Please do not adjust margins
Organic & Biomolecular Chemistry
Page 6 of 8
ARTICLE
Journal Name
NMR (CD3CN, 400 MHz, 25 °C): δ 8.36 (br s, 1H), 8.22 (dd, J = 8.5, thanks the National Natural Science Foundation ofVCiehwinAratic(leNOSnFliCne)
DOI: 10.1039/C7OB00253J
1.8, 1H), 8.08 (d, J = 9.0, 2H), 7.88 (d, J = 8.9, 1H), 7.64 (d, J = 8.5, (no. 21202148) for support.
1H), 7.54 (d, J = 2.5, 1H), 7.14 (dd, J = 8.9, 2.5, 1H), 7.12 (d, J =
9.0, 2H), 3.87 (s, 3H), 3.86 (s, 3H), 3.37 (br s, 3H), 1.56 (s, 9H);
19F NMR (CD3CN, 376 MHz, 25 °C): δ -79.30 (s, 1F); 13C NMR
(CD3CN, 100 MHz, 25 °C): δ 187.3, 164.7, 164.7, 162.4, 159.5,
149.3, 139.6, 137.9, 132.7, 124.9, 123.8, 119.2, 118.4, 117.5,
105.6, 56.8, 56.7, 38.5, 28.5, 1.8, 1.6, 1.4, 1.2, 1.0; HRMS: (ESI)
calculated for C27H28IN2O4S [M-(OTf)]+ 603.0809 found
603.0795.
Notes and references
1. V. W. Pike and F. I. Aigbirhio, J. Chem. Soc., Chem. Commun.,
1995, 2215-2216.
2. T. L. Ross, J. Ermert, C. Hocke and H. H. Coenen, J. Am. Chem.
Soc., 2007, 129, 8018-8025.
3. L. Cai, S. Lu and V. W. Pike, Eur. J. Org. Chem., 2008, 2008
,
2853-2873.
4. E. A. Merritt and B. Olofsson, Angew. Chem. Int. Ed., 2009,
48, 9052-9070.
Radiosynthesis methods
5. B. S. Moon, H. S. Kil, J. H. Park, J. S. Kim, J. Park, D. Y. Chi, B.
General procedure. The diaryliodonium salt precursor and
organic solvents for radiosynthesis were stored in an anaerobic
chamber under argon. All organic solvents used were anhydrous
grade, and used as received. The radiofluorinated product was
synthesized by thermolysis of the appropriate diaryliodonium
fluoride using an IBA Synthera® automated synthesizer
equipped with an Integrated Fluidic Processor™ (ABX) and an
automated script, following the steps outlined in Figure S1.
Aqueous [18F]fluoride produced in an IBA Cyclone® 18/9
cyclotron from 97% 18O-enriched water was passed through a
QMA cartridge (pretreated with 1 M sodium bicarbonate (2 mL)
followed by a water (5 mL) rinse) to trap the [18F]fluoride while
the [18O]water passed through to waste. The [18F]fluoride was
eluted from the QMA resin with 620 μL of 4% water in
acetonitrile containing potassium carbonate (0.62 mg) and
Kryptofix [2.2.2] (6.2 mg). The solvent was removed by
azeotropic distillation under argon flow with reduced pressure
and heating to 110 °C for 2.5 min. The diaryliodonium salt
precursor, pre-dissolved in 10% acetonitrile in toluene (1 mL),
was added to the reactor and the mixture was heated for 10 min
to give the product. Identity of the product was confirmed by
comparison of its HPLC trace against a trace of the 19F
compound standard.
C. Lee and S. E. Kim, Org. Biomol. Chem., 2011, 9, 8346-8355.
6. J.-H. Chun and V. W. Pike, Org. Biomol. Chem., 2013, 11
,
6300-6306.
7. N. Ichiishi, A. F. Brooks, J. J. Topczewski, M. E. Rodnick, M. S.
Sanford and P. J. H. Scott, Org. Lett., 2014, 16, 3224-3227.
̅
8. B. Hu, A. L. Vavere, K. D. Neumann, B. L. Shulkin, S. G.
DiMagno and S. E. Snyder, ACS Chem. Neurosci., 2015.
9. W.-J. Kuik, I. P. Kema, A. H. Brouwers, R. Zijlma, K. D.
Neumann, R. A. J. O. Dierckx, S. G. DiMagno and P. H. Elsinga,
J. Nucl. Med., 2015, 56, 106-112.
10. A. Varvoglis, The Organic Chemistry of Polycoordinated
Iodine, Wiley, 1992.
11. J. D. Dunitz, ChemBioChem, 2004, 5, 614-621.
12. B. J. Wang, R. L. Cerny, S. Uppaluri, J. J. Kempinger and S. G.
DiMagno, J. Fluorine Chem., 2010, 131, 1113-1121.
13. B. Wang, L. Qin, K. D. Neumann, S. Uppaluri, R. L. Cerny and
S. G. DiMagno, Org. Lett., 2010, 12, 3352-3355.
14. F. M. Beringer and I. Lillien, J. Am. Chem. Soc., 1960, 82, 725-
731.
15. F. M. Beringer and L. L. Chang, J. Org. Chem., 1972, 37, 1516-
1519.
16. L. Skulski and P. Wroczynski, Bull. Pol. Acad. Sci., Chem.,
1999, 47, 231-238.
17. B. Wang, J. W. Graskemper, L. Qin and S. G. DiMagno,
Angew. Chem. Int. Ed., 2010, 49, 4079-4083.
18. J. W. Graskemper, B. Wang, L. Qin, K. D. Neumann and S. G.
DiMagno, Org. Lett., 2011, 13, 3158-3161.
7-18Fluoro-1-methyl-5-phenyl-1,3-dihydro-2H-benzo[e]
[1,4]diazepin-2-one ([18F]16). According to the general
radiosynthesis procedure, 8 mg of diaryliodonium salt precursor
15 was heated to 140 °C for 10 min to give the product in 32.1
± 4.0% (n=3) radiochemical yield at EOB using TLC followed by
analysis for radioactivity on a Bioscan AR-2000 scanner. HPLC
purification (Zorbax SB-Aq column 3.5 μm 4.6x100 mm, 30%
acetonitrile in pH 2 phosphate buffer, 1 mL/min, 254 nm) gave
the product (30.2 ± 4.7% RCY) in 97% radiochemical purity (t =
34 min).
19. F. M. Beringer, A. Brierley, M. Drexler, E. M. Gindler and C.
C. Lumpkin, J. Am. Chem. Soc., 1953, 75, 2708-2712.
20. Y. Yamada and M. Okawara, Bull. Chem. Soc. Jpn., 1972, 45
,
1860-1863.
21. K. M. Lancer and G. H. Wiegand, J. Org. Chem., 1976, 41
,
3360-3364.
22. M. Tredwell, S. M. Preshlock, N. J. Taylor, S. Gruber, M.
Huiban, J. Passchier, J. Mercier, C. Génicot and V.
Gouverneur, Angew. Chem. Int. Ed., 2014, 53, 7751-7755.
23. A. V. Mossine, A. F. Brooks, K. J. Makaravage, J. M. Miller, N.
Ichiishi, M. S. Sanford and P. J. H. Scott, Org. Lett., 2015, 17
5780-5783.
,
24. K. J. Makaravage, A. F. Brooks, A. V. Mossine, M. S. Sanford
and P. J. H. Scott, Org. Lett., 2016, 18, 5440-5443.
25. L. Qin, B. Hu, K. D. Neumann, E. J. Linstad, K. McCauley, J.
Veness, J. J. Kempinger and S. G. DiMagno, Eur. J. Org.
Chem., 2015, 2015, 5919-5924.
26. A. Krowczynski and L. Skulski, Pol. J. Chem., 1993, 67, 67-70.
27. A. A. M. Mironova, I. I.; Iksanova, S. V.; Orda, V. V.;
Yagupolskii, L. M., Zh. Org. Chem., 1989, 25, 306-311.
28. T. Okuyama and M. Fujita, Acc. Chem. Res., 2005, 38, 679-
686.
2-(4-(N-Boc-3-18fluoro-N-methyl)phenyl)-6-methoxy
benzothiazole ([18F]19). According to the general
radiosynthesis procedure, 4 mg of diaryliodonium salt precursor
18 was heated gradually to 120 °C over the course of 10 min to
give the product in 51.7 ± 1.9% (n=3) radiochemical yield EOB (t
= 27 min), using TLC and HPLC.
29. C. Hansch, A. Leo and R. W. Taft, Chem. Rev., 1991, 91, 165-
195.
Acknowledgements
30. J. D. Andersson and C. Halldin, J. Labelled Compd.
Radiopharm., 2013, 56, 196-206.
Support for this research was provided by NIH R01EB015536
and ALSAC-St. Jude Children's Research Hospital. Bao Hu also
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins