AUTHOR OF THIS BLOG

DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER

KemInnTek Laboratories, helps you synthesize in mg to multi-kg scale.

 regulatory, SYNTHESIS, Uncategorized  Comments Off on KemInnTek Laboratories, helps you synthesize in mg to multi-kg scale.
May 122017
 

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KemInnTek Laboratories

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Welcome to Keminntek Laboratories

Keminntek Laboratories is a Hyderabad (India) based Contract Research Organization in Pharmaceutical sector in specific Pharmaceutical Intermediates, Speciality Chemicals, Impurities and Active Pharmaceutical Ingredients. Promoters of Keminntek Laboratories are Young and Dynamic Technocrats and established with a vision to provide a best-in class pharmaceutical services. Keminntek Laboratories would be a value-added and innovative-in –approach business partner. It has a strong talent pool of qualified and experienced scientists drawn from the national and international institutes and industry. It has a capability to synthesize in mg to multi-kg scale.

About Us

Vision
Our vision is to build Keminntek Laboratories into a world class leading pharmaceutical service provider based on innovation while keeping health and prosperity in mind. Imperatively, we will continue our business with high standards of ethics in the interest of society and environment.Mission
We are committed towards improving people’s health through science and innovation. Our mission is to provide better access of the affordable medicines to the patients and positively impact prosperity.

Team

  • Promoters of this company are very well qualified and experienced personalities in Pharmaceutical sector

  • We have a team consisting

    • Ph.Ds from premier Indian Institutes and postdocs from abroad

    • M. Sc (Chemistry) with 2-12 years pharmaceutical industry experience

  • Our team expertise lies in process R&D of pharmaceutical intermediates, NCEs (Medicinal Chemistry) development, pharmaceutical impurities, and custom synthesis of specialty chemicals

http://keminnteklabs.com/

keminnteklabs@gmail.com

 

Kolupula Srinivas

Kolupula Srinivas

Co-Founder & Chief Scientific Officer at Keminntek Laboratories

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Plot No: 10/11, Road No: 5,
IDA Nacharam, Hyderabad,
India – 500076.
 +91 9515 053 169 / 68
 keminnteklabs@gmail.com
 keminnteklabs@gmail.com

 

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//////////////KemInnTek Laboratories, srinivas kolupula, hyderabad, blog, cro, custom, synthesis

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Dr. Vinayak Pagar( GUEST BLOGGER) Development of a Povarov Reaction/Carbene Generation Sequence for Alkenyldiazocarbonyl Compounds

 cancer, new drugs, spectroscopy, SYNTHESIS  Comments Off on Dr. Vinayak Pagar( GUEST BLOGGER) Development of a Povarov Reaction/Carbene Generation Sequence for Alkenyldiazocarbonyl Compounds
Apr 282017
 

Discussing my paper……..

Metal-catalyzed cycloadditions of alkenyldiazo reagents are useful tools to access carbo- and heterocycles.[1] These diazo compounds are chemically sensitive toward both Brønsted orLewis acids. Their reported cycloadditions rely heavily on the formation of metal carbenes to initiate regio- and stereoselective [3+n] cycloadditions (n=2–4) with suitable dipolarophiles.[2–4] A noncarbene route was postulated for a few copper-catalyzed cycloadditions of these diazo species, but they resulted in complete diazo decomposition.[3a, 4a, 5] oyle and co-workers reported[4a] a [3+2] cycloaddition of the alkenylrhodium carbene A with imines to give dihydropyrroles (Scheme 1a). We proposed a cycloaddition the tetrahydroquinoline derivatives 3 and 3’, as well as the tetrahydro-1H-benzo[b]azepine species 4. Access to these frameworks are valuable

Access to these frameworks are valuable for the preparation of several bioactive molecules including 2-phenyl-2,3-
dihydroquinolone,[8a] L-689,560,[8b] torcetrapib,[8c] martinellic acid,[8d] OPC-31260,[8e] OPC-51803,[8f] and tetraperalone A (Figure 1).[8g] Their specific biological functions have been well documented.[8]

str2

Spectral data for ethyl 2-diazo-2-(2-phenyl-1,2,3,4-tetrahydroquinolin-4-yl) acetate (2a)

Yellow Semi-Solid;

IR (KBr, cm-1 ): 3542 (m), 2117 (s), 3015 (s), 1737 (s), 1564 (s), 1334 (m), 1137 (s), 817 (s);

1H NMR (600 MHz, CDCl3): δ 7.41 (d, J = 7.3 Hz, 2 H), 7.36 ~ 7.33 (m, 2 H), 7.30 (t, J = 7.3 Hz, 2 H), 7.07 (d, J = 7.6 Hz, 1 H), 7.04 (t, J = 7.6 Hz, 1H), 6.71 (t, J = 7.2 Hz, 1H), 6.55 (d, J = 7.9 Hz, 1H) 4.56 (dd, J = 11.0, 2.3 Hz, 1H ), 4.25 (q, J = 7.1 Hz, 2H ), 4.21 (dd, J = 11.0, 5.3 Hz, 1H ), 4.01 (s, 1H) 2.36 ~ 2.33 (m, 1H), 2.00 (dd, J = 11.8, 2.3 Hz, 1H ), 1.28 (t, J = 7.1 Hz, 3H);

13C NMR (150 MHz, CDCl3): δ 167.2, 145.3, 142.9, 128.6, 128.0, 127.8, 126.5, 126.4, 118.8, 117.9, 114.4, 60.9, 59.5, 56.2, 36.8, 32.6, 14.4.

