Full Paper
2
,2-(Boc)-aminoethoxy-ethanol-N-(quinol-8-yl)acetamide
Experimental Section
(
Boc=tert-butyloxycarbonyl) (3)
General procedures
Compound 2 (590 mg, 2.04 mmol), Boc O (534 mg, 2.45 mmol) and
2
NMR spectra were recorded using a Bruker Avance DRX 400 spec-
trometer. Chemical shifts are reported in ppm with solvent as inter-
nal reference. Electronic absorption spectra were recorded using
a PerkinElmer UV/Vis spectrometer.
Et N (0.28 mL, 2.04 mmol) were stirred in CH Cl (60 mL) for 12 h.
3
2
2
The reaction was monitored by means of TLC and concentrated
under reduced pressure and purified by means of column chroma-
1
tography (CH Cl –MeOH) as a yellow solid (850 mg, 90%). H NMR
2
2
(
CDCl3): d=10.37 (br, 1H; NH), 8.70 (br, 2H; NHCCHCHCH,
3
NCHCHCH), 8.20 (d, J(H,H)=7.7 Hz, 1H; NHCCHCHCH), 7.57–7.48
m, 3H; NCHCHCH, NHCCHCHCH, NCHCHCH), 4.23 (m, 2H), 3.77–
3.46 (m, 8H; NCH CH O, OCH CH OH), 1.45 ppm (s, 9H; (CH ) );
Materials
(
Solvents and starting materials were obtained from Aldrich, Fluka,
Acros and Alfa. They were used without further purification unless
2
2
2
2
3 3
1
3
C NMR (CDCl ): d=169.0 (CO), 155.3 (CO), 148.4 (NHCCHCHCH),
3
otherwise stated. Water and H O refer to high-purity water with
138.5 (NHCCN), 136.3 (NCHCHCH), 134.1 (NHCCCCH), 128.0
(NHCCHCHCH), 127.4 (NCHCHCH), 121.9 (NHCCHCHCH), 121.7
(NCHCHCH), 116.6 (NHCCHCHCH), 81.3 (OC(CH ) ), 72.5 (COCH NH),
2
1
ꢀ
a resistivity value of 18 MWcm obtained from the Millipore/MilliQ
purification system. Lanthanide chloride salts were purchased from
Aldrich. The precise metal ion content was determined by colori-
metric titration in acetate buffer (pH 4.5) using a standardised
H Na EDTA (EDTA=ethylenediaminetetraacetic acid) solution
3
3
2
70.3 (OCH CH OH), 61.7 (OCH CH OH), 54.0 (NHCH CH O), 48.5
2
2
2
2
2
2
(NHCH CH O), 28.2 ppm ((CH ) ); IR: n˜ =3326 (OH and NH stretch),
2
2
3 3
2
2
1682 (C=O), 1457 (CH ), 1392 (CH ), 1246 (CꢀO), 1165 (CꢀO),
3
3
ꢀ
1
+
+
(
Merck) and Xylenol Orange as indicator.
1136 cm (CꢀO); MS (ESI+): m/z: 390 [M+H] , 412 [M+Na] .
2-Chloro-N-(quinol-8-yl)acetamide (1)
2,2-(Boc)-aminoethoxy-ethyl-methanesulfonate-N-(quinol-8-
yl)acetamide (4)
2
-Chloroacetyl chloride (1.3 mL, 16.6 mmol) dissolved in chloroform
(
30 mL) was added dropwise to a cooled solution of 8-aminoquino-
Compound 3 (395 mg, 1.01 mmol) was dissolved in CH Cl (50 mL)
2
2
line (2.00 g, 13.9 mmol), pyridine (1.6 mL, 19.4 mmol) and chloro-
form (90 mL) over a period of 1 h. After stirring for 2 h at room
temperature, the mixture was concentrated under reduced pres-
sure and the resultant red-brown solid purified by silica gel
and cooled to 08C. Triethylamine (0.42 mL, 3.04 mmol) and metha-
nesulfonyl chloride (0.20 mL, 2.53 mmol) were then added drop-
wise over 20 min. Following the complete addition of the reagents,
the reaction mixture was stirred for a further 10 min and then at
room temperature for 1 h. The reaction was monitored by means
of TLC, and purified by means of column chromatography (CH Cl –
column chromatography using dichloromethane to give the prod-
1
uct as an off-white solid (2.02 g, 79%). H NMR (CDCl ): d=10.94
3
2
2
3
1
(
(
br, 1H; NH), 8.89 (dd, J(H,H)=4.2, 4.2 Hz, 1H; NHCCHCHCH), 8.78
dd, J(H,H)=4.2, 4.2 Hz, 1H; NCHCHCH), 8.21 (dd, J(H,H)=8.0,
MeOH), 450 mg, 90%. H NMR (CDCl ): d=10.36 (br, 1H; NH), 8.70
3
3
3
3
(br, 2H; NHCCHCHCH, NCHCHCH), 8.20 (d, J(H,H)=7.7 Hz, 1H;
4
7
.2 Hz, 1H; NHCCHCHCH), 7.59 (m, 2H; NHCCHCHCH, NCHCHCH),
NHCCHCHCH), 7.57–7.48 (m, 3H; NCHCHCH, NHCCHCHCH,
NCHCHCH), 4.15–4.27 (m, 4H), 3.76–3.60 (m, 6H), 2.97 (s, 3H;
3
.51 (q, J(H,H)=4.2 Hz, 1H; NCHCHCH), 4.34 ppm (s, 2H; CH2);
1
3
13
C NMR (CDCl3): d=164.5 (CO), 148.5 (NHCCHCHCH), 136.6
SO CH ), 1.45 ppm (s, 9H; (CH ) ); C NMR (CDCl ): d=168.5 (CO),
2
3
3 3
3
(
(
(
(
NCHCHCH), 133.5 (NHCCCCH), 128.0 (NHCCHCHCH), 127.3
NCHCHCH), 122.6 (NHCCHCHCH), 121.8 (NCHCHCH), 117.0
155.2 (CO), 148.4 (NHCCHCHCH), 136.3 (NCHCHCH), 134.1
(NHCCCCH), 128.00 (NHCCHCHCH), 127.4 (NCHCHCH), 121.8
(NHCCHCHCH), 116.4 (NHCCHCHCH), 81.3 (OC(CH3)3), 70.4
(OCH CH OH), 68.7 (OCH CH OH), 54.6 (NHCH CH O), 48.6
NHCCHCHCH), 43.4 ppm (CH Cl); IR: n˜ =3325 (NH stretch), 1669
2
ꢀ1
C=O), 1592 (NH bend), 1328 (CꢀN), 827 cm (CꢀCl); LC/MS: m/z:
2
2
2
2
2
2
+
2
21 [M+H] .
(NHCH CH O), 37.4 (SO CH ), 28.2 ppm ((CH ) ); IR: n˜ =3326 (NH
2 2 2 3 3 3
stretch), 1682 (C=O), 1457 (CH ), 1392 (ꢀSO ꢀ), 1246 (CꢀO), 1165
3
2
ꢀ1
+
(
CꢀO), 1136 cm
(CꢀO); MS (ESI+): m/z: 490 [M+H] , 468
2-(2-Aminoethoxy)ethanol-N-(quinol-8-yl)acetamide (2)
+
[M+Na] .
Compound (0.24 g, 1.09 mmol), 2-(2-aminoethoxy)ethanol
1
(
1.14 g, 10.9 mmol), N,N-diisopropylethylamine (1.41 g, 10.9 mmol)
tert-Butyl 2,2’,2’’-{[2,2-(Boc)-aminoethoxyethyl-N-(quinol-8-
yl)acetamide]-1,4,7,10- tetraazacyclododecane-1,4,7-triyl} (5)
and a catalytic amount of potassium iodide (0.14 mmol) were
heated together under reflux conditions in acetonitrile (70 mL).
After 10 h, the mixture was cooled to room temperature and con-
centrated under reduced pressure to give a yellow oil. This was pu-
rified by means of silica gel column chromatography using 20%
MeOH in CHCl to give the title compound (0.30 g, 90%). H NMR
(
(
1
Compound 4 (71.7 mg, 0.153 mmol) was dissolved in dry acetoni-
trile (15 mL) and added dropwise to a solution of triester cyclen
(94.7 mg, 0.184 mmol) and triethylamine (0.11 mL, 0.767 mmol) in
dry acetonitrile (35 mL). After heating under reflux conditions for
72 h, the resulting reaction mixture was concentrated under re-
duced pressure to give a thick brown oil, which was purified by
means of column chromatography using silica gel (CH Cl /CH OH
1
3
3
CDCl ): d=8.83 (dd, J(H,H)=4.1, 1.6 Hz, 1H; NHCCHCHCH), 8.79
3
3
3
dd, J(H,H)=7.1, 1.6 Hz, 1H; NCHCHCH), 8.12 (dd, J(H,H)=8.3,
.4 Hz, 1H; NHCCHCHCH), 7.50 (m, 2H; NHCCHCHCH, NCHCHCH),
.24 (m, 1H; NCHCHCH), 3.72 (m, 4H; HNCH CH O), 3.57 (m, 4H;
2
2
3
7
95:5) to yield the title compound as a viscous light brown oil
2
2
3
13
1
OCH CH OH), 2.94 ppm (t, J(H,H)=4.9 Hz, 2H; CH NH); C NMR
(0.104 g, 77%). H NMR (CDCl ): d=10.29 (br, 1H; NCHCHCH), 10.06
2
2
2
3
(
(
(
(
CDCl ): d=170.8 (CO), 148.5 (NHCCHCHCH), 139.0 (NHCCN), 136.3
(br, 1H; HNꢀCO), 8.78 (m, 2H; NHCCHCHCH,), 8.21 (m, 1H;
NCHCHCH), 7.56–7.50 (m, 2H; NHCCHCHCH, NCHCHCH), 4.13 (2H;
CH CO), 3.65–3.60 (m, 4H; CH NCO), 3.45 (br, 2H; CH O), 4.36–3.46
3
NCHCHCH), 134.2 (NHCCCCH), 128.1 (NHCCHCHCH), 127.3
NCHCHCH), 121.8 (NHCCHCHCH), 121.5 (NCHCHCH), 116.7
NHCCHCHCH), 72.3 (COCH NH), 70.7 (OCH CH OH), 61.8
2
2
2
(16H; 6,8-CH , 5,9-CH 2,12-CH , 3,11-CH ), 1.42 (s, 9H; CH ),
2 2, 2 2 3
2
2
2
13
(
OCH CH OH), 53.8 (NHCH CH O), 49.4 ppm (NHCH CH O); IR: n˜ =
1.46 ppm (m, 27H; CH3); C NMR (CDCl ): d=172.6 (CO), 170.5
2
2
2
2
2
2
3
3
285 (OH and NH stretch), 1660 (C=O), 1596 (NH bend), 1324 (Cꢀ
(CO), 169.7 (CO), 168.1 (CO), 148.4 (NHCCHCHCH), 138.3 (NHCCN),
136.5 (NCHCHCH), 128.0 (NHCCHCHCH), 127.3 (NCHCHCH), 121.9
ꢀ1
+
+
N), 1118 (CꢀO), 1062 cm (CꢀO); MS (ESI ): m/z: 290 [M+H] .
Chem. Eur. J. 2015, 21, 5023 – 5033
5030 ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim