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Synlett 2014; 25(3): 385-388
DOI: 10.1055/s-0033-1340310
letter
© Georg Thieme Verlag Stuttgart · New York

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

Mohammad Mahdavi
a   Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran
,
Niloufar Foroughi
a   Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran
,
Mina Saeedi
a   Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran
,
Maryam Karimi
a   Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran
,
Heshmatollah Alinezhad
b   Faculty of Chemistry, Mazandaran University, Babolsar, Iran
,
Alireza Foroumadi
a   Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran
,
Abbas Shafiee
a   Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran
,
Tahmineh Akbarzadeh*
c   Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14176, Iran
d   Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran   Fax: +98(21)66461178   Email: akbarzad@tums.ac.ir
› Author Affiliations
Further Information

Publication History

Received: 10 October 2013

Accepted after revision: 01 November 2013

Publication Date:
06 December 2013 (online)

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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

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • 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.