HRMS calcd for C19H19N3O2: 321.1477; found: 321.1483.

Development of a Povarov Reaction/Carbene Generation Sequence for Alkenyldiazocarbonyl Compounds

Authors, Appaso Mahadev Jadhav, Vinayak Vishnu Pagar, and Rai-Shung Liu*, DOI: 10.1002/anie.201205692

 We thank the National Science Council, Taiwan, for financial support of this work., [*] A. M. Jadhav, V. V. Pagar, Prof. Dr. R.-S. Liu

Department of Chemistry, National Tsing Hua University
Hsinchu (30013) (Taiwan)
E-mail: rsliu@mx.nthu.edu.tw

Abstract

original image

Rings aplenty: A HOTf-catalyzed (Tf=trifluoromethanesulfonyl) Povarov reaction of alkenyldiazo species has been developed and delivers diazo-containing cycloadducts stereoselectively (see scheme). The resulting cycloadducts provide access to six- and seven-membered azacycles through the generation of metal carbenes as well as the functionalization of diazo group.

[1] Selected reviews: a) M. P. Doyle,M. A. McKervy, T. Ye, Modern Catalytic Methods for Organic Synthesis with Diazo Compounds,  Wiley, New York, 1998; b) A. Padwa, M. D. Weingarten, Chem. Rev. 1996, 96, 223; c) H. M. L. Davies, J. R. Denton, Chem. Soc. Rev. 2009, 38, 3061; d) M. P. Doyle, R. Duffy, M. Ratnikov, L. Zhou, Chem. Rev. 2010, 110, 704; e) H. M. L. Davies, D. Morton, Chem. Soc. Rev. 2011, 40, 1857; f) Z. Zhang, J. Wang, Tetrahedron
2008, 64, 6577.
[2] Selected examples for carbocyclic cycloadducts, see: a) L. Deng, A. J. Giessert, O. O. Gerlitz, X. Dai, S. T. Diver, H. M. L. Davies, J. Am. Chem. Soc. 2005, 127, 1342; b) H. M. L. Davies, Adv. Cycloaddit. 1999, 5, 119; c) H. M. L. Davies, B. Xing, N. Kong, D. G. Stafford, J. Am. Chem. Soc. 2001, 123, 7461; d) H. M. L. Davies, T. J. Clark, H. D. Smith, J. Org. Chem. 1991, 56, 3819; e) Y. Liu, K. Bakshi, P. Zavalij, M. P. Doyle, Org. Lett. 2010, 12, 4304; f) J. P. Olson, H. M. L. Davies, Org. Lett. 2008, 10, 573.
[3] For oxacyclic cycloadducts, see: a) X. Xu, W.-H. Hu, P. Y. Zavalij, M. P. Doyle, Angew. Chem. 2011, 123, 11348; Angew. Chem. Int. Ed. 2011, 50, 11152; b) M. P. Doyle, W. Hu, D. J. Timmons, Org. Lett. 2001, 3, 3741.

[4] For azacyclic cycloadducts, see selected reviews: a) M. P. Doyle, M. Yan, W. Hu, L. Gronenberg, J. Am. Chem. Soc. 2003, 125, 4692; b) J. Barluenga, G. Lonzi, L. Riesgo, L. A. Lpez, M. Tomas, J. Am. Chem. Soc. 2010, 132, 13200; c) M. Yan, N. Jacobsen, W. Hu, L. S. Gronenberg, M. P. Doyle, J. T. Colyer, D. Bykowski, Angew. Chem. 2004, 116, 6881; Angew. Chem. Int. Ed. 2004, 43, 6713; d) X.Wang, X. Xu, P. Zavalij, M. P. Doyle, J. Am.
Chem. Soc. 2011, 133, 16402; e) Y. Lian, H. M. L. Davies, J. Am. Chem. Soc. 2010, 132, 440; f) X. Xu, M. O. Ratnikov, P. Y. Zavalij, M. P. Doyle, Org. Lett. 2011, 13, 6122; g) V. V. Pagar, A. M. Jadhav, R.-S. Liu, J. Am. Chem. Soc. 2011, 133, 20728; h) R. P. Reddy, H. M. L. Davies, J. Am. Chem. Soc. 2007, 129, 10312.

[5] Y. Qian, X. Xu, X.Wang, P. Zavalij,W. Hu, M. P. Doyle, Angew. Chem. 2012, 124, 6002; Angew. Chem. Int. Ed. 2012, 51, 5900.
[6] Povarov reactions refer to the formal [4+2] cycloadditions of Naryl imines with enol ethers or enamines. See reviews: a) L. S. Povarov, Russ. Chem. Rev. 1967, 36, 656; b) V. V. Kouznetsov, Tetrahedron 2009, 65, 2721; c) D. Bello, R. Ramn, R. Lavilla, Curr. Org. Chem. 2010, 14, 332; d) M. A. McCarrick, Y. D. Wu, K. N. Houk, J. Org. Chem. 1993, 58, 3330; e) A. Whiting, C. M. Windsor, Tetrahedron 1998, 54, 6035.

[7] For Povarov reactions catalyzed by Brønsted acids, see selected examples: a) H. Xu, S. J. Zuend, M. G. Woll, Y. Tao, E. N. Jacobson, Science 2010, 327, 986; b) T. Akiyama, H. Morita, K. Fuchibe, J. Am. Chem. Soc. 2006, 128, 13070; c) H. Liu, G. Dagousset, G. Masson, P. Retailleau, J. Zhu, J. Am. Chem. Soc. 2009, 131, 4598; d) G. Dagousset, J. Zhu, G. Masson, J. Am. Chem. Soc. 2011, 133, 14804; e) H. Ishitani, S. Kobayashi, Tetrahedron Lett. 1996, 37, 7357; f) G. Bergonzini, L. Gramigna, A. Mazzanti, M. Fochi, L. Bernardi, A. Ricci, Chem. Commun.
2010, 46, 327; g) L. He, M. Bekkaye, P. Retailleau, G. Masson, Org. Lett. 2012, 14, 3158.

[8] a) Y. Xia, Z.-Y. Yang, P. Xia, K. F. Bastow, Y. Tachibana, S.-C. Kuo, E. Hamel, T. Hackl, K.-H. Lee, J. Med. Chem. 1998, 41, 1155; b) R.W. Carling, P. D. Leeson, A. M. Moseley, J. D. Smith, K. Saywell, M. D. Trickelbank, J. A. Kemp, G. R. Marshall, A. C. Foster, S. Grimwood, Bioorg. Med. Chem. Lett. 1993, 3, 65;
c) D. B. Damon, R. W. Dugger, R.W. Scott, U.S. Patent 6,689,897, 2004; d) D. A. Powell, R. A. Batey, Org. Lett. 2002, 4, 2913; e) A. Matsuhisa, K. Kikuchi, K. Sakamoto, T. Yatsu, A. Tanaka, Chem. Pharm. Bull. 1999, 47, 329; f) M. Y. Christopher, E. A. Christine, D. M. Ashworth, J. Barnett, A. J. Baxter, J. D. Broadbridge, R. J. Franklin, S. L. Hampton, P. Hudson, J. A. Horton, P. D. Jenkins, A. M. Penson, G. R.W. Pitt, P. Rivire,
P. A. Robson, D. P. Rooker, G. Semple, A. Sheppard, R. M.Haigh, M. B. Roe, J. Med. Chem. 2008, 51, 8124; g) C. Li, X. Li, R. Hong, Org. Lett. 2009, 11, 4036.

About author( Me)

Dr. Vinayak Pagar

Dr. Vinayak Pagar

Postdoctoral Research Fellow at The Ohio State University

Vinayak Vishnu Pagar was born in Nasik, Maharashtra (India) in 1983. He obtained his BSc and MSc degrees in chemistry from the University of Pune (India) in 2004 and 2006, respectively. From 2006–2010, he worked as Research Associate in pharmaceutical companies like Jubilant Chemsys Ltd. and Ranbaxy Laboratories Ltd. (India). In 2010, he joined the group of Professor Rai-Shung Liu to pursue his PhD degree in National Tsing Hua University (Taiwan) and completed it in 2014. Subsequently, he worked as a postdoctoral fellow in the same group for one year. Currently, he is working as a Research Scientist at The Ohio State University, Columbus, Ohio USA. His research focused on the development of new organic reactions by using transition-metal catalysis such Gold, Silver, Rhodium, Zinc, Cobalt, Nickel and Copper metals which enables mild, diastereoselective, enantioselective and efficient transformations of variety of readily available substrates to wide range of synthetically useful nitrogen and oxygen containing heterocyclic products which are medicinally important. He published his research in a very high impact factor international Journals includes  J. Am. Chem. Soc.,  Angew. Chem. Int. Ed.,  J. Org. Chem.,  Chem- A. Eur. Journal,  Org. Biomol. Chem., and Synform (Literature Coverage).

