ACS Combinatorial Science
RESEARCH ARTICLE
7.19 (d, 2H, J = 7.5 Hz), 4.69 (m, 1H), 4.60-4.30 (m, 2H), 3.44
(s, 3H), 2.45-2.15 (m, 3H), 1.60-1.40 (m, 2H), 1.31 (s, 12H),
1.40-1.20 (m, 2H), 0.94 (d, 3H, J = 6.5 Hz), 0.89 (t, 3H, J =
7.4 Hz), 0.82 (d, 3H, J = 6.9 Hz).
Chem., Int. Ed. 2002, 41, 2403–2405. (f) Walsh, P. J.; Lurain, A. E.;
Balsells J. Chem. Rev. 2003, 103, 3297–3344. (g) Hua, Z.; Vassar, V. C.;
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Biscoe, M. R.; Buchwald, S. L. J. Am. Chem. Soc. 2008, 130 (41), 13552–
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4319–4328.
(S)-Methyl-2-(N-(biphenyl-4-ylmethyl)pentanamido)-3-methyl-
butanoate 8{3,7,1,7}. Compound 7{3,7,1} (0.37 mmol, 160
mg), bromobenzene (0.44 mmol, 1.491 g mL-1, 46 μL), sodium
carbonate (1.11 mmol, 118 mg), tetrakis(triphenylphosphine)-
palladium(0) (0.01 mmol, 12 mg), toluene (1 mL), EtOH
(1 mL), and water (0.5 mL) were mixed in a microwave vial
and stirred under microwave irradiation at 150 °C for 10 min.
The mixture was cooled to room temperature, diluted with
EtOAc and water, and extracted three times with EtOAc. The
separated organic layer was washed with a saturated sodium
chloride solution, dried over anhydrous magnesium sulfate, fil-
tered, and concentrated under reduced pressure to give a yellow
oil which was purified by chromatography on silica gel, hexane/
EtOAc 8:2, to give 126 mg of the expected product as a pale
yellow oil in 89% yield. 1H NMR mixture of rotamers (CDCl3) δ
(ppm): 7.61-7.52 (m, 3H), 7.52-7.30 (m, 4H), 7.30-7.18 (m,
2H), 4.97 (2d, 1H, J = 10.3 Hz), 4.66 (s, 1.3H), 4.29 (d, 0.3H, J =
15.3 Hz), 4.05 (d, 0.3H, J = 10.9 Hz), 3.45 and 3.36 (2s, 3H),
2.67-2.20 (m, 3H), 1.82-1.54 (m, 2H), 1.50-1.20 (m, 2H),
0.99 (d, 3H, J = 6.5 Hz), 0.95-0.80 (d þ t, 6H, Jd = 7.0 Hz, Jt =
7.3 Hz). 13C NMR mixture of rotamers (CDCl3) δ (ppm):
174.6, 171.2, 140.5, 140.2, 136.4, 128.8, 128.7, 128.1, 127.4,
127.3, 127.0 (2C), 126.8, 126.4, 65.9, 61.8, 51.6, 48.2, 45.4, 33.4,
27.9, 27.4, 22.5, 19.9, 18.8, 13.8. HRMS-ES (m/z) found,
382.2375; calcd for [C24H31O3N1 þ H]þ, 382.2377.
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’ ASSOCIATED CONTENT
Supporting Information. Analytical data (1
H, 13C spec-
S
b
tra, MS, elemental analysis) for compounds are provided, as well
as X-ray crystallography experimental details for 1{2}, 3{1,6},
3{2,10}, 3{3,3}, and 3{3,8}.This material is available free of
’ AUTHOR INFORMATION
Corresponding Author
*Phone: þ44 2083318215. Fax: þ44 2083319805. E-mail:
’ ACKNOWLEDGMENT
Novartis is thanked for funding this work (Ph.D. award to
C.B.). BP is acknowledged for providing funding for a CEM
Explorer microwave reactor. The EPSRC Mass Spectrometry
Unit (Swansea) is thanked for HRMS measurements.
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Bibbins, F.; Meyers, H. V.; Babine, R.; Strickler Bioorg. Med. Chem. Lett.
2006, 16, 5022–5027and references cited therein.
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68, 888–892. (d) Spencer, J.; Rathnam, R. P.; Patel, H.; Nazira, A.
Tetrahedron 2008, 64, 10195–10200.
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dx.doi.org/10.1021/co100011g |ACS Comb. Sci. 2011, 13, 24–31