Synthesis of Novel Benzo[6,7][1,4]oxazepino[4,5-a]quinazolinone Derivatives via Transition-Metal-Free Intramolecular Hydroamination

Mohammad Mahdavi; Niloufar Foroughi; Mina Saeedi; Maryam Karimi; Heshmatollah Alinezhad; Alireza Foroumadi; Abbas Shafiee; Tahmineh Akbarzadeh

doi:10.1055/s-0033-1340310

Synlett, Table of Contents

Synlett 2014; 25(3): 385-388
DOI: 10.1055/s-0033-1340310

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Synthesis of Novel Benzo[6,7][1,4]oxazepino[4,5-a]quinazolinone Derivatives via Transition-Metal-Free Intramolecular Hydroamination

Mohammad Mahdavi

^aDepartment of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran

,

Niloufar Foroughi

^aDepartment of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran

,

Mina Saeedi

^aDepartment of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran

,

Maryam Karimi

^aDepartment of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran

,

Heshmatollah Alinezhad

^bFaculty of Chemistry, Mazandaran University, Babolsar, Iran

,

Alireza Foroumadi

^aDepartment of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran

,

Abbas Shafiee

^aDepartment of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran

,

Tahmineh Akbarzadeh*

^cDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14176, Iran

^dPersian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran Fax: +98(21)66461178 Email: akbarzad@tums.ac.ir

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Abstract

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Abstract

Novel benzo[6,7][1,4]oxazepino[4,5-a]quinazolinone derivatives were synthesized through an efficient 7-exo-dig hydroamination of 3-substituted-2-[2-(prop-2-yn-1-yloxy)phenyl]-2,3-dihydroquinazolin-4(1H)-ones in the presence of potassium tert-butoxide (KOt-Bu) in DMF at 130 °C.

Key words

hydroamination - 2-aminobenzamides - terminal alkynes - 7-exo-dig - N-heterocycles

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References

References and Notes
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27 Synthesis of Benzo[6,7][1,4]oxazepino[4,5-a]quinazolinone Derivatives 2 – General Procedure A mixture of 3-substituted 2-[2-(prop-2-yn-1-yloxy)phenyl]-2,3-dihydroquinazolin-4(1H)-one 1 (1 mmol) and KOt-Bu (2 mmol) in DMF (5 mL) was stirred at 130 °C for 3–4 h. Upon completion of reaction, checked by TLC, the reaction mixture was poured into cold H₂O, the precipitate was filtered off, and the residue was purified using plate chromatography eluting with PE–EtOAc (4:1). 8-Butyl-1-methyl-7b,8-dihydro-9H-benzo[6,7][1,4]-oxazepino[4,5-a]quinazolin-9-one (2a) Yield 0.23 g (68%); yellow oil. IR (KBr): 3060, 2957, 2850, 1659 (C=O), 1614, 1482 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 0.87 (t, J = 7.2 Hz, 3 H, NCH₂CH₂CH₂CH ₃), 1.27–1.33 (m, 2 H, NCH₂CH₂CH ₂CH₃), 1.54–1.63 (m, 2 H, NCH₂CH ₂CH₂CH₃), 2.02 (s, 3 H, CH₃), 2.84–2.91 (m, 1 H, NCH _2aCH₂CH₂CH₃), 4.04 (m, 1 H, NCH _2bCH₂CH₂CH₃), 5.76 (s, 1 H, CH, H₂), 6.67 (s, 1 H, CH), 6.72 (d, J = 7.6 Hz, 1 H, H₁₃), 6.82 (t, J = 7.6 Hz, 1 H, H₁₁), 6.88 (d, J = 7.0 Hz, 1 H, H₄), 6.99 (t, J = 7.0 Hz, 1 H, H₆), 7.05 (d, J = 7.0 Hz, 1 H, H₇), 7.24 (dt, J = 7.0, 1.2 Hz, 1 H, H₅), 7.29 (dt, J = 7.6, 1.2 Hz, 1 H, H₁₂), 7.77 (dd, J = 7.6, 1.2 Hz, 1 H, H₁₀). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 14.1, 20.0, 20.3, 30.3, 45.3, 70.6, 107.1, 113.7, 115.9, 119.4, 121.2, 123.9, 124.9, 128.3, 130.5, 131.2, 134.1, 143.5, 143.7, 155.1, 162.0. Anal. Calcd for C₂₁H₂₂N₂O₂: C, 75.42; H, 6.63; N, 8.38. Found: C, 75.28; H, 6.78; N, 8.19. Data for compounds 2b–i are given in the Supporting Information.

Supplementary Material

Supporting Information