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Synlett 2004(12): 2165-2166  
DOI: 10.1055/s-2004-831308
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Short, Novel Approach to 2,3,4a,5-Tetrahydro-1H-pyrazino[1,2-a]quinoline-4,6-diones

Ronald C. Bernotas*a,
Aventis Pharmaceuticals, Box 6800, Route 202-206, Bridgewater, NJ 08807, USA
Fax: +1(484)8659399; e-Mail: bernotr@wyeth.com;
Further Information

Publication History

Received 4 May 2004
Publication Date:
26 August 2004 (online)

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A Short, Novel Approach to 2,3,4a,5-Tetrahydro-1H-pyrazino[1,2-a]quinoline-4,6-dionesSynlett 2004; 2004(14): 2646-2646
DOI: 10.1055/s-2004-834814

Abstract

An expeditious route to constrained arylpiperazinones has been developed. The key reaction formed the tricyclic system in one-pot via a 1,4-addition-lactamization-aromatic substitution sequence. Four examples were prepared.

Key words

1,4-additions - nucleophilic aromatic substitutions - cyclizations - lactams - medicinal chemistry

    References

  • 1 Current address: R. C. Bernotas, Wyeth Pharmaceuticals, 500 Arcola Road, Collegeville, PA 19426, USA
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8

All compounds gave satisfactory spectral data (1H NMR, 13C NMR, and 19F NMR, IR, and CI-MS). Spectral data for representative compounds: 10a (gradually decomposes in CDCl3): 1H NMR (CDCl3): δ = 7.59 (1 H, dt, J = 2.0, 7.9 Hz), 7.29 (1 H, m), 7.15 (1 H, t, J = 7.9 Hz), 7.04 (1 H, t, J = 8.9 Hz), 5.80 (1 H, s), 4.20 (2 H, q, J = 7.1 Hz), 1.31 (3 H, t, J = 7.1 Hz) ppm. 13C NMR (CDCl3): δ = 159.8 (d, J = 249 Hz, F-coupled), 153.4, 130.6 (d, J = 9.0 Hz), 128.4 (d), 126.1 (d, J = 13.0 Hz, F-coupled), 124.5, 115.6 (d, J = 21.0 Hz, F-coupled), 85.4, 77.3, 62.3, 58.3, 13.91 ppm. 19F NMR (CDCl3): δ = -118.1 ppm. MS (CI/CH4): m/z (%) = 223 (30) [M + H], 205 (100) [M + H - H2O]. IR: 1712, 1613, 1589 cm-1. Compound 11a: 1H NMR (CDCl3): δ = 7.81 (1 H, dt, J = 2.0, 8.9 Hz), 7.74 (1 H, dd, J = 3.3, 15.6 Hz), 7.57 (1 H, m), 7.25 (1 H, t, J = 7.9 Hz), 7.15 (1 H, dd, J = 8.9, 10.9 Hz), 6.83 (1 H, dd, J = 2.0, 8.9 Hz), 4.30 (2 H, q, J = 7.1 Hz), 1.35 (3 H, t, J = 7.1 Hz) ppm. 13C NMR (CDCl3): δ = 188.1, 165.4, 163.4, 160.0, 139.1 (d), 135.2 (d), 131.6 (d, J = 48 Hz, F-coupled), 125.6 (d, J = 6.0 Hz, F-coupled), 124.7, 116.7 (d, J = 22.0 Hz, F-coupled), 61.3, 14.1 ppm. 19F NMR (CDCl3): δ = -109.2 ppm. MS (APCI): m/z (%) = 223 (100) [M + H]. IR: 1724, 1672, 1610 cm-1. Compound 5a: 1H NMR (DMSO-d 6): δ = 8.18 (1 H, br s), 7.75 (1 H, d, J = 7.8 Hz), 7.50 (1 H, t, J = 7.8 Hz), 7.15 (1 H, d, J = 8.0 Hz), 6.85 (1 H, t, J = 7.8 Hz), 4.13 (1 H, br d), 4.06 (1 H, dd, J = 4.9, 12.8 Hz), 3.43 (1 H, app dt, J = 5.9, 11.8 Hz), 3.30 (1 H, br d), 3.10 (1 H, app dt, J = 4.0, 11.4 Hz), 2.91 (1 H, dd, J = 4.9, 16.8 Hz), 2.76 (1 H, dd, J = 12.8, 16.7 Hz) ppm. 13C NMR (DMSO-d 6): δ = 192.1, 167.8, 151.3, 135.6, 127.3, 120.3, 118.2, 114.3, 58.3, 42.1, 39.9, 39.2 (partly obscured by DMSO pattern) ppm. MS (APCI): 217 (100) [M + H]. IR: 1723, 1679, 1623 cm-1.