PDF herunterladen
Synlett 2015; 26(02): 173-176
DOI: 10.1055/s-0034-1379499
letter
© Georg Thieme Verlag Stuttgart · New York

Efficient Synthesis of 2-Methylenethiazolo[2,3-b]quinazolinone Derivatives

Mohammad Mahdavi
a   Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran   eMail: shafieea@tums.ac.ir
,
Maryam Bialam
b   School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran
,
Mina Saeedi
c   Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran
,
Farnaz Jafarpour
b   School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran
,
Alireza Foroumadi
a   Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran   eMail: shafieea@tums.ac.ir
,
Abbas Shafiee*
a   Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran   eMail: shafieea@tums.ac.ir
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 13. September 2014

Accepted after revision: 29. Oktober 2014

Publikationsdatum:
09. Dezember 2014 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik


Abstract

Substituted o-amino-N-(prop-2-yn-1-yl) aromatic amides easily reacted with carbon disulfide (CS2) in the presence of potassium hydroxide (KOH) in EtOH under reflux conditions. Cyclization reaction followed by a favored 5-exo-dig ring closure afforded 2-methylene-­thiazolo[2,3-b]quinazolinone derivatives in good yields.

Key words

2-methylene-thiazolo[2,3-b]quinazolinones - propargylamine - carbon disulfide - fused quinazolinone - 5-exo-dig

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1379499.
  • Supporting Information
 

