Bromoclenbuterol

Bromoclenbuterol

Bromoclenbuterol; CAS 37153-52-9; Chlorbrombuterol; AC1MC7W8;
Molecular Formula:	C12H18BrClN2O
Molecular Weight:	321.64112 g/mol

CLIP

http://dx.doi.org/10.1016/j.chroma.2012.08.031

Journal of Chromatography A

Volume 1258, 5 October 2012, Pages 55–65

 

Wide-range screening of banned veterinary drugs in urine by ultra high liquid chromatography coupled to high-resolution mass spectrometry

• Nuria León^a,
• Marta Roca^a,
• Carmen Igualada^a,
• Claudia P.B. Martins^b,
• Agustín Pastor^c,
• Vicent Yusá^a, ,

• ^a Center for Public Health Research (CSISP), Avda de Cataluña 21, 46020 Valencia, Spain
• ^b Thermo Fisher Scientific, Barcelona, Spain
• ^c Analytical Chemistry Department, Universidad de Valencia, Edifici Jeroni Muñoz, 50, Dr. Moliner, 46100 Burjassot, Valencia, Spain

CLIP

Synthesis and Characterization of Bromoclenbuterol

Ravi Kumar Kannasani^*, Srinivasa Reddy Battula, Suresh Babu Sannithi, Sreenu Mula and Venkata Babu VV

R&D Division, RA Chem Pharma Limited, API, Hyderabad, Telangana, India

*Corresponding Author:

Ravi Kumar Kannasani
R&D Division, RA Chem Pharma Limited
API, Prasanth Nagar, Hyderabad, Telangana, India
Tel: +919000443184
E-mail: kannasani.ravi@rachempharma.com

http://www.omicsonline.org/open-access/synthesis-and-characterization-of-bromoclenbuterol-2161-0444-1000397.php?aid=79341

Citation: Kannasani RK, Battula SR, Sannithi SB, Mula S, Babu VVV (2016) Synthesis and Characterization of Bromoclenbuterol. Med Chem (Los Angeles) 6:546-549. doi:10.4172/2161-0444.1000397

4-Amino acetophenone (1) was reacted with N-Chlorosuccinimide in 1N HCl to afford 4-amino-3-chloro acetophenone (7), which was reacted with bromine to give 1-(4-amino-3-bromo-5-chlorophenyl)- 2-bromoethanone (8). The obtained bromo compound was reacted with tertiay -butyl amine to afford 2-(tert-butylamino)-1-(4-amino-3- bromo-5-chlorophenyl)ethanone (9), which was reduced with sodium borohydride in methanol to give bromoclenbuterol compound (10). The synthesized bromoclenbuterol structure was confirmed by ¹H NMR, ¹³C NMR, IR and mass spectra.

1-(4-Amino-3-chlorophenyl)ethanone (7)

To a stirred solution of 1N HCl (1500 ml) was added 4-amino acetophenone (1) (200 gm, 1.48 mole) and N-Chloro succinimide (50 gm, 0.37 mole) at room temperature, and stirring continued for 3 hrs at 25-30°C. After maintenance undissolved material was filtered from the reaction mixture, total filtrate was taken and extracted with ethyl acetate, dried over sodium sulfate and evaporated under vacuum to get crude. Crude material was dissolve in ethyl acetate, titrated with EA-HCl and stirred for 15-30 min to get precipitation. The obtained precipitate was filtered and washed with ethyl acetate, and this acidic titration operation was repeated 2 times to get mono chloro compound as solid material, this solid material was neutralized with sodium carbonate solution in aqueous condition and further purified by using recrystlliaztion technique in ethyl acetate to get 68 gm (yield-27%) 3-chloro-4-amino acetophenone (7) (mono chloro compound), as light brown colored solid with 98.66% HPLC purity (124 gm of unreacted 4-amino acetophenone obtained from aqueous layer).

