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

Mohammad Mahdavi; Maryam Bialam; Mina Saeedi; Farnaz Jafarpour; Alireza Foroumadi; Abbas Shafiee

doi:10.1055/s-0034-1379499

Synlett, Inhaltsverzeichnis

Synlett 2015; 26(02): 173-176
DOI: 10.1055/s-0034-1379499

letter

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

Mohammad Mahdavi

^aDepartment 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

^bSchool of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran

,

Mina Saeedi

^cPersian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran

,

Farnaz Jafarpour

^bSchool of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran

,

Alireza Foroumadi

^aDepartment 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*

^aDepartment 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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Abstract

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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

Volltext

Referenzen

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.

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