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1-(8-Chloro-3-methyl-1H-pyrazolo[4,3-c]cinnolin-1-yl)-2-(2-chlorophenyl)ethanone

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi-110062, India
*
Author to whom correspondence should be addressed.
Molbank 2011, 2011(4), M744; https://doi.org/10.3390/M744
Received: 23 September 2011 / Accepted: 11 November 2011 / Published: 16 November 2011

Abstract

1-(8-Chloro-3-methyl-1H-pyrazolo[4,3-c]cinnolin-1-yl)-2-(2-chlorophenyl)ethanone 2 has been synthesized through condensation of 3-acetyl-6-chloro-1H-cinnolin-4-one 1 with 2-(2-chlorophenyl)acetohydrazide in polar aprotic solvent containing catalytic amount of conc. HCl. The structure of the title compound 2 was established on the basis of IR, 1H-NMR, 13C-NMR and mass spectral data.
Keywords: cinnoline; pyrazole; 2-(2-Chlorophenyl)acetohydrazide cinnoline; pyrazole; 2-(2-Chlorophenyl)acetohydrazide
Cinnoline (or 1,2-diazanaphthalene) has obvious potential as antibacterial agent and along with other heterocyclic moieties showed a wide spectrum of pharmacological activities like antimicrobial, anti-inflammatory, analgesic, anticancer, antihypertensive and neuroleptic properties [1,2,3,4,5]. In continuation of our previous work on diazines and benzfused heterocyclic compounds [6,7,8], we are reporting herein the synthesis of 1-(8-Chloro-3-methyl-1H-pyrazolo[4,3-c]cinnolin-1-yl)-2-(2-chlorophenyl)ethanone 2.
In the 1H-NMR spectrum (CDCl3 solvent) of compound 2, the characteristic singlet of cinnoline-NH proton (D2O exchangeable) in compound 1 at 13.90 ppm disappeared, and the singlet of methyl group (-COCH3) shifted upfield to 2.36 ppm along with a new signal of methylene group (–CH2-) at 4.39 ppm. Moreover, the cyclic carbonyl carbon signal disappeared in the 13C-NMR spectrum of compound 2. The fact was also supported by the mass spectrum of compound 2 which showed molecular ion peak (M+) at m/z 370.04 along with two characteristic peaks at 372.04 (M++2) and 374.04 (M++4). The values are in complete agreement with the structure assigned.
Scheme 1. Synthetic route for the title compound 2.
Scheme 1. Synthetic route for the title compound 2.
Molbank 2011 m744 sch001
Synthesis of 1-(8-Chloro-3-methyl-1H-pyrazolo[4,3-c]cinnolin-1-yl)-2-(2-chlorophenyl)ethanone 2
Accurately weighed quantities of 1 (0.5 g, 2 mmol) and 2-(2-Chlorophenyl)acetohydrazide (2.5 mmol) were mixed on a magnetic stirrer for 0.5 h in anhydrous 1,4-dioxane (25 mL) containing 0.2 mL of concentrated hydrochloric acid. The resulting mixture was boiled under reflux for 14 h. After completion of reaction (monitored by TLC) the reaction mixture was allowed to cool, concentrated under reduced pressure and poured in to ice-cold water with constant stirring. The product obtained was filtered, dried and then purified through column chromatography (Hexane/AcOEt 4:1) to afford the titled compound 2.
Yield 56%, m.p. 206–208 °C, Yellow amorphous solid.
IR (KBr) cm−1: 1664 (C=O), 1593 (C=N), 1569 (C=C), 1263, 1166 (-C-N=N-), 746 (C-Cl).
1H NMR (300 MHz, CDCl3): δ (ppm) 2.36 (s, 3H, CH3), δ 4.39 (s, 2H, CH2), 7.23–7.32 (m, 4H, HPhenyl), δ 7.39 (br. s, 3H, HCinnoline).
1H NMR (300 MHz, DMSO-d6): δ (ppm) 2.25 (s, 3H, CH3), δ 4.35 (s, 2H, CH2), δ 7.27–7.32 (m, 2H, HCinnoline), 7.39–7.52 (m, 4H, HPhenyl), δ 7.66 (br s, 1H, HCinnoline).
13C NMR (75 MHz, CDCl3): δ (ppm) 12.0 (CH3), 67.0 (CH2), 116.7, 117.2, 126.8, 128.7, 129.4, 129.8, 131.5, 131.8, 134.7, 139.2, 151.2, 159.0, 166.6 (C=O).
DART-MS m/z: 370.04 (M+), 372.04 (M++2), 374.04 (M++4).
Anal. Calcd for C18H12Cl2N4O: C, 58.24; H, 3.26; N, 15.09. Found: C, 58.44; H, 3.31; N, 15.04.

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3

Acknowledgments

One of the authors (R.K. Tonk) expresses sincere thanks to the University Grant Commission (UGC), New Delhi, India, for the award of Rajiv Gandhi National Senior Research Fellowship (RGNSRF). The authors are also thankful to Central Drug Research Institute (CDRI), Lucknow, India for recording spectral data.

References

  1. Nargund, L.V.G.; Badiger, V.V.; Yarnal, S.M. Synthesis and antimicrobial and anti-inflammatory activities of substituted 2-mercapto-3-(n-aryl)pyrimido[5,4-c]cinnolin-4-(3H)-ones. J. Pharm. Sci. 1992, 81, 365–366. [Google Scholar] [CrossRef] [PubMed]
  2. Kametani, T.; Kigasawa, K.; Hiiragi, M.; Ishimaru, H.; Wagatsuma, N.; Kohagisawa, T.; Nakamura, T. Novel Type of Analgesic- Synthesis and Analgesic Activity. Heterocycles 1980, 14, 449–451. [Google Scholar] [CrossRef]
  3. Ruchelman, A.L.; Singh, S.K.; Ray, A.; Wu, X.; Yang, J.-M.; Zhou, N.; Liu, A.; Liu, L.F.; LaVoie, E.J. 11H-Isoquino[4,3-c]cinnolin-12-ones: Novel anticancer agents with potent topoisomerase I-targeting activity and cytotoxicity. Bioorg. Med. Chem. 2004, 12, 795–806. [Google Scholar] [CrossRef] [PubMed]
  4. Pinna, G.A.; Salis, E.; Berta, D.; Gavini, E.; D’Amico, M. Synthesis and pharmacological evaluaion of 4a-methyl-4,4a,5,6-tetrahydrothieno[2,3-h]cinnolin-3(2H)-ones. Farmaco 1997, 52, 29–33. [Google Scholar] [PubMed]
  5. Stanczak, A.; Kwapiszewski, W.; Szadowska, A.; Pakulska, W. Synthesis and action on the central nervous system of some N2-substituted cinnoline derivatives. Pharmazie 1994, 49, 406–412. [Google Scholar] [CrossRef] [PubMed]
  6. Kumar, S.; Bawa, S.; Drabu, S. N-[(2-chloro-6-mthylquinolin-3-yl)methyl]aniline. Molbank 2009, 2009, M618. [Google Scholar] [CrossRef]
  7. Mishra, R.; Siddiqui, A.A.; Kumar, R.; Kumar, S. 6-Oxo-3-phenyl-5,6-dihydropyridazine-1(4H)-carbohydrazide. Molbank 2010, 2010, M652. [Google Scholar] [CrossRef]
  8. Bawa, S.; Kumar, R.; Chawla, G.; Kumar, S.; Mishra, R. (8-Chloro-3-methyl-1H-pyrazolo[4,3-c]cinnolin-1-yl) (pyridin-4-yl)methanone. Molbank 2010, 2010, M688. [Google Scholar] [CrossRef]
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