Paper
Organic & Biomolecular Chemistry
(
m, 2H), 5.34 (s, 2H), 4.34 (t, 2H, J = 6.3), 4.01 (s, 2H), 3.90 (s,
Acknowledgements
4
H), 3.35–3.24 (m, 2H), 2.17–2.04 (m, 2H), 1.62–1.49 (m, 2H).
1
3
3
C NMR (101 MHz, CDCl ) δ 163.3, 162.7, 159.0, 149.0, 145.1, We acknowledge the EPSRC National Mass Spectrometry
1
1
1
5
43.3, 138.4, 136.7, 135.1 (d, J = 2.8), 133.4 (d, J = 10.0), 132.3, Service, University of Wales, Swansea for the provision of high-
31.0, 130.5 (d, J = 12.6), 129.9, 129.0, 128.4, 126.3, 125.8, resolution mass spectrometry. DFT calculations were per-
23.6, 123.5, 123.4, 123.3, 122.6, 122.2, 117.8 (d, J = 85.8), 59.8, formed on the QMUL Apocrita facility. LF is grateful to the
3
1
3.5, 48.6, 35.5, 29.9 (d, J = 17.3), 21.1 (d, J = 53.5), 19.2.
P
Chinese Scholarship Council for the provision of a PhD
1
9
NMR (162 MHz, CDCl ) δ 23.91. F NMR (377 MHz, CDCl ) δ studentship.
−
3
−
3
1
151.75. IR: (νmax/cm ) 3067, 1738, 1585, 1436, 1366, 1232,
+
1
4
112, 1037, 785, 689. HR-NSI MS (m/z) [M − BF ] calcd for
C H N O P 873.3537, found 873.3544.
5
2
46 10 2
Notes and references
2
-(1-((6-(4-((Bis(pyridin-2-ylmethyl)amino)methyl)-1H-1,2,3-
1
S. L. Sensi, P. Paoletti, A. I. Bush and I. Sekler, Nat. Rev.
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triazol-1-yl)-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)methyl)-
1H-1,2,3-triazol-4-yl)-N-(2-(dimethylamino)ethyl)acetamide (9)
2
1
(92.4 mg, 90%, M.p. 113–117 °C). H NMR (400 MHz, CDCl ) δ
3
8.71–7.64 (m, 2H), 8.53 (d, 2H, J = 4.7), 8.26 (d, 1H, J = 8.6),
8.17 (s, 1H), 7.86 (s, 1H), 7.83–7.76 (m, 2H), 7.70–7.63 (m, 2H),
7.59 (d, 2H, J = 7.8), 7.18–7.12 (m, 2H), 6.70–6.58 (bs, 1H), 5.52
3 A. S. Prasad, Mol. Med., 2008, 14, 353–357.
4 P. Bonaventura, G. Benedetti, F. Albarède and P. Miossec,
Autoimmun. Rev., 2015, 14, 277–285.
(
2
s, 2H), 5.00 (s, 2H), 4.06 (s, 2H), 3.94 (s, 4H), 3.32–3.23 (m,
H), 2.34 (t, 2H, J = 6.1), 2.13 (s, 6H). C NMR (101 MHz,
5 R. K. Blanchard, J. B. Moore, C. L. Green and R. J. Cousins,
Proc. Natl. Acad. Sci. U. S. A., 2002, 98, 13507–13513.
6 K. A. Jackson, R. A. Valentine, L. J. Coneyworth, J. C. Mathers
and D. Ford, Biochem. Soc. Trans., 2008, 36, 1262–1266.
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D. N. Johnson, A. A. Giangreco, E. Martens-Uzunova,
O. Bagasra, A. Kajdacsy-Balla and L. Nonn, J. Biol. Chem.,
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1
3
CDCl ) δ 165.1, 163.3, 162.8, 159.0, 149.2, 145.0, 143.6, 138.5,
3
1
1
4
1
36.6, 132.4, 131.0, 130.0, 129.1, 128.5, 126.3, 125.7, 125.1,
23.4 (overlapping signals), 122.6, 122.2, 59.8, 57.4, 52.9, 48.5,
−
1
5.0, 37.2, 35.4. IR: (νmax/cm ) 3128, 1610, 1551, 1473, 1428,
+
366, 1231, 1038, 810, 782. HR-NSI MS (m/z) [M + H] calcd for
C H N O 685.3106, found 685.3104.