  • References and Notes

  • 1 Khan I, Ibrar A, Abbas N, Saeed A. Eur. J. Med. Chem. 2014; 76: 193
    Crossref
  • 2 Chen X, Du Y, Sun H, Wang F, Kong L, Sun M. Bioorg. Med. Chem. Lett. 2014; 24: 884
    Crossref
  • 3 Ugale VG, Bari SB. Eur. J. Med. Chem. 2014; 80: 447
    Crossref
  • 4 Balakumar C, Lamba P, Kishore DP, Narayana BL, Rao KV, Rajwinder K, Rao AR, Shireesha B, Narsaiah B. Eur. J. Med. Chem. 2010; 45: 4904
    Crossref
  • 5 Hu S, Xie G, Zhang DX, Davis C, Long W, Hu Y, Wang F, Kang X, Tan F, Ding L, Wang Y. Bioorg. Med. Chem. Lett. 2012; 22: 6301
    Crossref
  • 6 Fowler KW, Huang D, Kesicki EA, Ooi HC, Oliver A, Ruan F, Treiberg J, Puri KD. US Patent RE44599, 2013
  • 7 Gali R, Banothu J, Porika M, Velpula R, Hnamte S, Bavantula R, Abbagani S, Busi S. Bioorg. Med. Chem. Lett. 2014; 24: 4239
    Crossref
  • 8 Saeva GA, Georgiev VS. US Patent 4738964, 1988
    • 9a Seybold G, Wuerzer B. US Patent 4473391, 1984
    • 9b Seybold G, Wuerzer B. US Patent 4486221, 1984
  • 10 Sachdev HS, Dhami KS, Atwal MS. Tetrahedron 1961; 14: 304
    Crossref
  • 11 Dhami KS, Sachdev HS, Narang KS. J. Sci. Ind. Res. 1956; 15: 690
  • 12 Shiau C.-Y, Chern J.-W, Liu K.-C, Chan C.-H, Yen M.-H, Cheng M.-C, Wang Y. J. Heterocycl. Chem. 1990; 27: 1467
    Crossref
    • 13a Mahdavi M, Asadi M, Saeedi M, Rezaei Z, Moghbel H, Foroumadi A, Shafiee A. Synlett 2012; 23: 2521
      Artikel in Thieme Connect
    • 13b Mahdavi M, Foroughi N, Saeedi M, Karimi M, Foroumadi A, Alinezhad H, Shafiee A, Akbarzadeh T. Synlett 2014; 25: 385
      Artikel in Thieme Connect
    • 13c Esmaeili-Marandi F, Saeedi M, Mahdavi M, Yavari I, Foroumadi A, Shafiee A. Synlett 2014; 25: 2605
      Artikel in Thieme Connect
  • 14 Jablonski JJ, Basu D, Engel DA, Geysen HM. Bioorg. Med. Chem. 2012; 20: 487
    Crossref
  • 15 Ren X.-F, Turos E, Lake CH, Churchill MR. J. Org. Chem. 1995; 60: 6468
    Crossref
  • 16 Ren X.-F, Turos E. Tetrahedron Lett. 1993; 34: 1575
    Crossref
    • 17a Baldwin JE. J. Chem. Soc., Chem. Commun. 1976; 734
    • 17b Baldwin JE, Thomas RC, Kruse LI, Silberman L. J. Org. Chem. 1977; 42: 3846
      Crossref
  • 18 Pura MS, Sachdev HS, Ralhan NK. Indian J. Chem. 1964; 2: 258
  • 19 Synthesis of 2-Methylene-thiazolo[2,3-b]quinazolinone Derivatives 11 – General ProcedureA mixture of substituted o-amino-N-(prop-2-yn-1-yl) aromatic amides 9 (1 mmol), CS2 (10, 2 mmol), and KOH (1 mmol) in EtOH (8 mL) was heated at reflux for 3–8 h. After completion of reaction (checked by TLC), the reaction mixture was cooled to r.t. and poured into cold H2O. The precipitate was filtered off to obtain pure products 11 with no need for further purification.2-Methylene-2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one (11a)Yield 0.18 g (85%); white solid; mp 220–222 °C (lit.11 202 °C). IR (KBr): 2937, 1665, 1582, 1553 cm–1. 1H NMR (400 MHz, CDCl3): δ = 5.12 (t, J = 2.4 Hz, 2 H, CH2), 5.37 (q, J = 2.4 Hz, 1 H, =CH2), 5.50 (q, J = 2.4 Hz, 1 H, =CH2), 7.42 (td, J = 7.6, 0.8 Hz, 1 H, H7), 7.56 (dd, J = 7.6, 0.8 Hz, 1 H, H9), 7.72 (td, J = 7.6, 1.5 Hz, 1 H, H8), 8.22 (dd, J = 7.6, 1.5 Hz, 1 H, H6). 13C NMR (100 MHz, CDCl3): δ = 54.2, 108.3, 119.3, 126.2, 126.3, 126.6, 133.1, 134.8, 148.8, 158.1, 159.9. Anal. Calcd for C11H8N2OS: C, 61.09; H, 3.73; N, 12.95. Found: C, 60.87; H, 3.58; N, 13.14.7-Methyl-2-methylene-2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one (11b)Yield 0.18 g (80%); deep yellow solid; mp 160–162 °C (lit.11 150 °C). IR (KBr): 1669, 1621, 1581 m–1. 1H NMR (400 MHz, CDCl3): δ = 2.47 (s, 3 H, CH3), 5.11 (t, J = 2.4 Hz, 2 H, CH2), 5.35 (q, J = 2.4 Hz, 1 H, =CH2), 5.48 (q, J = 2.4 Hz, 1 H, =CH2), 7.45 (d, J = 8.4 Hz, 1 H, H9), 7.53 (dd, J = 8.4, 1.6 Hz, 1 H, H8), 8.00 (s, 1 H, H6). 13C NMR (100 MHz, CDCl3): δ = 21.2, 54.2, 108.1, 119.0, 126.0, 126.1, 133.3, 136.1, 136.4, 146.8, 157.0, 159.9. Anal. Calcd for C12H10N2OS: C, 62.59; H, 4.38; N, 12.16. Found: C, 62.41; H, 4.52; N, 11.97.7,8-Dimethoxy-2-methylene-2H-thiazolo[2,3-b]quinazolin-5(3H)-one (11c)Yield 0.21 g (75%); deep yellow solid; mp 221–223 °C. IR (KBr): 1672, 1605, 1580 cm–1. 1H NMR (400 MHz, CDCl3): δ = 3.98 (s, 3 H, OCH3), 4.00 (s, 3 H, OCH3), 5.12 (t, J = 2.4 Hz, 2 H, CH2), 5.35 (q, J = 2.4 Hz, 1 H, =CH2), 5.48 (q, J = 2.4 Hz, 1 H, =CH2), 6.98 (s, 1 H, H9), 7.52 (s, 1 H, H6). 13C NMR (100 MHz, CDCl3): δ = 54.3, 56.2, 56.3, 105.5, 106.9, 108.1, 117.2, 133.4, 145.2, 148.5, 155.1, 156.4, 159.4. Anal. Calcd for C13H12N2O3S: C, 56.51; H, 4.38; N, 10.14. Found: C, 56.34; H, 4.50; N, 9.96.8-Chloro-2-methylene-2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one (11d)Yield 0.17 g (70%); off-white solid; mp 170–171 °C (lit.18 167 °C). IR (KBr): 2918, 1685, 1602, 1568 cm–1. 1H NMR (400 MHz, CDCl3): δ = 5.27 (t, J = 1.9 Hz, 2 H, CH2), 5.37 (q, J = 1.9 Hz, 1 H, =CH2), 5.61 (q, J = 1.9 Hz, 1 H, =CH2), 7.37 (dd, J = 8.8, 2.0 Hz, 1 H, H7), 7.62 (d, J = 2.0 Hz, 1 H, H9), 8.27 (d, J = 8.8 Hz, 1 H, H6). 13C NMR (100 MHz, CDCl3): δ = 53.6, 115.2, 117.2, 123.3, 125.5, 125.8, 128.4, 149.0, 157.6, 159.5, 163.8. Anal. Calcd for C11H7ClN2OS: C, 52.70; H, 2.81; N, 11.17. Found: C, 52.91; H, 2.68; N, 10.92.7-Chloro-2-methylene-2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one (11e)Yield 0.17 g (70%); white solid; mp 192–192 °C (lit.10 193 °C). IR (KBr): 2915, 1681, 1609, 1574 cm–1. 1H NMR (400 MHz, CDCl3): δ = 5.11 (s, 2 H, CH2), 5.37 (d, J = 2.0 Hz, 1 H, =CH2), 5.50 (d, J = 2.0 Hz, 1 H, =CH2), 7.60 (d, J = 7.1 Hz, 1 H, H9), 7.62 (dd, J = 7.1, 2.0 Hz, 1 H, H8), 8.27 (d, J = 2.0 Hz, 1 H, H6). 13C NMR (100 MHz, CDCl3): δ = 54.2, 108.6, 117.1, 123.6, 126.1, 127.8, 130.8, 135.1, 146.7, 157.2, 158.5. Anal. Calcd for C11H7ClN2OS: C, 52.70; H, 2.81; N, 11.17. Found: C, 52.57; H, 2.93; N, 11.28.2-Methylene-2,3-dihydro-5H-benzo[g]thiazolo[2,3-b]quinazolin-5-one (11f)Yield 0.17 g (65%); yellow solid; mp 190–192 °C. IR (KBr): 1628, 1573, 1401 cm–1. 1H NMR (400 MHz, CDCl3): δ = 5.13–5.15 (m, 2 H, CH2), 5.37–5.38 (m, 1 H, =CH2), 5.50–5.51 (m, 1 H, =CH2), 7.52 (t, J = 6.5 Hz, 1 H, H9), 7.62 (t, J = 6.5 Hz, 1 H, H8), 7.98 (d, J = 6.5 Hz, 1 H, H10), 8.00 (s, 1 H, H11), 8.07 (d, J = 6.5 Hz, 1 H, H7), 8.13 (s, 1 H, H6). 13C NMR (100 MHz, CDCl3): δ = 53.9, 108.1, 116.8, 123.1, 123.6, 125.8, 126.2, 128.3, 128.6, 128.7, 128.8, 129.4, 137.0, 163.2, 163.6. Anal. Calcd for C15H10N2OS: C, 67.65; H, 3.78; N, 10.52. Found: C, 67.83; H, 3.57; N, 10.37.2-Methylene-8-nitro-2H-thiazolo[2,3-b]quinazolin-5(3H)-one (11g)Yield 0.13 g (50%); yellow solid; mp 180–182 °C. IR (KBr): 1669, 1535, 1613, 1488, 1350 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 5.12 (t, J = 1.9 Hz, 2 H, CH2), 5.35 (q, J = 1.9 Hz, 1 H, =CH2), 5.48 (q, J = 1.9 Hz, 1 H, =CH2), 6.49 (dd, J = 1.7 Hz, 1 H, H9), 6.66 (dd, J = 6.9, 1.7 Hz, 1 H, H7), 7.72 (d, J = 6.9 Hz, 1 H, H6). 13C NMR (100 MHz, DMSO-d 6): δ = 53.8, 105.9, 108.2, 114.1, 127.3, 133.3, 150.3, 154.5, 156.7, 157.7, 158.4. Anal. Calcd for C11H7N3O3S: C, 50.57; H, 2.70; N, 16.08. Found: C, 50.39; H, 2.57; N, 15.87.2-Methylene-2,3-dihydro-5H-pyrido[2,3-d]thiazolo[3,2-a]pyrimidin-5-one (11h)Yield 0.10 g (45%); deep yellow solid; mp 180–182 °C. IR (KBr): 2915, 1681, 1609 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 5.22 (t, J = 1.5 Hz, 2 H, CH2), 5.63 (q, J = 1.5 Hz, 1 H, =CH2), 5.65 (q, J = 1.5 Hz, 1 H, =CH2), 6.60 (dd, J = 6.2, 3.8 Hz, 1 H, H7), 8.04 (dd, J = 6.2, 1.5 Hz, 1 H, H6), 8.17 (dd, J = 3.8, 1.5 Hz, 1 H, H8). 13C NMR (100 MHz, DMSO-d 6): δ = 51.9, 105.5, 111.8, 120.3, 120.9, 123.3, 140.0, 153.4, 159.7, 168.6. Anal. Calcd for C10H7N3OS: C, 55.29; H, 3.25; N, 19.34. Found: C, 55.42; H, 3.36; N, 19.52.