1-(4-Amino-3-bromo-5-chlorophenyl)-2-bromoethanone (8)

To a stirred solution of 3-chloro-4-amino acetophenone (7) (14 gm, 0.082 mole) in chloroform (140 ml) was added bromine (26.24 gm, 0.164 mole) solution slowly at 25-30°C and stirring continued for 6 hrs at same temperature. After completion of the reaction, methanol was added to the reaction mixture and continued the stirring for 30 min at RT. Undissolved material was filtered, the filtrate was distilled up to 50%, remaining mass was cooled to 0-5°C and filtered to give 15 gm (yield-55%) of 1-(4-amino -3-chloro-5-bromo - phenyl) -2-bromo ethanone (8) as light brown color solid with 95.15% HPLC purity.

2-(Tert-butylamino)-1-(4-amino-3-bromo-5-chlorophenyl) ethanone (9)

To a stirred solution of 1-(4-amino -3-chloro-5-bromo - phenyl) -2-bromo ethanone (8) (8 gm, 0.024 mole) in chloroform (50 ml) was added catalytic amount of potassium iodide (0.1 gm, 0.0006 mole) and tertiary butyl amine (5.2 gm, 0.072 mole) at 0-5°C and stirring was continued for 24 hrs at 0-5°C. After completion of the reaction, undissolved salts were filtered, the filtrate was distilled under vacuum to get crude solid material, which was triturated with hexane to give 6 gm (yield-76%) of 1-(4-amino-3-chloro-5-bromo phenyl)-2-[(1,1- dimethylethyl)amino]ethanone (9) as light pale yellow color solid.

(S)-2-(Tert-butylamino)-1-(4-amino-3-bromo-5- chlorophenyl)ethanol (10)

To a stirred solution of 1-(4-Amino-3-chloro-5-bromo phenyl)- 2-[(1,1-dimethylethyl)amino]ethanone (9) (6 gm, 0.018 mole) in methanol (25 ml) was added sodium borohydride (0.7 gm, 0.018 mole) at 0-5°C. After addition, reaction mixture was slowly allowed to come to room temperature and stirred for 10 hrs at 25-30°C. On completion, reaction mixture was poured in to chilled water, obtained precipitate was filtered, dried and recrystallized in methanol to give 5 gm (yield-82%) of 1RS-1-(4-amino -3-bromo-5-chloro phenyl) -2-[(1,1-dimethyl ethyl)amino ethanol (or) Bromo clenbuterol (10) as off-white solid. HPLC purity-98.80%,

1H NMR (CDCl₃): δ 7.35 (d, 1H, J=1.2 Hz), 7.23 (d, 1H, J=1.6 Hz), 4.45 (br s, 2H), 4.42 (dd, 1H, J=9.2, 3.6 Hz), 2.84 (dd, 1H, J=11.6, 3.6 Hz), 2.50 (dd, 1H, J=12.0, 9.2 Hz), 1.10 (s, 9H).

¹³C NMR (CDCl₃): 140.12, 133.93, 128.46, 126.05, 119.16, 109.08, 70.94, 50.33, 50.05, 29.15.

IR (KBr, Cm^-1): 3465.99, 3320.19, 2965.04, 1623.40, 1483.88, 1219.17, 758.77, 630.41.

Mass: (m/z)-323.01 (M⁺² peak).

References

1. International Conference on Harmonization (ICH) Guidelines (2002) Q3A (R) Impurities in New Drug Substances.
2. ICH (2006) Impurities in New Drug Products. Q3B (R1).
3. Srinivasulu R, Ravi Kumar K, Nageswararao K (2016) Synthesis of 3,4-dihydropyrimidin-2(1H)-ones using camphor sulfonic acid as a catalyst under solvent-free conditions. Derpharma chemica 8: 375-379.
4. Antuna AZ, Ivan L, Pablo RG, Julio R, Jose, et al. (2011) V. Tetrahedron 67: 5577-5581.
5. Ehrhardt JD (1990) Synthesis of nonadeutero-clenbuterol. Journal of labeled compounds and radiopharmaceuticals 28: 725-729.
6. Drabb TW (1990) Method for the preparation of 4'-(substituted)-amino-2-(substituted) Amino-3’,5'-dichloroacetophenone and salts thereof Trenton. NJ Patent: US4906781A.
7. Bentley TJ (1984) Method for the preparation of 1-(4'-amino-3',5'-dichlorophenyl)-2-alkyl(or dialkyl)aminoethanols. US4461914 A.

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2,3,4,4a,5,6-hexahydro-1H-pyrido[1,2-a]quinolone (R)-7

1H NMR (500 MHz, CDCl3): δ 7.82 (br s, 1H), 7.28-7.34 (m, 2H), 7.22-7.24 (m, 1H), 3.87 (m, 1H), 3.56 (m, 1H), 3.32 (m, 1H), 3.00-3.03 (m, 2H), 2.46-2.74 (m, 3H), 1.65-2.05 (m, 5H);

13C NMR (100 MHz, CDCl3): δ 137.6, 130.4, 129.2, 127.9, 124.1, 55.9, 54.5, 27.3, 25.2, 22.9, 20.3, 17.1;

Enantiomeric excess was determined by SFC: Chiralpak OD-3, 4.6 mm x 150 mm, particle size: 3 μm, temperature: 30 ºC, A: CO2, B: ethanol with 0.2% of isobutylamine, isocratic: A/B: 95/5, v/v, flow rate 3.0 mL/min.

HRMS (ESI) [M+H]+ m/z calcd for [C13H18N]+ is 188.1361 found 188.1429.

Synthesis of Enantioenriched 2‐Alkyl Piperidine Derivatives through
Asymmetric Reduction of Pyridinium Salts
Bo Qu,* Hari P. R. Mangunuru, Xudong Wei, Keith R. Fandrick, Jean-Nicolas Desrosiers, Joshua D.
Sieber, Dmitry Kurouski, Nizar Haddad, Lalith P. Samankumara, Heewon Lee, Jolaine Savoie, Shengli
Ma, Nelu Grinberg, Max Sarvestani, Nathan K. Yee, Jinhua J. Song and Chris H. Senanayake
Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road,
Ridgefield, CT 06877 USA
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N-(4-methylphenyl)-3-exo-(4-methoxybenzyl)tricyclo[3.2.1.02,4]octane-6,7-end o-dicarboximide

N-(4-methylphenyl)-3-exo-(4-methoxybenzyl)tricyclo[3.2.1.02,4]octane-6,7-end o-dicarboximide

petroleum ether/EtOAc (10/1→3/1) to give white solid, 185.8 mg, 96 % yield. Mp: 193-195 oC; 1H NMR (400 MHz, CDCl3) δ 7.28 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.8 Hz, 2H), 7.00 (d, J = 8.0 Hz, 2H), 6.84 (d, J = 8.4 Hz, 2H), 3.81 (s, 3H), 3.21 (s, 2H), 2.99 (s, 2H), 2.46 (d, J = 6.4 Hz, 2H), 2.40 (s, 3H), 1.40 (d, J = 11.2 Hz, 1H), 1.22 (t, J = 6.4 Hz, 1H), 1.07 (d, J = 10.8 Hz, 1H), 0.92 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 177.2, 157.9, 138.7, 132.3, 129.8, 129.4, 129.2, 126.4, 113.6, 55.1, 49.3, 39.0, 35.8, 31.7, 21.2, 17.9, 14.0; HRMS (EI) calcd. for C25H25NO3 [M+ ]: 387.1834, found: 387.1840

Palladium(0)-Catalyzed Methylcyclopropanation of Norbornenes with Vinyl Bromides and Mechanism Study Jiangang Mao, †,‡ Hujun Xie,§Weiliang Bao*,† †Department of Chemistry, Zhejiang University, Hangzhou 310028, Zhejiang, P. R. China ‡School of Metallurgy and Chemical Engineering, Jiangxi University of Science and Technology, 86 Hongqi Avenue, Ganzhou 341000, Jiangxi, P. R. China §School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310035 Zhejiang, P.R. China E-mail: wlbao@zju.edu.cn

Palladium(0)-Catalyzed Methylcyclopropanation of Norbornenes with Vinyl Bromides and Mechanism Study

Jiangang Mao†‡, Hujun Xie§, and Weiliang Bao*†

† Department of Chemistry, Zhejiang University, Hangzhou 310028, Zhejiang, P.R. China

‡ School of Metallurgy and Chemical Engineering, Jiangxi University of Science and Technology, Ganzhou 341000, Jiangxi, P.R. China

§ School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310035, Zhejiang P.R. China

Org. Lett., 2015, 17 (15), pp 3678–3681

DOI: 10.1021/acs.orglett.5b01603

*E-mail: wlbao@zju.edu.cn.