3
6
37 12 3
6
-(4-((Bis(pyridin-2-ylmethyl)amino)methyl)-1H-1,2,3-triazol-1-
yl)-2-ethyl-1H-benzo[de]isoquinoline-1,3(2H)-dione (10)
1
0 L. Y. Fong, R. Jing, K. J. Smalley, Z.-X. Wang, C. Taccioli,
S. Fan, H. Chen, H. Alder, K. Huebner, J. L. Farber,
O. Fiehn and C. M. Croce, Proc. Natl. Acad. Sci. U. S. A.,
Under a nitrogen atmosphere, 4-azido-N-ethyl-1,8-naphthali-
mide S5 (0.160 g, 0.62 mmol) and alkyne 2 (0.150 g,
0
.62 mmol) were dissolved in a mixture of NMP (6.2 mL) and
2018, 115, E11091–E11100.
EtOH (6.2 mL). To this mixture tetrakis(acetonitrile)copper(I)
hexafluorophosphate (45.0 mg, 0.12 mmol) was added and
stirred at room temperature for 24 hours. After the reaction
1
1
1
1
1 Q. Sun, R. M. Van Dam, W. C. Willett and F. B. Hu,
Diabetes Care, 2009, 32, 629–634.
2 C. W. Shuttleworth and J. H. Weiss, Trends Pharmacol. Sci.,
3 2
was complete, saturated EDTA in 17% NH ·H O (20.0 mL) was
2
011, 32, 480–486.
3 S. J. Lippard and E. Tomat, Curr. Opin. Chem. Biol., 2010,
4, 225–230.
poured into the mixture and the precipitate that formed was
collected by filtration, then washed with water (30.0 mL). This
crude product was purified by flash chromatography (eluent:
1
4 Q. Lu, H. Haragopal, K. G. Slepchenko, C. Stork and
Y. V. Li, Int. J. Physiol., Pathophysiol. Pharmacol., 2016, 8,
DCM/MeOH 20 : 1) to give 10 (0.290 g, 93%, M.p. 93–97 °C) as
1
a brown solid. H NMR (400 MHz, CDCl
3
) δ 8.67–8.60 (m, 2H),
35–43.
8
1
7
4
1
1
5
1
.48 (dd, 2H, J = 4.9, 0.8), 8.19 (dd, 1H, J = 8.6, 1.0), 8.11 (s,
1
5 C. D. Ellis, F. Wang, C. W. MacDiarmid, S. Clark, T. Lyons
and D. J. Eide, J. Cell Biol., 2004, 166, 325–335.
H), 7.78–7.71 (m, 2H), 7.65–7.58 (m, 2H), 7.54 (d, 2H, J = 7.8),
.13–7.07 (m, 2H), 4.20 (q, 2H, J = 7.1), 4.01 (s, 2H), 3.89 (s,
1
3
16 M.-H. Kim, T. B. Aydemir, J. Kim and R. J. Cousins, Proc.
Natl. Acad. Sci. U. S. A., 2017, 114, E5805–E5814.
3
H), 1.29 (t, 3H, J = 7.1). C NMR (101 MHz, CDCl ) δ 163.4,
62.9, 158.9, 149.1, 144.9, 138.2, 136.6, 132.0, 130.6, 129.5,
28.9, 128.5, 126.3, 125.7, 125.5, 123.7, 123.4, 122.9, 122.2,
1
7 B. H. Bin, J. Bhin, J. Seo, S. Y. Kim, E. Lee, K. Park,
D. H. Choi, T. Takagishi, T. Hara, D. Hwang, H. Koseki,
Y. Asada, S. Shimoda, K. Mishima and T. Fukada, J. Invest.
Dermatol., 2017, 137, 1682–1691.
−
1
9.8, 48.4, 35.7, 13.3. IR: (νmax/cm ) 3196, 1703, 1611, 1551,
473, 1427, 1365, 1230, 1119, 1037, 950, 726. HR-NSI MS (m/z)
+
[M + H] calcd for C29
H
26
N
7
O
2
504.2142, found 504.2134.
1
8 S. L. Sensi, D. Ton-That, P. G. Sullivan, E. A. Jonas,
K. R. Gee, L. K. Kaczmarek and J. H. Weiss, Proc. Natl.
Acad. Sci. U. S. A., 2003, 100, 6157–6162.
Conflicts of interest
19 A. Atkinson, O. Khalimonchuk, P. Smith, H. Sabic, D. Eide
and D. R. Winge, J. Biol. Chem., 2010, 285, 19450–19459.
There are no conflicts to declare.
10018 | Org. Biomol. Chem., 2019, 17, 10013–10019
This journal is © The Royal Society of Chemistry 2019