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zo[d]thiazol-2-yl)-2H-chromen-2-one (11). (1R,8S,9S)-Bicyclo-
[6.1.0]non-4-yn-9-ylmethanol (11 mg, 0.076 mmol) and compound
6 were combined in a round-bottom flask. Dry MeCN (3 mL) was
added under and the resulting solution was stirred at 368C under
nitrogen atmosphere. After 2 h of stirring, TLC analysis indicated
that all of the starting materials have been consumed. The solvent
was evaporated. The ethanolic solution of the residue (2 mL EtOH)
was added dropwise to a stirring mixture of compound 9 (12 mg,
0.07 mmol) and piperidine (2 mL). After 20 min of stirring at reflux
temperature, the precipitate was filtered, washed repeatedly with
cold ethanol and dried in vacuum. Yellow powder 75%.Rf =0.5
(Hexanes/EtOAc 1:3 v/v). 1H NMR (500 MHz, DMSO): d=9.19 (1H,
s), 8.34 (1H, s), 8.17 (1H, d, J=8.4 Hz), 8.05 (1H, d, J=8.2 Hz), 7.62
(2H, d, J=8.0 Hz), 7.17 (1H, d, J=7.9 Hz), 4.28 (2H, s), 3.48 (4H, s),
3.06 (2H, s), 2.89 (3H, dd, J=31.9 Hz, 12.4), 2.73–2.56 (2H, m),
2.25–1.91 (3H, m), 1.60 (4H, d, J=8.5 Hz), 1.07–0.93 (2H, m),
0.88 ppm (3H, s); 13C NMR (126 MHz, DMSO): d=162.7, 159.7,
155.0, 152.5, 145.9, 144.6, 142.5, 137.0, 135.1, 133.6, 132.4, 125.1,
123.4, 120.4, 118.1, 117.2, 116.3, 109.1, 107.1, 57.8, 25.9, 23.7, 22.5,
21.4, 19.4, 18.9 ppm; LC-MS (ESI): tret =1.79 min, m/z calcd: 512.14
[M+H]+; found: 512.00; HRMS (ESI+, MeCN): m/z calcd for
C26H21N7O3SNa: 534.1324 [M+Na]+; found: 534.1319.
found: 320.65; HRMS (ESI+, MeCN): m/z calcd for C16H8N4O2SNa:
343.0266 [M+Na]+; found: 343.0265.
3-(6-Aminobenzo[d]thiazol-2-yl)-2H-chromen-2-one (14b): Com-
pound 4 (300 mg, 1.12 mmol) was suspended in ethanol (10 mL)
and piperidine (3 mL) was added. Distilled salicylaldehyde (120 mL,
1.12 mmol) was mixed in dropwise, and the resulting yellow sus-
pension was stirred at reflux temperature for 1 hour followed by
filtration. Dye precursor 14a was obtained as yellow, highly insolu-
ble precipitate which was filtered, washed repeatedly with diethyl
ether and dried in vacuo (41%). Subsequently, finely powdered
14a (80 mg, 0.24 mmol) was suspended in ethanol (20 mL) and
SnCl2 dihydrate (178 mg, 1.23 mmol) and cc HCl (1500 mL) were
added. The resulting suspension was stirred at reflux temperature
for 1.5 h. The cold reaction mixture was poured onto water and
with slow, careful addition of NaOH (10%) the pH of the solution
was adjusted between 6.5 and 7. The aqueous phase was washed
with ethyl acetate (330 mL). The volatiles were evaporated and
the crude product was purified (column chromatography, silica,
CH2Cl2 with 1–10% methanol) to yield title compound 14b as vivid
red powder (32%). Rf =0.35 (CH2Cl2/Methanol 20:1 v/v); 1H NMR
(500 MHz, DMSO): d=9.03 (s, 1H), 8.00 (d, J=6.6 Hz, 1H), 7.73 (d,
J=8.7 Hz, 1H), 7.71–7.65 (m, 1H), 7.50 (d, J=8.3 Hz, 1H), 7.46–7.39
(m, 1H), 7.12 (d, J=1.8 Hz, 1H), 6.86 (dd, J=8.7, 2.1 Hz, 1H),
5.60 ppm (s, 2H); 13C NMR (126 MHz, DMSO): d=174.64, 159.81,
153.42, 147.88, 144.59, 139.97, 138.68, 133.26, 130.18, 125.55,
123.51, 120.45, 119.53, 116.57, 116.36, 103.50 ppm; LC-MS (ESI):
3-(6-Azidobenzo[d]thiazol-2-yl)-7-((5aS,6R,6aR)-6-(hydroxymeth-
yl)-5,5a,6,6a,7,8-hexahydrocyclopropa[5,6]cycloocta[1,2-d]
[1,2,3]triazol-1(4H)-yl)-2H-chromen-2-one (12): (1R,8S,9S)-Bicy-
clo[6.1.0]non-4-yn-9-ylmethanol (20 mg, 0.133 mmol) and com-
pound 9 (24 mg, 0,146 mmol) were combined in a round-bottom
flask. Dry MeCN (3 mL) was added and the resulting solution was
stirred at 368C under nitrogen atmosphere. After 2 h of stirring,
TLC analysis showed that all of the starting materials have been
consumed. The solvent was evaporated and the ethanolic solution
of the residue (3 mL EtOH) was added dropwise to a stirring mix-
ture of compound 6 (17 mg, 0.063 mmol) and piperidine (2 mL).