Abstract

An unusual methylcyclopropanation from [2 + 1] cycloadditions of vinyl bromides to norbornenes catalyzed by Pd(OAc)2/PPh3 in the presence of CH3ONa and CH3OH has been established. A methylcyclopropane subunit was installed by a 3-fold domino procedure involving a key protonation course. Preliminary deuterium-labeling studies revealed that the proton came from methyl of CH3OH and also exposed an additional hydrogen/deuterium exchange process. These two proton-concerned reactions were fully chemoselective.

http://pubs.acs.org/doi/abs/10.1021/acs.orglett.5b01603

J. Mao, H. Xie, W. Bao, Org. Lett. 2015, 17, 3678 – 3681

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Cookson’s Dione

• 
  
• CAS No.: 2958-72-7
• Cookson's dione   
• Formula: C11H10O2
• Molecular Weight: 174.19600

Cookson’s Dione

125 W Batch Reaction
A solution of Diels Alder adduct 3[3] (2.61 g, 15 mmol) in degassed EtOAc (150 ml) was irradiated with a pre-warmed 125 W medium pressure mercury lamp in a 150 ml batch reactor equipped with a
Pyrex immersion well for 15 min. The solvent was removed in vacuo and chromatography on silica
(40% EtOAc in hexane to 100% EtOAc) yielded Cookson’s dione 4 as an off-white solid (2.38 g, 91%)


1.5 kW Flow Reaction
A solution of Diels Alder adduct 3 (436 g, 2.5 mol) in degassed EtOAc (0.5 M) was irradiated with the firefly reactor fitted with a Pyrex inner filter and lamp at 1.5 kW at 36 ml/min. The mixture was
concentrated in vacuo to a slurry to which was added hexane. The mixture was filtered, washing
with petroleum ether and the solid dried to give pure Cookson’s dione 4 as an off-white crystalline
solid (387 g, 89%): m.p. 242 - 243°C;

δH (400 MHz, CDCl3) 3.19 – 3.14 (2H, m, 2×CH), 2.95 – 2.90 (2H,m, 2×CH), 2.82 – 2.78 (2H, m, 2×CH), 2.72 – 2.68 (2H, m, 2×CH), 2.04 (1H, app. d, J = 11.4 Hz, CHH),
1.88 (1H, app. d, J = 11.4 Hz, CHH);

 δC (100 MHz, CDCl3) 212. 2 (2×C), 54.9 (2×CH), 44.8 (2×CH), 43.9 (2×CH), 40.6 (CH2), 38.9 (2×CH)

SMILES O=C2[C@@H]1[C@@H]3C[C@@H]4[C@H]1C(=O)[C@H]5[C@H]2[C@H]3[C@H]45

Palladium(0)-Catalyzed Methylcyclopropanation of Norbornenes with Vinyl Bromides and Mechanism Study

Jiangang Mao†‡, Hujun Xie§, and Weiliang Bao*†

† Department of Chemistry, Zhejiang University, Hangzhou 310028, Zhejiang, P.R. China

‡ School of Metallurgy and Chemical Engineering, Jiangxi University of Science and Technology, Ganzhou 341000, Jiangxi, P.R. China

§ School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310035, Zhejiang P.R. China

Org. Lett., 2015, 17 (15), pp 3678–3681

DOI: 10.1021/acs.orglett.5b01603

*E-mail: wlbao@zju.edu.cn.

Abstract

An unusual methylcyclopropanation from [2 + 1] cycloadditions of vinyl bromides to norbornenes catalyzed by Pd(OAc)2/PPh3 in the presence of CH3ONa and CH3OH has been established. A methylcyclopropane subunit was installed by a 3-fold domino procedure involving a key protonation course. Preliminary deuterium-labeling studies revealed that the proton came from methyl of CH3OH and also exposed an additional hydrogen/deuterium exchange process. These two proton-concerned reactions were fully chemoselective.

http://pubs.acs.org/doi/abs/10.1021/acs.orglett.5b01603

J. Mao, H. Xie, W. Bao, Org. Lett. 2015, 17, 3678 – 3681



Paper

http://www.mdpi.com/1420-3049/12/2/271/htm

Molecules 2007, 12(2), 271-282; doi:10.3390/12020271

Full Paper

Synthesis and Biological Evaluation of Rigid Polycyclic Derivatives of the Diels-Alder Adduct Tricyclo[6.2.1.02,7]undeca-4,9-dien-3,6-dione

Felicia Megumi Ito 1, Jacqueline Marques Petroni 1, Dênis Pires de Lima 1, Adilson Beatriz 1,*, Maria Rita Marques 2, Manoel Odorico de Moraes 3, Letícia Veras Costa-Lotufo 3, Raquel  Carvalho Montenegro 3, Hemerson Iury Ferreira Magalhães 3 and Cláudia do Ó Pessoa 3

1

Department of Chemistry, Federal University of Mato Grosso do Sul, Campo Grande, 

MS, Brazil,,

2

Department of Morphophysiology, Federal University of Mato Grosso do Sul, 

Campo Grande, MS, Brazil

3

Department of Physiology and Pharmacology, Federal University of Ceará, 

Fortaleza, CE, Brazil,,,

*

Author to whom correspondence should be addressed;

 Homepage: http://www.dqi.ufms.br/~lp4/adilson.htm.

1. Cookson, R.C.; Grundwell, E.; Hudec, J. Synthesis of cage-like molecules 
2. by irradiation of Diels-Alder adducts. Chem. Ind. (London) 1958, 1003–1004. [Google Scholar]

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NIMBOLIDE

(From left to right) Principal Investigator Associate Professor Gautam Sethi and NUS PhD candidate Ms Zhang Jingwen from the Department of Pharmacology at the NUS Yong Loo Lin School of Medicine led a research which found that a bioactive compound from the neem plant could significantly suppress development of prostate cancer.

Credit: National University of Singapore

Date:September 29, 2016Source:National University of SingaporeSummary:Oral administration of nimbolide, over 12 weeks shows reduction of prostate tumor size by up to 70 per cent and decrease in tumor metastasis by up to 50 per cent, report investigators.

Nimbolide; NSC309909; NSC 309909; Methyl[8-(furan-3-yl)-2a,5a,6a,7-tetramethyl-2,5-dioxo-2a,5a,6,6a,8,9,9a,10a,10b,10c-decahydro-2h,5h-cyclopenta[d]naphtho[2,3-b:1,8-b'c']difuran-6-yl]acetate; CCRIS 5723;

CAS 25990-37-8;
Molecular Formula:	C27H30O7
Molecular Weight:	466.5229 g/mol

Oral administration of nimbolide, over 12 weeks shows reduction of prostate tumor size by up to 70 per cent and decrease in tumor metastasis by up to 50 per cent

A team of international researchers led by Associate Professor Gautam Sethi from the Department of Pharmacology at the Yong Loo Lin School of Medicine at the National University of Singapore (NUS) has found that nimbolide, a bioactive terpenoid compound derived from Azadirachta indica or more commonly known as the neem plant, could reduce the size of prostate tumor by up to 70 per cent and suppress its spread or metastasis by half.

Prostate cancer is one of the most commonly diagnosed cancers worldwide. However, currently available therapies for metastatic prostate cancer are only marginally effective. Hence, there is a need for more novel treatment alternatives and options.

“Although the diverse anti-cancer effects of nimbolide have been reported in different cancer types, its potential effects on prostate cancer initiation and progression have not been demonstrated in scientific studies. In this research, we have demonstrated that nimbolide can inhibit tumor cell viability — a cellular process that directly affects the ability of a cell to proliferate, grow, divide, or repair damaged cell components — and induce programmed cell death in prostate cancer cells,” said Assoc Prof Sethi.

Nimbolide: promising effects on prostate cancer

Cell invasion and migration are key steps during tumor metastasis. The NUS-led study revealed that nimbolide can significantly suppress cell invasion and migration of prostate cancer cells, suggesting its ability to reduce tumor metastasis.

The researchers observed that upon the 12 weeks of administering nimbolide, the size of prostate cancer tumor was reduced by as much as 70 per cent and its metastasis decreased by about 50 per cent, without exhibiting any significant adverse effects.

“This is possible because a direct target of nimbolide in prostate cancer is glutathione reductase, an enzyme which is responsible for maintaining the antioxidant system that regulates the STAT3 gene in the body. The activation of the STAT3 gene has been reported to contribute to prostate tumor growth and metastasis,” explained Assoc Prof Sethi. “We have found that nimbolide can substantially inhibit STAT3 activation and thereby abrogating the growth and metastasis of prostate tumor,” he added.

The findings of the study were published in the April 2016 issue of the scientific journal Antioxidants & Redox Signaling. This work was carried out in collaboration with Professor Goh Boon Cher of Cancer Science Institute of Singapore at NUS, Professor Hui Kam Man of National Cancer Centre Singapore and Professor Ahn Kwang Seok of Kyung Hee University.

Neem — The medicinal plant

The neem plant belongs to the mahogany tree family that is originally native to India and the Indian sub-continent. It has been part of traditional Asian medicine for centuries and is typically used in Indian Ayurvedic medicine. Today, neem leaves and bark have been incorporated into many personal care products such as soaps, toothpaste, skincare and even dietary supplements.

Future Research

The team is looking to embark on a genome-wide screening or to perform a large-scale study of proteins to analyse the side-effects and determine other potential molecular targets of nimbolide. They are also keen to investigate the efficacy of combinatory regimen of nimbolide and approved drugs such as docetaxel and enzalutamide for future prostate cancer therapy.

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Journal Reference:

1. Jingwen Zhang, Kwang Seok Ahn, Chulwon Kim, Muthu K. Shanmugam, Kodappully Sivaraman Siveen, Frank Arfuso, Ramar Perumal Samym, Amudha Deivasigamanim, Lina Hsiu Kim Lim, Lingzhi Wang, Boon Cher Goh, Alan Prem Kumar, Kam Man Hui, Gautam Sethi. Nimbolide-Induced Oxidative Stress Abrogates STAT3 Signaling Cascade and Inhibits Tumor Growth in Transgenic Adenocarcinoma of Mouse Prostate Model. Antioxidants & Redox Signaling, 2016; 24 (11): 575 DOI:10.1089/ars.2015.6418

A PAPER

NIMBOLIDE 1

http://pubs.rsc.org/en/content/articlelanding/2015/ra/c5ra16071e#!divAbstract

Nimbolide (1): Pale yellow crystals; C27H30O7;

FT-IR (KBr, υmax, cm -1): 2978, 1778, 1730, 1672, 1433, 1296, 1238, 1192, 1153, 1069, 951, 827, 750;

1H NMR (500 MHz, CDCl3) δH: 7.32 (t, J = 1.5 Hz, 1H), 7.28 (d, J = 9.5 Hz, 1H), 7.22 (s, 1H), 6.25 (m, 1H), 5.93 (d, J = 10.0 Hz, 1H), 5.53 (m, 1H), 4.62 (dd, J = 3.67 Hz, 12 .5 Hz, 1H), 4.27 (d, J = 3.5 Hz, 1H), 3.67 (d, J = 9.0 Hz, 1H), 3.54 (s, 3H), 3.25 (dd, J = 5.0 Hz, 16.25 Hz, 1H), 3.19 (d, J = 12.5 Hz, 1H), 2.73 (t, J = 5.5 Hz, 1H), 2.38 (dd, J = 5.5 Hz, 16.25 Hz, 1H), 2.22 (dd, J = 6.5 Hz, 12.0 Hz, 1H), 2.10 (m, 1H), 1.70 (s, 3H), 1.47 (s, 3H), 1.37 (s, 3H), 1.22 (s, 3H);

13C NMR (125 MHz, CDCl3) δC: 200.8 (CO), 175.0 (COO), 173.0 (COO), 149.6 (CH), 144.8 (C), 143.2 (CH), 138.9 (CH), 136.4 (C), 131.0 (CH), 126.5 (C), 110.3 (CH), 88.5 (CH), 82.9 (CH), 73.4 (CH), 51.8 (OCH3), 50.3 (C), 49.5 (CH), 47.7 (CH), 45.3 (C), 43.7 (C), 41.2 (CH2), 41.1 (CH), 32.1 (CH2), 18.5 (CH3), 17.2 (CH3), 15.2 (CH3), 12.9 (CH3);

HR-MS (m/z): 467.20795 [(M+H)+ ].

Content Page No 1 1H NMR spectrum of nimbolide S1 2 13C NMR spectrum of nimbolide S2 3 Mass spectrum of nimbolide

Dr Gautam Sethi

phcgs@nus.edu.sg
Tel.: (65)6516 3267
Fax: (65)6873 7690

Academic Qualifications
BSc. Chem. (Hons)	1998	Banaras Hindu University, Varanasi, India.
MSc. Biochemistry	2000	Banaras Hindu University, Varanasi, India.
Ph.D. Biotechnology	2004	Banaras Hindu University, Varanasi, India.
Appointments to Date
Assistant Professor	2008-date	Department of Pharmacology, National University of Singapore, Singapore
Postdoctoral Fellow	2004-2007	Department of Experimental Therapeutics, The University of Texas. MD Anderson Cancer Center, Houston TX USA.
Senior Research Fellow	2002-2004	(CSIR-NET) at School of Biotechnology, Banaras Hindu University, Varanasi, India.
Junior Research Fellow	2000-2002	(CSIR-NET) at School of Biotechnology, Banaras Hindu University, Varanasi, India.
Honours and Awards
2007	Ramalingaswamy fellowship from Department of Biotechnology, Government of India for outstanding research contributions in the field of Cancer Biology.
2002	Senior Research Fellowship award, Council of Scientific and Industrial Research, New Delhi, India.
2000	Junior Research Fellowship award, Council of Scientific and Industrial Research, New Delhi, India.
Research Interests
Selected Publications
Reviews and Book Chapters

/////////NIMBOLIDE, CANCER, NEEM, PROSTRATE, Gautam Sethi, National University of Singapore

CC1=C2C(CC1C3=COC=C3)OC4C2(C(C5(C6C4OC(=O)C6(C=CC5=O)C)C)CC(=O)OC)C

A simple scale-up strategy for organolithium chemistry in flow mode: From feasibility to kilogram quantities

Synthesis of 2-Trifluoromethyl-4-fluorophenylboronic acid (2a)
2a: 2-Trifluoromethyl-4-fluorophenylboronic acid After reaching steady-state, the outcoming stream was quenched for 25 min (765 mmol) on 797 mL citric acid (10% in water) at 0 °C. After full addition, the mixture was stirred for 30 min at 0 °C and then warmed up to r.t. and stirred for another hour. The phases were separated and the water phase was extracted twice with 1.8 L isopropyl acetate. The organic phases were combined, washed with 20% NaClsolution (1.8 L) and dried in vacuum to yield the final product. The product was obtained as a slightly yellow solid. 146.1 g (HPLC purity at 210 nm = 97.4%). Yield = 89%.

1H NMR (400 MHz, DMSO-d6): δ = 8.00 (dd, J = 8.3, 6.6 Hz, 1H, Ar-H), 7.52 (dd, J = 9.9, 2.5 Hz, 1H, Ar-H), 7.55−7.45 (m, 1H, Ar-H) ppm.

13C NMR (100 MHz, DMSO-d6): δ = 162.6 (d, J = 247.0 Hz, CF), 138.1 (d, J = 7.9 Hz), 134.8 (dq, J = 31.6, 7.7 Hz), 133.8, 124.5 (dq, J = 274.8, 3.00 Hz, CF3), 118.4 (d, J = 19.2 Hz), 113.3 (dq, J = 24.2, 6.1 Hz) ppm.

 19F NMR (376 MHz, DMSO-d6): δ = −57.8 (s, 3F, CF3), −111.2 (s, 1F, CF) ppm. 11B-NMR (128 MHz, DMSO-d6): δ = 13.8 ppm. Analytical data is identical with the literature.1 [1] A. Hafner, M. Meisenbach, J. Sedelmeier, Org. Lett. 2016, 18, 3630-3633.

A simple scale-up strategy for organolithium chemistry in flow mode: From feasibility to kilogram quantities Andreas Hafner, Paolo Filipponi, Lorenzo Piccioni, Mark Meisenbach, Berthold Schenkel, Francesco Venturoni and Joerg Sedelmeier* Novartis Pharma AG, Fabrikstrasse 14, 4002 Basel, Switzerland Joerg.Sedelmeier@novartis.com