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DOI: 10.1055/s-2004-815414
Solid-Phase Synthesis of N-Alkylated Naltrindoles Using a 3-Nitrobenzyl Safety-Catch Linker
Publication History
Publication Date:
12 January 2004 (online)
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Abstract
We describe an effective solid-phase synthesis of N-substituted naltrindoles using a nitro benzyl safety-catch linker. The linker is stable to both strongly acidic and basic conditions and is cleaved under mildly acidic conditions after conversion of the nitro group to an amide group. Using the linker, a combinatorial synthesis of N-substituted naltrindoles involving the Fischer indole synthesis and N-alkylation was accomplished to provide 16 N-substituted naltrindoles.
Key words
combinatorial chemistry - Fischer indole synthesis - linker - opioid - solid-phase synthesis
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References
Spectra of 5aA: 1H NMR (400 MHz, CD3OD): δ = 0.25-0.42 (2 H, m), 0.57-0.77 (2 H, m), 1.03 (1 H, m), 1.76-1.87 (1 H, m), 2.40-3.60 (9 H, m), 2.73 (1 H, d, J = 15.6 Hz), 5.55 (1 H, d, J = 17.3 Hz), 5.60 (1 H, d, J = 17.3 Hz), 5.65 (1 H, s), 6.62 (1 H, s), 6.62 (1 H, s), 6.96-7.00 (1 H, m), 7.05-7.09 (1 H, m), 7.16-7.29 (6 H, m), 7.43 (1 H, d, J = 7.8 Hz), 8.54 (1 H, s). ESI-MS: 505 (M + H+).
13The ratio was determined by HPLC-MS analysis of crude material using UV absorption at 254 nm.
14Spectra of 5aAA: 1H NMR (400 MHz, CD3OD): δ = 0.33-0.48 (2 H, m), 0.66-0.85 (2 H, m), 1.11 (1 H, m), 1.72-1.87 (1 H, m), 2.55-3.57 (10 H, m), 4.59 (2 H, s), 4.51-4.67 (2 H, m), 5.66 (1 H, s), 6.66 (1 H, s), 6.66 (1 H, s), 6.96-7.12 (9 H, m), 7.21-7.26 (4 H, m), 7.38 (1 H, d, J = 7.8 Hz), 8.53 (2 H, s). ESI-MS: 595 (M + H+).