Dr. Vinayak Pagar

Postdoctoral Researcher

Department of Chemistry and Biochemistry

The Ohio State University

100 West 18th Avenue

Columbus, Ohio 43210 USA

vinayak.pagar@gmail.com

/////////Vinayak Pagar, Postdoctoral Research Fellow, The Ohio State University, blog, Povarov Reaction, Carbene Generation Sequence,  Alkenyldiazocarbonyl Compounds

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Towards nitrile-substituted cyclopropanes – a slow-release protocol for safe and scalable applications of diazo acetonitrile

 spectroscopy, SYNTHESIS  Comments Off on Towards nitrile-substituted cyclopropanes – a slow-release protocol for safe and scalable applications of diazo acetonitrile
Apr 222017
 

Towards nitrile-substituted cyclopropanes – a slow-release protocol for safe and scalable applications of diazo acetonitrile

 Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC00602K, Communication
Katharina J. Hock, Robin Spitzner, Rene M. Koenigs
Applications of diazo acetonitrile in cyclopropa(e)nation reactions are realized in a slow-release protocol with bench-stable reagents. Cyclopropyl nitriles are obtained in one step in good diastereoselectivity on a gram-scale providing an efficient entry into this class of fragrances and drug-like molecules.
STR1
STR2
trans-2-phenylcyclopropane-1-carbonitrile
colorless solid (46 mg, 81%);
m.p. = 29°C;
1 H-NMR (600 MHz, CDCl3): δ = 7.34 – 7.30 (m, 2H), 7.28 – 7.24 (m, 1H), 7.12 – 7.08 (m, 2H), 2.63 (ddd, J = 9.2, 6.7, 4.7 Hz, 1H), 1.62 (dt, J = 9.2, 5.4 Hz, 1H), 1.55 (ddd, J = 8.7, 5.5, 4.8 Hz, 1H), 1.45 (ddd, J = 8.8, 6.7, 5.3 Hz, 1H);
13C-NMR (151 MHz, CDCl3): δ = 137.55, 128.76, 127.41, 126.31, 121.05, 24.90, 15.24, 6.63;
HRMS (ESI): m/z calc. for [C10H9NNa]: 166.06272, found 166.06276;
IR (KBr): νmax/cm-1 = 3044, 2235, 2098, 1761, 1600, 1461, 1220, 1051, 920, 705.
The analytical data is in correspondence with the literature [2]
STR1 STR2
[2] M. Gao, N. N. Patwardhan, P. R. Carlier, J. Am. Chem. Soc., 2013, 135 (38), 14390–14400

Towards nitrile-substituted cyclopropanes – a slow-release protocol for safe and scalable applications of diazo acetonitrile

Author affiliations

Abstract

Diazo acetonitrile has long been neglected despite its high value in organic synthesis due to a high risk of explosions. Herein, we report our efforts towards the transient and safe generation of this diazo compound, its applications in iron catalyzed cyclopropanation and cyclopropenation reactions and the gram-scale synthesis of cyclopropyl nitriles.

Graphical abstract: Towards nitrile-substituted cyclopropanes – a slow-release protocol for safe and scalable applications of diazo acetonitrile
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2,2′-(1-(tert-Butoxycarbonyl)pyrrolidine-3,4-diyl)diacetic Acid

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on 2,2′-(1-(tert-Butoxycarbonyl)pyrrolidine-3,4-diyl)diacetic Acid
Feb 012017
 

 

STR1

2,2′-(1-(tert-Butoxycarbonyl)pyrrolidine-3,4-diyl)diacetic Acid

STR1 STR2 STR3 str4 str5

2,2′-(1-(tert-Butoxycarbonyl)pyrrolidine-3,4-diyl)diacetic Acid 

as a white solid. Mp: 162–163 °C, % purity: 94.09% (HPLC);
1H NMR (DMSO-d6, 400 MHz) δ: 1.38 (s, 9H), 2.10–2.18 (m, 2H), 2.28–2.32 (m, 2H), 2.49–2.50 (m, 2H, merged with DMSO peak), 2.97–3.03 (m, 2H), 3.33–3.40 (m, 2H), 12.23 (bs, 2H); 1H NMR (CD3OD, 400 MHz) δ: 1.46 (s, 9H), 2.26 (ddd, J1 = 2.8 Hz, J2 = 9.2 Hz, J3 = 16.0 Hz, 2H), 2.43 (dd, J1 = 5.2 Hz, J2 = 16.0 Hz, 2H), 2.69 (m, 2H), 3.16 (dd, J1 = 5.2 Hz, J2 = 10.8 Hz, 2H), 3.49–3.54 (m, 2H);
13C NMR (DMSO-d6, 100 MHz) δ: 28.49, 32.97, 36.49, 37.31, 50.10, 50.20, 78.67, 154.05, 173.96;
IR (KBr): ν = 871, 933, 1143, 1166, 1292, 1411, 1689, 1708, 2881, 2929, 2980, 3001 cm–1;
TOFMS: [C13H21NO6 – H+]: calculated 286.1296, found 286.1031(100%).
HPLC conditions were as follows for compound ; Agilent 1100 series, column: YMC J’SPHERE C18 (150 mm X 4.6 mm) 4µm with mobile phases A (0.05% TFA in water) and B (acetonitrile). Detection was at 210 nm, flow was set at 1.0 mL/min, and the temperature was 30 °C (Run time: 45 min). Gradient: 0 min, A = 90%, B = 10%; 5.0 min, A = 90%, B = 10%; 25 min, A = 0%, B = 100%; 30 min, A = 0%, B = 100%, 35 min, A = 90%, B = 10%; 45 min, A = 90%, B = 10%.
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.6b00399
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Dimethyl 4,4′-(Benzylazanediyl)(2E,2′E)-bis(but-2-enoate)

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on Dimethyl 4,4′-(Benzylazanediyl)(2E,2′E)-bis(but-2-enoate)
Jan 312017
 

str5

Dimethyl 4,4′-(Benzylazanediyl)(2E,2′E)-bis(but-2-enoate)

STR1

IR (CHCl3): ν = 758, 1215, 1278, 1437, 1660, 1720, 2806, 2953, 3020, 3421 cm–1;

 

STR2

13C NMR (CDCl3, 100 MHz) δ: 51.53, 53.42, 58.37, 122.66, 127.28, 128.41, 128.55, 128.76, 138.24, 145.84, 166.58;

 

STR3

1H NMR (CDCl3, 400 MHz) δ: 3.23 (dd, J1 = 1.6 Hz, J2 = 6.0 Hz, 4H), 3.62 (s, 2H), 3.75 (s, 6H), 6.07 (dt, J1 = 1.6 Hz, J2 = 16.0 Hz, 2H), 6.97 (dt, J1 = 6.0 Hz, J2 = 16.0 Hz, 2H), 7.25–7.34 (m, 5H-merged with CDCl3 proton);

 

str4

TOFMS: [C17H21NO4 + H+]: calculated 304.1543, found 304.1703(100%).

str5

 

UPLC conditions were as follows for compound 11; Acquity Waters, column: BEH C18 (2.1 mm X 100 mm) 1.7 µm with mobile phases A (0.05% TFA in water) and B (acetonitrile). Detection was at 220 nm, flow was set at 0.4 mL/min, and the temperature was 30 °C (Run time: 9 min). Gradient: 0 min, A = 90%, B = 10%; 0.5 min, A = 90%, B = 10%; 6.0 min, A = 0%, B = 100%; 7.5 min, A = 0%, B = 100%; 7.6 min, A = 90%, B = 10%; 9.0 min, A = 90%, B = 10%.

 

Dimethyl 4,4′-(Benzylazanediyl)(2E,2′E)-bis(but-2-enoate) (11)

as a yellow oil. % purity: 93.4% (UPLC);
1H NMR (CDCl3, 400 MHz) δ: 3.23 (dd, J1 = 1.6 Hz, J2 = 6.0 Hz, 4H), 3.62 (s, 2H), 3.75 (s, 6H), 6.07 (dt, J1 = 1.6 Hz, J2 = 16.0 Hz, 2H), 6.97 (dt, J1 = 6.0 Hz, J2 = 16.0 Hz, 2H), 7.25–7.34 (m, 5H-merged with CDCl3 proton);
13C NMR (CDCl3, 100 MHz) δ: 51.53, 53.42, 58.37, 122.66, 127.28, 128.41, 128.55, 128.76, 138.24, 145.84, 166.58;
IR (CHCl3): ν = 758, 1215, 1278, 1437, 1660, 1720, 2806, 2953, 3020, 3421 cm–1;
TOFMS: [C17H21NO4 + H+]: calculated 304.1543, found 304.1703(100%).
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.6b00399
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One-Pot Reductive Cyclisations of Nitroanilines to Imidazoles

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on One-Pot Reductive Cyclisations of Nitroanilines to Imidazoles
Jan 252017
 

Hana and co-workers ( Synlett 2010, 18, 2759−2764) from Genentech have developed a single-step procedure for conversion of 2-nitro aromatic amines to benzimidazoles. Addition of ammonium chloride proved necessary as Fe powder and formic acid alone was ineffective for nitro reduction. These conditions were compatible with a variety of functional groups on the aromatic, including boronate esters. The methodology was also extended to nitro aminopyridines but failed to deliver the desired product with isoxazole or pyrazole reactants.

Mild and General One-Pot Reduction and Cyclization of Aromatic and Heteroaromatic 2-Nitroamines to Bicyclic 2H-Imidazoles

Emily J. Hanan*, Bryan K. Chan, Anthony A. Estrada, Daniel G. Shore, Joseph P. Lyssikatos

*Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA, Email: hanan.emilygene.com

E. J. Hanan, B. K. Chan, A. A. Estrada, D. G. Shore, J. P. Lyssikatos, Synlett, 2010, 2759-2764.

DOI: 10.1055/s-0030-1259007


see article for more reactions

Abstract

A one-pot procedure for the conversion of aromatic and heteroaromatic 2-nitroamines into bicyclic 2H-benzimidazoles employs formic acid, iron powder, and NH4Cl as additive to reduce the nitro group and effect the imidazole cyclization with high-yielding conversions generally within one to two hours. The compatibility with a wide range of functional groups demonstrates the general utility of this procedure.


see article for more examples

//////////One-Pot, Reductive Cyclisations,  Nitroanilines,  Imidazoles

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This article is a compilation for educational purposes only.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

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A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles: an easy access to five-ring-fused tetrahydroisoquinolines

 PROCESS, spectroscopy, SYNTHESIS  Comments Off on A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles: an easy access to five-ring-fused tetrahydroisoquinolines
Jan 062017
 

Graphical abstract: A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles: an easy access to five-ring-fused tetrahydroisoquinolines

 

We have reported herein a catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles by which a series of five-ring-fused tetrahydroisoquinolines featuring an indoline scaffold were obtained as single diastereomers in moderate to high yields without any additives under mild conditions. Moreover, the current method provides a novel and convenient approach for the efficient incorporation of two biologically important scaffolds (tetrahydroisoquinoline and indoline).

