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
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Publikationsverlauf

Received: 13. September 2014

Accepted after revision: 29. Oktober 2014

Publikationsdatum:
09. Dezember 2014 (online)


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.

Supporting Information

 
  • References and Notes

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  • 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.