Ugi Reaction
Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 4 569
1H, H on amide group), 9.07-9.13 (m, 1H, H on amide
group). ESI-MS: 521 (MH+).
H on amide group), 8.00 (s, 1H, H on amide group), 9.19 (t,
1H, J ) 5.7 Hz, H on amide group), 9.28 (s, 1H, H on
thiourea). ESI-MS: 480 (MH+).
General Procedure for the Synthesis of Compounds
8d-8i. Resin 5a was shaken in 55% TFA/DCM for 30 min
to remove the Boc group. Following neutralization with 5%
DIEA/DCM, the resin was treated with DIEA (10 equiv)
and corresponding reagents, such as sulfonyl chloride,
isocyanate or thioisocyanate (10 equiv) in anhydrous DMF
overnight. The resin was then washed with DMF (3×) and
DCM (3×), dried and cleaved by HF for 1.5 h at 0 °C. All
samples were purified by preparative HPLC and characterized.
Acknowledgment. The authors would like to thank the
State of Florida Funding, NIH (1R03DA025850-01A1,
Nefzi), NIH (5P41GM081261-03, Houghten), and NIH
(3P41GM079590-03S1, Houghten) for their financial support.
1
Supporting Information Available. H NMR and LC-
MS of all the compounds. This information is available free
1
8d. H NMR (DMSO-d6): δ 1.64-2.40 (m, 11H, H on
piperidine ring and tosyl group), 3.41 (m, 4H, H on
pyrrolidine ring), 4.15 (m, 2H, H on benzyl group), 4.49
(m, 1H, H on pyrrolidine ring), 7.13-7.26 (m, 5H, H on
benzyl group), 7.44 (d, 2H, J ) 8.3 Hz, H on tosyl group),
7.50 (s, 1H, H on amide group), 7.59 (d, 2H, J ) 8.3 Hz, H
on tosyl group), 7.94 (s, 1H, H on amide group), 8.98 (t,
1H, J ) 5.7 Hz, H on amide group). ESI-MS: 499 (MH+).
References and Notes
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1
8e. H NMR (DMSO-d6): δ 1.66-2.28 (m, 8H, H on
piperidine ring), 3.49 (m, 4H, H on pyrrolidine ring), 4.09
(m, 2H, H on benzyl group), 4.49 (m, 1H, H on pyrrolidine
ring), 7.07-7.20 (m, 5 H, H on benzyl group), 7.50 (s, 1H,
H on amide group), 7.69-7.76 (m, 3H, H on naphthalene-
2-ylsulfonyl), 7.94 (s, 1H, H on amide group), 8.08 (d, 1H,
J ) 8.0 Hz, H on naphthalene-2-ylsulfonyl), 8.17 (d, 1H J
) 8.8 Hz, H on naphthalene-2-ylsulfonyl), 8.21 (d, 1H, J )
8.2 Hz, H on naphthalene-2-ylsulfonyl), 8.41 (s, 1H, H on
naphthalene-2-ylsulfonyl), 8.95 (t, 1H, J ) 5.6 Hz, H on
amide group). ESI-MS: 535 (MH+).
1
8f. H NMR (DMSO-d6): δ 1.04 (d, 6H, J ) 6.5, H on
the isopropyl group), 1.58-2.37 (m, 8H, H on piperidine
ring), 3.44 (m, 4H, H on pyrrolidine ring), 3.73 (m, 1H, H
on the isopropyl group), 4.27 (m, 2H, H on benzyl group),
4.51 (m, 1H, H on pyrrolidine ring), 6.86 (s, 1H, H on urea),
7.19-7.30 (m, 5H, H on benzyl group), 7.52 (s, 1H, H on
amide group), 7.96 (s, 1H, H on amide group), 9.09 (t, 1H,
J ) 5.7 Hz, H on amide group). ESI-MS: 430 (MH+).
1
8g. H NMR (DMSO-d6): δ 1.24-2.34 (m, 8H, H on
piperidine ring), 3.58 (m, 4H, H on pyrrolidine ring), 4.29
(m, 2H, H on benzyl group), 4.54 (m, 1H, H on pyrrolidine
ring), 7.20-7.30 (m, 7H, H on benzyl group and phenyl
group), 7.44 (m, 2H, H on phenyl group), 7.53 (s, 1H, H on
amide group), 7.96 (s, 1H, H on amide group), 8.47 (s, 1H,
H on urea), 9.13 (t, 1H, J ) 5.8 Hz, H on amide group).
ESI-MS: 464 (MH+).
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1
8h. H NMR (DMSO-d6): δ 1.08 (t, 3H, J ) 7.2 Hz, H
on ethyl group), 1.23-2.38 (m, 8H, H on piperidine ring),
3.41-3.48 (m, 6H, H on pyrrolidine ring and ethyl group),
4.28 (m, 2H, H on benzyl group), 4.50 (m, 1H, H on
pyrrolidine ring), 6.87 (s, 1H, H on thiourea), 7.19-7.30
(m, 5H, H on benzyl group), 7.54 (s, 1H, H on amide group),
7.97 (s, 1H, H on amide group), 9.15 (t, 1H, J ) 5.7 Hz, H
on amide group). ESI-MS: 432 (MH+).
1
8i. H NMR (DMSO-d6): δ 1.23-2.38 (m, 8H, H on
piperidine ring), 3.50-3.89 (m, 4H, H on pyrrolidine ring),
4.30 (m, 2H, H on benzyl group), 4.56 (m, 1H, H on
pyrrolidine ring), 7.09 (m, 1H, H on benzyl group), 7.28
(m, 9H, H on benzyl group and phenyl group), 7.56 (s, 1H,
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Salvono, J. M.; Chu, V.; Brown, K. D.; Pauls, H. W. Bioorg.