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C6GC02517J?utm_medium=email&utm_campaign=pub-GC-vol-19-issue-1&utm_source=toc-alert#!divAbstract

A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles: an easy access to five-ring-fused tetrahydroisoquinolines

Xihong Liu,a   Dongxu Yang,a   Kezhou Wang,a  Jinlong Zhanga and   Rui Wang*ab  
*Corresponding authors
aSchool of Life Sciences, Institute of Biochemistry and Molecular Biology, Lanzhou University, Lanzhou 730000, P. R. China
E-mail: wangrui@lzu.edu.cn
bState Key Laboratory of Chiroscience, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, P. R. China
E-mail: bcrwang@polyu.edu.hk
Green Chem., 2017,19, 82-87

DOI: 10.1039/C6GC02517J

 

 ethyl 13b-nitro-8-tosyl-8,8a,13b,13c-tetrahydro-5H-indolo[2′,3′:3,4]pyrazolo[5,1- a]isoquinoline-9(6H)-carboxylate: White solid, m.p. 153 – 154 oC; 94% yield;
1H NMR (300 MHz, CDCl3) δ 7.86 (d, J = 8.2 Hz, 2H), 7.78 (d, J = 7.9 Hz, 1H), 7.30 – 7.13 (m, 5H), 7.1 (s, 1H), 7.05 – 6.94 (m, 1H), 6.94 – 6.87 (m, 1H), 6.59 (t, J = 7.6 Hz, 3H), 6.28 (d, J = 7.6 Hz, 1H), 4.78 (s, 1H), 4.37 (q, J = 7.1 Hz, 2H), 2.80 – 2.58 (m, 2H), 2.33 (s, 3H), 2.31 – 2.11 (m, 2H), 1.41 (t, J = 7.1 Hz, 3H) ppm;
13C NMR (75 MHz, CDCl3) δ 152.1, 144.6, 142.6, 134.0, 132.1, 129.3, 129.0, 128.7, 128.3, 127.5, 127.3, 126.2, 122.8, 121.1, 115.5, 104.5, 84.9, 70.7, 62.8, 48.5, 29.1, 21. 6, 14.3 ppm;
HRMS (ESI): C27H26N4NaO6S [M + Na]+ calcd: 557.1465, found: 557.1476.

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This article is a compilation for educational purposes only.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

/////////// catalyst-free,  1,3-dipolar cycloaddition, C,N-cyclic azomethine imines,  3-nitroindoles,  five-ring-fused tetrahydroisoquinolines
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Overcoming barriers to green chemistry in the pharmaceutical industry – the Green Aspiration Level™ concept

 SYNTHESIS, Uncategorized  Comments Off on Overcoming barriers to green chemistry in the pharmaceutical industry – the Green Aspiration Level™ concept
Jan 062017
 

Image result for Frank Roschangar

 

 

Image result for Frank Roschangar

Scheme 1. Pfizer’s Commercial Synthesis of sildenafil citrate (Viagra™)

Image result for Overcoming Barriers to Green Chemistry in the Pharmaceutical Industry - The Green Aspiration Level™ Concept

 

 

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Image result for Frank Roschangar

Image result for Frank Roschangar

“Green chemistry” refers to the promotion of safe, sustainable, and waste-minimizing chemical processes. The proliferation of green chemistry metrics without any clear consensus on industry standards is a significant barrier to the adoption of green chemistry within the pharmaceutical industry. We propose the Green Aspiration Level™ (GAL) concept as a novel process performance metric that quantifies the environmental impact of producing a specific pharmaceutical agent while taking into account the complexity of the ideal synthetic process for producing the target molecule. Application of the GAL metric will make possible for the first time an assessment of relative greenness of a process, in terms of waste, versus industry standards for the production process of any pharmaceutical. Our recommendations also include a simple methodology for defining process starting points, which is an important aspect of standardizing measurement to ensure that Relative Process Greenness (RPG) comparisons are meaningful. We demonstrate our methodology using Pfizer’s Viagra™ process as an example, and outline aspiration level opportunities for industry and government to dismantle green chemistry barriers.

 

Graphical abstract: Overcoming barriers to green chemistry in the pharmaceutical industry – the Green Aspiration Level™ concept

 

Overcoming barriers to green chemistry in the pharmaceutical industry – the Green Aspiration Level™ concept

*Corresponding authors
aChemical Development US, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, USA
E-mail: frank.roschangar@boehringer-ingelheim.com
bDelft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands
Green Chem., 2015,17, 752-768

DOI: 10.1039/C4GC01563K, http://pubs.rsc.org/en/content/articlelanding/2015/gc/c4gc01563k#!divAbstract

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This article is a compilation for educational purposes only.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

///////////green chemistry,  pharmaceutical industry

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One-step asymmetric synthesis of (R)- and (S)-rasagiline by reductive amination applying imine reductases

 spectroscopy, SYNTHESIS  Comments Off on One-step asymmetric synthesis of (R)- and (S)-rasagiline by reductive amination applying imine reductases
Dec 252016
 

Graphical abstract: One-step asymmetric synthesis of (R)- and (S)-rasagiline by reductive amination applying imine reductases

One-step asymmetric synthesis of (R)- and (S)-rasagiline by reductive amination applying imine reductases

Green Chem., 2017, Advance Article
DOI: 10.1039/C6GC03023H, Communication
P. Matzel, M. Gand, M. Hohne
Imine reductases (IREDs) show great potential as catalysts for reductive amination of ketones to produce chiral secondary amines.

One-step asymmetric synthesis of (R)- and (S)-rasagiline by reductive amination applying imine reductases

Imine reductases (IREDs) show great potential as catalysts for reductive amination of ketones to produce chiral secondary amines. In this work, we explored this potential and synthesized the pharmaceutically relevant (R)-rasagiline in high yields (up to 81%) and good enantiomeric excess (up to 90% ee) from the ketone precursor. This one-step approach in aqueous medium represents the shortest synthesis route from achiral starting materials. Furthermore, we demonstrate for the first time that tertiary amines also can be accessed by this route, which provides new opportunities for eco-friendly enzymatic asymmetric syntheses of these important molecules.

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C6GC03023H?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

One-step asymmetric synthesis of (R)- and (S)-rasagiline by reductive amination applying imine reductases

P. Matzel,a   M. Gandb and   M. Höhne*a  
*Corresponding authors
aInstitute of Biochemistry, Greifswald University, Felix-Hausdorff-Str. 4, 17487 Greifswald, Germany
E-mail: Matthias.Hoehne@uni-greifswald.de
bBiocenter Klein Flottbek, University of Hamburg, Ohnhorststr. 18, 22609 Hamburg, Germany
Green Chem., 2017, Advance Article

DOI: 10.1039/C6GC03023H

str0 str1 str2 str3 str4

////////////One-step, asymmetric synthesis,  (R)- ,  (S)-rasagiline,  reductive amination,  imine reductases

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Synthesis of (E)-2,4-Dinitro-N-((2E,4E)-4-phenyl-5-(pyrrolidin-1-yl)penta-2,4-dienylidene)aniline

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on Synthesis of (E)-2,4-Dinitro-N-((2E,4E)-4-phenyl-5-(pyrrolidin-1-yl)penta-2,4-dienylidene)aniline
Dec 212016
 

str1

Cas 1204588-48-6
MF C21 H20 N4 O4
MW 392.41
Benzenamine, 2,​4-​dinitro-​N-​[(2E,​4E)​-​4-​phenyl-​5-​(1-​pyrrolidinyl)​-​2,​4-​pentadien-​1-​ylidene]​-​, [N(E)​]​-
(E)-2,4-Dinitro-N-((2E,4E)-4-phenyl-5-(pyrrolidin-1-yl)penta-2,4-dienylidene)aniline
str1

 

 

Molbank 2009, 2009(3), M604; doi:10.3390/M604

Synthesis of (E)-2,4-Dinitro-N-((2E,4E)-4-phenyl-5-(pyrrolidin-1-yl)penta-2,4-dienylidene)aniline
Nosratollah Mahmoodi 1,*, Manuchehr Mamaghani 1, Ali Ghanadzadeh 2, Majid Arvand 3 and Mostafa Fesanghari 1
1Laboratory of Organic Chemistry, Faculty of Science, University of Guilan, P.O.Box 1914, Rasht, Iran,
2Departments of Physical Chemistry, Faculty of Science, University of Guilan, P.O.Box 1914, Rasht, Iran
3Departments of Analytical Chemistry, Faculty of Science, University of Guilan, P.O.Box 1914, Rasht, Iran
*Author to whom correspondence should be addressed
mahmoodi@guilan.ac.ir, m-chem41@guilan.ac.ir, aggilani@guilan.ac.ir, arvand@guilan.ac.ir, nosmahmoodi@gmail.com

Abstract:

(E)-2,4-Dinitro-N-((2E,4E)-4-phenyl-5-(pyrrolidin-1-yl)penta-2,4-dienylidene) aniline dye was prepared in one pot by reaction of premade N-2,4-dinitrophenyl-3-phenylpyridinium chloride (DNPPC) and pyrrolidine in absolute MeOH.
Keywords:

N-2,4-dinitrophenyl-3-phenylpyridinium chloride (DNPPC); photochromic; pyridinium salt

N-2,4-Dinitrophenyl-3-phenylpyridinium chloride (DNPPC) 1 was prepared according to the literature method [1,2,3,4,5,6,7]. Recently, we became interested in the synthesis of photochromic compounds [8,9,10]. The UV-Vis spectra under irradiation of UV light of dye 2 indicate photochromic properties for this molecule. The salt 1 was premade and typically isolated and purified by recrystallization and characterized. To a solution of 1-chloro-2,4-dinitrobenzene (1.42 g, 7.01 mmol) in acetone (10 mL) was added 3-phenylpyridine (1.0 mL, 6.97 mmol). The reaction was heated at reflux for 48 h. The solvent was removed under reduced pressure and the red residue was stirred in hexanes. The precipitated product was collected by vacuum filtration to afford pure pyridinium salt 1 as a reddish brown solid (2.23 g, 6.25 mmol, 90%). 1H NMR (CDCl3, 500 MHz): δ (ppm) 9.9 (s, 1H), 9.4 (d, J = 6.0 Hz, 1H), 9.3 (d, J = 8.3 Hz, 1H), 9.2 (d, J = 2.2 Hz, 1H), 9.0 (dd, J = 8.7, 2.4 Hz, 1H), 8.5-8.6 (m, 2H), 8.0 (d, J = 7.3 Hz, 2H), 7.6- 7.7 (m, 3H); 13C NMR (CDCl3, 125 MHz): δ (ppm) 149.2, 145.6, 144.3, 144.2, 143.0, 139.2, 138.7, 132.5, 132.3, 130.6, 130.2, 129.6, 128.0, 127.6, 121.3; IR (KBr pellet) 3202, 3129, 2994, 2901, 1609 cm-1; m. p. = 182-183 °C; HRMS m/z Calcd for C17H12N3O4+ (M)+ 322.0828, found 322.0836.
Molbank 2009 m604 i001
Reaction of pyrrolidine with salt (1) leads to the opening of the pyridinium ring and formation of dye 2. This dye was prepared from reaction of salt 1 (0.5 g, 1.4 mmol) in 5 mL absolute MeOH after cooling a reaction mixture to -10oC and keeping at this temperature for 15 min. To this was added pyrrolidine (0.1 g, 1.4 mmol) in 3 mL absolute MeOH over a period of 10 min. The prepared solid was filtered, washed with CH2Cl2, dried and recrystallized from n-hexane to yield 68% (0.37 g, 0.95 mmol) of pure metallic greenish-brown 2,
m.p. = 146 oC.
IR (KBr): 3040, 2950, 1616, 1514, 1492, 1469, 1321, 1215, 1170, 1105, 956, 904, 862, 727 cm-1.
1H NMR (500 MHz, CDCl3): δ (ppm) 8.7 (d, J = 2.4 Hz, 1H) 8.3 (dd, J = 2.4, 8.84 Hz, 1H), 8.0 (s, 1H), 7.5 (d, J = 7.4 Hz, 2H), 7.4-7.5 (t, J = 7.5 Hz, 2H), 7.3-7.4 (m, 1H), 7.2 (d, J = 12.5 Hz, 1H), 7.1 (d, J = 8.9 Hz, 1H), 7.0 (d, J = 12.1 Hz, 1H), 5.4 (t, J = 12.2 Hz, 1H), 3.3 (br, 4H), 2.0 (br, 4H);
13C NMR (125 MHz, CDCl3): δ (ppm) 22.0, 55.6, 114.7, 117.4, 120.0, 124.1, 126.4, 128.7, 128,8, 129.0, 132.7, 137.1, 137.3, 142.9, 147.8, 150.2, 163.8.
Anal. Calcd for C21H20N4O4: %C = 64.28, %H = 5.14, %N = 14.28. Found: %C = 64.08, %H = 5.11, %N = 14.07.

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1H NMR PREDICT

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ACTUAL….

1H NMR (500 MHz, CDCl3): δ (ppm) 8.7 (d, J = 2.4 Hz, 1H) 8.3 (dd, J = 2.4, 8.84 Hz, 1H), 8.0 (s, 1H), 7.5 (d, J = 7.4 Hz, 2H), 7.4-7.5 (t, J = 7.5 Hz, 2H), 7.3-7.4 (m, 1H), 7.2 (d, J = 12.5 Hz, 1H), 7.1 (d, J = 8.9 Hz, 1H), 7.0 (d, J = 12.1 Hz, 1H), 5.4 (t, J = 12.2 Hz, 1H), 3.3 (br, 4H), 2.0 (br, 4H);

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13 C NMR PREDICT

 

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ACTUAL…….13C NMR (125 MHz, CDCl3): δ (ppm) 22.0, 55.6, 114.7, 117.4, 120.0, 124.1, 126.4, 128.7, 128,8, 129.0, 132.7, 137.1, 137.3, 142.9, 147.8, 150.2, 163.8.

str3

////////////Synthesis, (E)-2,4-Dinitro-N-((2E,4E)-4-phenyl-5-(pyrrolidin-1-yl)penta-2,4-dienylidene)aniline

[O-][N+](=O)c3ccc(\N=C\C=C\C(=C/N1CCCC1)c2ccccc2)c([N+]([O-])=O)c3

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