F
N. A. Lengkeek et al.
150.42, 156.68, 157.05, 163.80 (d, 1JCF 250), 171.39, 171.59. dF
(CDCl3, 376.50 MHz) ꢀ76.79 (s, CF3COꢀ2 ), ꢀ104.28 (s, Ar-F).
m/z 432.01 ([M ꢀ NHC-4-fluorobenzenesulfonamide]þ, 632.01
([M þ H]þ), 654.98 ([M þ Na]þ) HR-MS m/z 632.2380;calcd for
[C33H35FN5O5S]þ 632.2337.
13.3 mg). Examination of the peaks by HPLC revealed fraction
1 still contained two compounds, while fraction 2 contained a
single product. Further attempts to purify fraction 1 using a
range of HPLC modifiers was not successful. 1H NMR analysis
revealed fraction 2 contained the desired compound (13.3 mg,
0.02 mmol, 28 %). dH (CD3CN, 400.13 MHz) 1.42 (m, 2H), 1.66
(m, 2H), 2.09 (m, 2H), 2.99 (m, 2H), 3.09 (m, 1H), 4.19 (m, 2H),
4.36 (m, 1H), 4.51 (dt, J1 47.13, J2 6.06, 2H), 5.00 (s, 1H), 6.13
(br, 2H), 6.72 (AB doublet, 2H, J 8.47), 7.04 (AB doublet, 2H,
J 8.47), 7.07 (br, 2H), 7.20–7.37 (m, 10H). dC (CD3CN,
100.61 MHz) 14.52, 26.38 (d, J 20.12), 30.09, 30.35, 43.04,
50.78 (d, J 5.03), 53.96, 58.40, 83.40 (d, J 163.01) 116.12,
127.95, 128.00, 129.45, 129.47, 129.72, 131.14, 141.00, 141.11,
156.98, 158.23, 172.31, 172.79. dF (CD3CN, 376.50 MHz)
ꢀ76.38 (s, CF3COꢀ2 ), ꢀ222.18 (s, ꢀCH2F). m/z (ꢀve) 596.05
([MI ꢀ H]ꢀ, 632.03 ([MI þ Cl]ꢀ, 710.06 ([MI þ CF3CO2]ꢀ);
(þve) 620.01 ([MI þ Na]þ) (MI ¼ 597.24, C30H36FN5O5S).
HR-MS m/z 589.2524; calcd for [C30H37N5O5FS]þ 589.2499.
Nv-(3-Cyano-4-fluorobenzenesulfonyl)BIBP3226 (9c)
4-Fluoro-3-cyano-benzenesulfonyl
chloride
(41.6 mg,
0.19mmol, 1.2 equiv.) was added to a stirred suspension of 4
(100mg, 0.16 mmol, 1 equiv.) and Et3N (34 mL, 0.24 mmol, 1.5
eq) in CH3CN (2 mL). The reaction mixture was stirred under
nitrogen at r.t. for 20 h and then evaporated to dryness. TFA and
CH2Cl2 (1/4, v/v, 5 mL) wereaddedtothe residue and the mixture
stirred at 408C for 20 h. The reaction mixture was evaporated to
dryness and re-evaporated with CH2Cl2 (3ꢁ 5 mL) to remove
residual TFA. The crude product was purified by flash chroma-
tography (eluent: 0–20 % CH3OH/EtOAc) and the eluent evapo-
rated to dryness. This material was further purified by preparative
HPLC employing an isocratic solvent system (60 % CH3CN/
30% H2O/10 % (1% TFA in H2O)) on a Grace Alltima C8
column (10mm, 250mm ꢁ 22 mm). One fraction was collected
(5.2–5.6 min). Saturated aqueous NaHCO3 was added to the
eluate containing the product (tR ¼ 5.2–5.6 min) to reach pH 8,
and the solution was concentrated under pressure to ,20 mL and
then washed with EtOAc and CH2Cl2 (2ꢁ 20 mL, each). The
organic phases were combined and dried over anhydrous
Na2SO4, filtered, and evaporated to dryness to yield the product
as a white solid (13 mg, 0.02 mmol, 12 %). dH (d6-DMSO,
400.13 MHz,) 1.35–1.48 (m, 2H), 1.48–1.67 (m, 2H), 3.05
(m, 2H), 4.14 (m, 2H), 4.32 (m, 1H), 5.11 (s, 1H), 6.67 (AB
doublet, 2H, J 8.50), 6.99 (AB doublet, 2H, J 8.50), 7.31–7.18
(m, 10H), 7.60 (app t, 1H, J 9.00), 8.16 (m, 1H), 8.29 (m, 2H),
8.39 (app d, 1H, J 8.08), 9.24 (s, 1H). dC (d6-DMSO,
Supplementary Material
Additional synthesis details and biological evaluation of the
compounds are available on the Journal’s website.
Acknowledgements
The authors gratefully acknowledge the Cooperative Research Centre for
Biomedical Imaging Development (CRCBID) for financial support. They
thank Cathy Jiang and Iveta Kurlapski for technical assistance.
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Under an atmosphere of N2(g), 8 (52.3 mg, 0.08 mmol) was
dissolved in dry CH3CN (3 mL) and cooled in a salt–ice bath
before Et3N (35 mL, 0.48 mmol) and 3-fluoropropylsulfonyl
chloride (13 mL, 0.112 mmol) were added via syringe. The
mixture was allowed to warm to r.t. over 20 h. The mixture
was taken to dryness and the residue redissolved in fresh CH3CN
(4 mL) and TFA (0.5 mL) before being heated at reflux for 20 h.
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purification was achieved using preparative HPLC employing
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in H2O) on a Grace Altima C18 semi-preparative column
(10 ꢁ 250 mm, 10mM). Two major peaks were collected: frac-
tion 1 (12–13.5 min, 0.2 mg) and fraction 2 (15–16 min,
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