After 20 min of stirring at reflux temperature, the precipitate was
filtered, washed repeatedly with cold ethanol and dried in vacuum.
Yellow powder, 71%. Rf =0.5 (Hexanes/EtOAc 1:3 v/v).1H NMR
(500 MHz, DMSO): d=9.19 (1H, s), 8.34 (1H, s), 8.17 (1H, d, J=
8.4 Hz), 8.05 (1H, d, J=8.2 Hz), 7.62 (2H, d, J=8.0 Hz), 7.24 (1H, s),
7.17 (1H, d, J=8.0 Hz), 4.28 (2H, s), 3.48 (4H, s), 3.06 (2H, s), 2.89
(3H, dd, J=31.9 Hz, 12.4), 2.73–2.59 (2H, m), 2.08 (3H, d, J=
22.1 Hz), 1.61 (4H, s), 1.05–0.94 (2H, m), 0.88 ppm (3H, s);13C NMR
(126 MHz, DMSO): d=159.8, 159.5, 153.8, 150.0, 145.0, 139.9,
138.21, 135.20, 131.68, 122.77, 120.69, 119.89, 113.82, 112.71,
110.00, 57.80, 31.51, 25.80, 23.84, 23.24, 22.40, 21.84, 21.34, 20.82,
19.39, 18.70 ppm; LC-MS (ESI): tret =1.85 min, m/z calcd: 512.14
[M+H]+; found: 512.00; HRMS (ESI+, MeCN): m/z calcd for
C26H21N7O3SNa: 534.1324 [M+Na]+; found: 534.1319.
t
ret =2.20 min, m/z calcd: 295.05 [M+H]+; found: 294.65; HRMS
(ESI+, MeCN): m/z calcd for C16H10N2O2SNa: 317.0361 [M+Na]+;
found: 317.0357.
3-(6-Azidobenzo[d]thiazol-2-yl)-2H-chromen-2-one (14): Amine
14b (30 mg, 0.10 mmol) was suspended in cold 6m HCl (2 mL) and
methanol was added until a clear solution was obtained. Aqueous
NaNO2 solution (8 mg, 0.11 mmol in 500 mL) was added dropwise
while the temperature was maintained around 08C, followed by
30 min of stirring at 08C. NaN3 (10 mg, 0.15 mmol) in 1 mL water
was added. The ice bath was removed and after 3 h of stirring at
room temperature the resulting precipitate was filtered, dissolved
in ethyl acetate and washed with brine. Target monoazide 14 was
obtained as yellow powder (34%); Rf =0.8 (Hexanes/EtOAc 3:1 v/
1
v). H NMR (400 MHz, DMSO): d=9.21 (s, 1H), 8.09 (s, 1H), 8.07 (s,
1H), 8.02 (d, J=2.2 Hz, 1H), 7.76 (t, J=7.7 Hz, 1H), 7.62–7.41 (m,
1H), 7.30 ppm (dd, J=8.7, 2.0 Hz, 1H); 13C NMR (101 MHz, DMSO):
d=159.58, 159.41, 153.32, 149.53, 141.80, 137.60, 136.96, 133.66,
130.22, 125.22, 123.66, 119.30, 118.92, 118.81, 116.24, 112.17 ppm;
LC-MS (ESI): tret =3.50 min, m/z calcd 321.04 [M+H]+; found:
320.65; HRMS (ESI+, MeCN): m/z calcd for C16H8N4O2SNa: 343.0266
[M+Na]+; found: 343.0265.
7-Azido-3-(benzo[d]thiazol-2-yl)-2H-chromen-2-one (13): Ethyl
1,3-benzothiazol-2-ylacetate (50 mg, 0.22 mmol) prepared accord-
ing to literature[22] was dissolved in ethanol (3 mL) and catalytic
amount of piperidine was added (3 mL). The color of the solution
turned orange. Compound 9 (36 mg, 0.22 mmol) was added por-
tionwise and the resulting suspension was stirred for 1 hour at
708C. A bright-orange precipitate was formed, which was filtered,
washed with cold ethanol and dried in vacuo (57%). Rf =0.8 (Hex-
anes/EtOAc 3:1 v/v); 1H NMR (400 MHz, DMSO): d=9.24 (s, 1H),
8.19 (d, J=7.9 Hz, 1H), 8.10 (dd, J=11.3, 8.4 Hz, 2H), 7.59 (t, J=
7.6 Hz, 1H), 7.49 (t, J=7.5 Hz, 1H), 7.35 (d, J=1.5 Hz, 1H),
7.25 ppm (dd, J=8.4, 1.9 Hz, 1H); 13C NMR (101 MHz, DMSO): d=
159.79, 159.26, 154.53, 151.93, 145.15, 141.61, 135.83, 133.22,
131.77, 126.67, 125.37, 122.43, 122.23, 117.94, 116.74, 115.99,
106.64 ppm; LC-MS (ESI): tret =3.50 min, m/z calcd 321.04 [M+H]+;
Acknowledgements
Financial support of the Hungarian Academy of Sciences
(LP2013-55/2013 and LP2013-64/2013) and the Hungarian
Scientific Research Fund (NN-110214, NN-116265, K-104045,
K-108752) is greatly acknowledged.
Keywords: cycloaddition · click chemistry · dyes/pigments ·
fluorescent probes · peptides
Chem. Eur. J. 2016, 22, 6382 – 6388
6387
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim