A New, Simple, One-Pot Route for the Synthesis of Triazepin-8-one Derivatives

Abstract

A novel procedure for constructing triazepin-8-one skeletons under mild conditions in one pot was developed. The access to triazepin-8-ones was achieved via direct amination of imidazol-6-ones with aqueous ammonia and cyclization with formaldehyde. The experimental simplicity and moderate to good yields are the main features of this method.

Key words

imidazol-6-ones - one-pot - triazepin-8-one - ring-opening - cyclization

• References and Notes

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• 18 General Procedure for the Preparation of Compound 4a: Dihydropyrroloimidazol-6-one (1a; 1.0 mmol) was dissolved in NH₃ (10.0 mL). The reaction was stirred at 50 °C and monitored by TLC, after completion, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (CH₂Cl₂–MeOH, 15:1) to give the pure product 4a.
• 19 Typical Data for a Representative Compound; 5-Amino-1-[2-{[(6-chloropyridin-3-yl)methyl]amino}ethyl]-2-methyl-4-nitro-1,2-dihydro-3H-pyrrol-3-one (4a): This compound was obtained as a white solid by using the above method with the yield of 91%; mp 175.6–176.5 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.56 (s, 1 H), 8.35 (d, J = 2.0 Hz, 1 H), 7.80 (dd, J ₁ = 8.0 Hz, J ₂ = 2.4 Hz, 1 H), 7.47 (d, J = 8.0 Hz, 1 H), 4.50–7.05 (m, 2 H), 3.86 (q, J = 6.8 Hz, 1 H), 3.66–3.76 (m, 3 H), 3.36 (dt, J ₁ = 14.8 Hz, J ₂ = 6.0 Hz, 1 H), 2.62–2.75 (m, 2 H), 1.22 (d, J = 7.2 Hz, 3 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 184.7, 160.5, 149.3, 148.6, 139.6, 135.1, 123.9, 111.5, 61.1, 48.8, 45.9, 42.4, 14.8. HRMS (ES+): m/z [M + Na]⁺ calcd for C₁₃H₁₆ ³⁵ClN₅NaO₃: 348.0839; found: 348.0835. HRMS: m/z [M + Na]⁺ calcd for C₁₄H₁₅ ³⁷ClN₅NaO₃: 350.0810; found: 350.0814
• 20 Crystallographic data have been deposited with the accession number CCDC 1410771 at the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: [phone]; e-mail: [e-mail]; website: www.ccdc.cam.ac.uk/conts/retrieving.html.
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