference on Advanced Techniques and Applications of Mass Spectrometry, 19-20 November 2015,  at Ramada Powai Hotel and Convention Centre, Mumbai, India, by SELECTBIO
https://selectbiosciences.com/conferences/index.aspx?conf=ATAMS15&se=india 




 A Presentation
PROF SARANJIT SINGH

Saranjit Singh, Professor/Head, NIPER

Dr Saranjit Singh is Professor and Head of the Department of Pharmaceutical Analysis at the National Institute of Pharmaceutical Education and Research (NIPER) at S.A.S. Nagar, Panjab. He acted as Dean of the institute from July 2008-July 2011. He is Member, Expert Advisory Panel on the International Pharmacopoeia and Pharmaceutical Preparations, World Health Organization (WHO), Geneva. He was an invitee member, IARC Monographs Development Program, International Agency for Research on Cancer, Lyon, France in 2013. He also acted as a temporary advisor to WHO Expert Committee on Specifications for Pharmaceutical Preparations between 2007-2010.

Dr Singh is in education and research for the last 32 years. He has published 180 research papers, general articles and book chapters. Till date he has delivered 373 invited lectures at various forums, including AAPS, USP, IPA, IDMA, etc. He is regularly invited to hold full-day training sessions for pharmaceutical industry in India and abroad.

He is a member of Editorial Advisory Board of many journals and reviewer to most of the journals in the area of pharmaceutical analysis.

Dr Singh is recipient of Professor M.L. Khorana Memorial Lecture Award (2005), and IDMA-APA Eminent Analyst (2008) and Outstanding Analyst (2002) Awards.

PROF SARANJIT SINGH





.


With Ashraf mahmoud el marsafy, Dr, Prof., Mr Sanjay Bajaj of selectbio and Anthony Melvin Crasto ,
Bhawna Madan at Ramada Powai Hotel & Convention Centre







 Dr, Prof. Ashraf mahmoud el marsafy, IS LAB DIRECTOR from ministry of agriculture, Egypt




Mrs Zimmer seen in pic holding plate, Anthony Melvin Crasto. AND Mr Markus Zimmer
Mr Markus Zimmer, Head, Analytical Development, Sanofi, in 34184, Montpellier, cedex4, France,  Head of “Chemical and Pharmaceutical Analysis Unit 2”, now responsible for the analytical development of new chemical entities up to clinical phase 2b.



Markus Zimmer in action

Markus Zimmer, Head, Analytical Development, Sanofi

In 1995, Dr Markus Zimmer graduated as licensed pharmacist from the University of Saarland in Saarbrücken/Germany, where he received in 1997 his PhD in Pharmakognosy and Analytical Phytochemistry.
He worked as an Assistant production manager (WALA/Eckwälden) before joining 1999 the Analytical Sciences Department of Hoechst Marrion Roussel (HMR) – now Sanofi - in Frankfurt/Germany as lab head. In parallel, he completed the qualification as pharmacist specialized in Pharmaceutical Technology (2001) and Pharmaceutical Analytics (2003).
In 2006, Markus Zimmer moved to Sanofi in Montpellier/France as Head of “Chemical and Pharmaceutical Analysis Unit 2”, now responsible for the analytical development of new chemical entities up to clinical phase 2b.
Markus Zimmer Image




Anthony Melvin Crasto. with Dr. Juergen Schaefer, Lab Head, Sanofi, Frankfurt



seated Anthony Melvin Crasto. with exactly behind Dr. Juergen Schaefer, Lab Head, Sanofi, Frankfurt
Juergen Schaefer

Juergen Schaefer
Lab Head, Sanofi, Frankfurt

Juergen Schaefer, Lab Head, Sanofi

Dr Juergen Schaefer is currently Laboratory Head for Mass Spectrometry in Analytical Sciences, Lead Generation to Candidate Realization of Sanofi in Frankfurt. He received his Ph.D. in Chemistry from Prof. Michael Karas at Johann Wolfgang Goethe University in Frankfurt (MALDI-TOF-MS) and has about 20 years of experience in Mass Spectrometry of Biopolymers. Since 2000 he worked in Protein Biomarker Discovery using Proteomics Mass spectrometry at Proteome Sciences. He developed Quantitative MS-based Techniques (e.g. TMT, Tandem Mass Tags) for Peptide and Protein Profiling. After joining Sanofi in 2009, he is mainly responsible for Characterization of Peptides and Proteins with Mass Spectrometric Tools in combination with Separation Methods for Analytical Sciences as well as for Characterization of Monoclonal Antibodies for Bioanalytics & Formulation in Frankfurt.

Displaying WP_000426.jpg

Keynote Speakers

Shyamalava Mazumdar
Shyamalava Mazumdar
Senior Professor (I), Tata Institute of Fundamental Research
Juergen Schaefer
Juergen Schaefer
Lab Head, Sanofi
R K Khandal
R K Khandal
President R & D and Business Development, India Glycols Limited
Saranjit Singh
Saranjit Singh
Professor/Head, NIPER
Utpal Tatu
Utpal Tatu
Professor, Indian Institute of Science Bangalore
Alka Beotra
Alka Beotra
Scientific Director & PT Coordinator, National Dope Testing Laboratory
Ravinder Singh
Ravinder Singh
Director, Mayo Clinic
Markus Zimmer
Markus Zimmer
Head, Analytical Development, Sanofi
View all Keynote Speakers

Overview

SELECTBIO is pleased to welcome you to its 2nd Annual Conference on “Advanced Techniques & Applications of Mass Spectrometry” scheduled to be held on November 19-20, 2015 at Ramada Powai Hotel and Convention Centre, Mumbai, India.

After the successful inaugural conference in IICT, Hyderabad last year, this conference has been conceptualized to discuss the advanced techniques and applications of Mass Spectrometry. The experts in this conference will cover various advanced techniques followed by novel applications of Mass Spectrometry in analysis of Pharmaceutical and Forced Degradation products, Metabolites, Food, Environment, Forensic, Clinical and Biological samples. This event will provide you with excellent opportunity to enhance your knowledge on Mass Spectrometry as well as learn the advanced applications in different fields. Further, this event will also help in networking with like minded peers, helping you to build new relationships and optimize your workflow.

Running alongside the conference will be an exhibition covering the latest technological advances and associated services within this field.

Lab Visit

A Mass Spectrometry Lab Visit and Demonstration in SAIF, IIT Bombay will form an integral part of this event.This SAIF Laboratory houses MS Instruments like LC-MS QTOF, GC-MS QTOF, GC- HRMS, ICP- MS, HR- LCMS, LC-MS, TOF-SIMS etc and will cover demonstration of LCMS QTOF & GCMS QTOF.

Who Should Attend

Scientists and Researchers, Biotechnologists, Medical doctors, Clinicians and Chemists from Academics,Pharmaceutical/Biotechnology/Forensic/Food/Environmental Industries, Laboratories working in the following areas/field :

 •Pharmaceutical Analysis, Organic, Analytical & Medicinal Chemistry and Scientists working in Mass Spectrometry and Chromatography Laboratory , Stability Studies, Forced degradation/stress studies in Pharmaceuticals, Formulation Development, Drug Discovery, Biomarker Discovery

•Genomics, Proteomics, Metabolomics & Lipidomics

•Mass Spectrometry for Clinical Diagnosis, Forensic Chemistry, Forensic Sciences, Forensic Medicine and Forensic Toxicology

•Analysis of Food, Dairy Products, Beverages including those engaged in detection of Food Packaging contaminants and Mycotoxins in food samples

•Analysis of Waste water contaminants and Air Pollutants like Pesticides, Perfluorinated compounds and Polyphenolic compounds

International Advisory Board Members

Ruth Andrew, Professor & Chair of Pharmaceutical Endocrinology, University of Edinburgh, UK

Gregori Casals, Scientist, Hospital Clínic Barcelona, Spain

Juergen Gross, Head Mass Spectrometry Lab, Heidelberg University, Germany

Conference Package - Includes Registration and two nights accommodation, (Valid up to November 5, 2015 only)

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Tuesday 17 November 2015

4′-((5-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazol-2-yl-thio)-methyl)-4-fluorobiphenyl-2-carboxamide

str11

Cas 1820758-44-8
C24 H18 F N3 O4 S
4′-((5-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazol-2-yl-thio)-methyl)-4-fluorobiphenyl-2-carboxamide
NMR 1000

NMR 1001
Glycogen synthase kinase-3 (GSK-3) is a constitutively active, ubiquitous serine/threonine kinase that takes part in a number of physiological processes ranging from glycogen metabolism to apoptosis. GSK-3 is a key mediator of various signaling pathways, such as the Wnt and the insulin/AKT signaling pathways.
Therefore, dysregulation of GSK-3 has been linked to various human diseases, such as cancer, diabetes, and neurodegenerative diseases.Two related isoforms of GSK-3 exist in mammals, GSK-3α and -β, which share a sequence identity within their catalytic domains of 98%.
Beyond the catalytic domains they show significant differences. Although these isoforms are structurally related, they are not functionally equivalent, and one cannot compensate for loss of the other.
The debate on the respective contributions of the isoforms GSK-3α and GSK-3β on the pathogenesis of different diseases is ongoing.
Various studies indicate that the therapies of certain diseases benefit from specific targeting of GSK-3α and GSK-3β. GSK-3α was recently identified as a differentiation target in acute myeloid leukemia (AML). AML is a hematopoietic malignancy defined by uncontrolled proliferation and disrupted myeloid differentiation. AML is the second most common form of leukemia in adults.
The current treatment of AML with conventional chemotherapy is very aggressive yet ineffective for the majority of patients with the disease.Thus, alternative targeted treatment approaches for AML are highly desirable. GSK-3α recently emerged as a potential target in this disease.

PAPER


Abstract Image
The challenge for glycogen synthase kinase-3 (GSK-3) inhibitor design lies in achieving high selectivity for one isoform over the other. The therapy of certain diseases, such as acute myeloid leukemia (AML), may require α-isoform specific targeting. The scorpion shaped GSK-3 inhibitors developed by our group achieved the highest GSK-3α selectivity reported so far but suffered from insufficient aqueous solubility. This work presents the solubility-driven optimization of our isoform-selective inhibitors using a scorpion shaped lead. Among 15 novel compounds, compound 27 showed high activity against GSK-3α/β with the highest GSK-3α selectivity reported to date. Compound 27 was profiled for bioavailability and toxicity in a zebrafish embryo phenotype assay. Selective GSK-3α targeting in AML cell lines was achieved with compound 27, resulting in a strong differentiation phenotype and colony formation impairment, confirming the potential of GSK-3α inhibition in AML therapy

Evaluation of Improved Glycogen Synthase Kinase-3α Inhibitors in Models of Acute Myeloid Leukemia

Clemens Schöpf Institute of Organic Chemistry and Biochemistry, Technische Universität Darmstadt, 64287 Darmstadt, Germany
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, United States
J. Med. Chem., Article ASAP
DOI: 10.1021/acs.jmedchem.5b01200
Publication Date (Web): October 23, 2015
Copyright © 2015 American Chemical Society
*Phone: +49 6151 163075. Fax: +49 6151 163278. E-mail: Schmidt_boris@t-online.de.
http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5b01200
http://pubs.acs.org/doi/suppl/10.1021/acs.jmedchem.5b01200/suppl_file/jm5b01200_si_001.pdf
compound 27 as a colorless solid. HPLC: 96%, tR = 6.93 min.
1H NMR (DMSO-d6, 500 MHz, 300 K): δ (ppm) = 4.32 (td, J = 5.2 Hz, J = 3.7 Hz, 4H), 4.60 (s, 2H), 7.05 (d, J = 8.4 Hz, 1H), 7.25 (dd, J = 9.1 Hz, J = 2.7 Hz, 1H), 7.31 (td, J = 8.6 Hz, J = 2.8 Hz, 1H), 7.38 (m, 3H), 7.41 (d, J = 2.0 Hz, 1H), 7.45 (dd, J = 8.4 Hz, J = 2.1 Hz, 1H), 7.49 (d, J = 8.2 Hz, 2H), 7.73 (s, 1H).
13C NMR (DMSO, 125 MHz, 300 K): δ (ppm) = 35.6, 64.1, 64.4, 114.3 (d, JC–F = 21 Hz), 115.0, 115.9 (d, JC–F = 21 Hz), 115.9, 118.1, 120.0, 128.6 (2C), 128.8 (2C), 132.0 (d, JC–F = 8 Hz), 134.8, 135.5, 138.9, 139.0 (d, JC–F = 7 Hz), 143.8, 146.7, 160.9 (d, JC–F = 247 Hz), 162.7, 164.9, 169.5.
EI-MS: m/z = 463 (100, [M+]), 464 (26, [M+ + H]), 465 (7, [M+ + 2H].
ABOUT  Boris Schmidt

Boris Schmidt

Prof. Dr.

RESEARCH EXPERIENCE

  • Mar 2002–present
    Technische Universität Darmstadt · Clemens Schöpf Institut für Organische Chemie und Biochemie
    Germany · Darmstadt
  • May 1999–Feb 2002, Novartis, Novartis Pharma AG
    Switzerland · Basel
  • May 1994–Apr 1999
    Leibniz Universität Hannover · Institute of Organic Chemistry
    Germany · Hannover

AWARDS & ACHIEVEMENTS

  • Nov 2012
    Award: Hans AND Ilse Breuer Award Alzheimer Research
.................................................
ABOUT Theresa Neumann










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Sunday 15 November 2015

Analytical Characterization of new related impurities of Diltiazem, DTZ II (B)




 http://www.orientjchem.org/wp-content/uploads/2015/07/Vol31_No3_Anti_Mana_Fig13.jpg



........

http://www.orientjchem.org/wp-content/uploads/2015/07/Vol31_No3_Anti_Mana_Fig21.jpg.

NOTE DTZ (A) IS DILTIAZEM AND OTHER TWO ARE IMPURITIES


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Structure elucidation of DTZ-II impurity In the positive mass spectra, the protonated [M+H]+ molecular ion was detected at m/z 370.1. The even m/z number of [M+H]+ ions suggest that DTZ-II contains odd number of nitrogen atoms (nitrogen rule). From these results the molecular ion of DTZ-II was found to be at m/z 369. The mass difference between Diltiazem and DTZ-II was found to be 45 amu less. The positive HR-MS spectrum showed protonated molecular ion at m/z 370.1131 corresponding to molecular formula C20H20NO4S. When compared with the molecular formula of Diltiazem, there was a difference of C2H7N. The difference can be rationalized in terms of the loss of trimethyl amine moiety. The presence of additional aromatic signal at δ 7.55 ppm in 1H NMR (Figure 9) and corresponding carbon signal at 131.741 ppm in 13C NMR (Figure 10). The correlation between the carbon and proton clearly observed in HSQC (Figure 11) and one methylene signal was observed in HSQC. The methylene proton at δ 4.38 and 4.71 ppm in 1H NMR corresponding carbon signal at 99.41 ppm in 13C NMR. The aromatic methine proton at δ 7.55 ppm showed HMBC (Figure 12) correlations for carbon C5 and C7 positions at 140.808 and 165.121 ppm respectively (Figure 7). The aromatic methine proton at δ 7.55 ppm showed correlation with methylene proton at δ 4.38 and 4.71 ppm in COSY (Figure 13). NMR assignments are shown in Table 1. The above spectral data supports the assigned structure as 2-(4-methoxyphenyl)-4-oxo-5-vinyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-3-yl acetate (DTZ-II).

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FOLLOW OTHERS IN .........http://www.orientjchem.org/vol31no3/analytical-characterization-of-two-new-related-impurities-of-diltiazem-by-high-resolution-mass-spectrometry-and-nmr-techniques/

Analytical Characterization of two new related impurities of Diltiazem by High Resolution Mass spectrometry and NMR techniques096

Jagadeesh Narkedimilli1,2,*, Y. Ravindrakumar1 ,Sandeep Mohanty1, T. Srinivasarao1, A. Jayashree2
1Dr. Reddy’s Laboratories Limited, API Plant-III, Medak District, Hyderabad 500072, Telangana, India.   2Centre for chemical sciences & Technology, Institute of Science and Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad 500085, Telangana, India.   Corresponding author E-mail: jagadeeshn@drreddys.com
DOI : http://dx.doi.org/10.13005/ojc/310363
ABSTRACT: Diltiazem (DTZ) is an optically active calcium channel blocker having a benzodiazepine structure. Two impurities (referred as DTZ-I and DTZ-II) were detected with area percentages ranging from 0.1% to 0.15% during the impurity profile study of Diltiazem hydrochloride drug substance. A simple isocratic high performance liquid chromatographic method (HPLC) and liquid chromatography–mass spectrometry (LC–MS) were used for the detection. The impurities were isolated by preparative column chromatography. Analytical information from nuclear magnetic resonance and mass spectral data of the potential impurities revealed their structures as 2-(4-methoxyphenyl)-5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-3-yl acetate (DTZ-I) and 2-(4-methoxyphenyl)-4-oxo-5-vinyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-3-yl acetate (DTZ-II). Impurity identification, isolation and structure elucidation were discussed.
KEYWORDS: Diltiazem; Potential impurities; Isolation; characterization techniques

Copy the following to cite this article:

Jagadeesh N, Ravindrakumar Y, Mohanty S, Srinivasarao T, Jayashree A. Analytical Characterization of two new related impurities of Diltiazem by High Resolution Mass spectrometry and NMR techniques. Orient J Chem 2015;31(3).

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DILTIAZEM IS

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