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N-Iodoacetyl-n-hexylamine (14d)
DOTAM-methyl (10)
1
Pale yellow solid; 925 mg, 92%. H NMR (CDCl3) ␦: 6.21 (s, D2O
exch., 1H), 3.70 (s, 2H), 3.26 (m, 2H), 1.52 (m, 2H), 1.30 (m, 6H),
0.89 (m, 3H). 13C NMR (CDCl3) ␦: 166.6, 40.5, 31.4, 29.2, 26.4, 22.5,
14.0, −0.2. HR-MS (EI) m/z calcd. for C8H16INO: 269.0277; found:
269.0272 [M]+. LR-MS (EI) m/z (rel. abundance): 269 [M+] (22), 226
(12), 198 (36), 169 (20), 142 (100), 84 (40), 72 (74).
Colourless crystals; 143 mg, 85%; mp 211–214 °C (decomposition).
1H NMR (DMSO-d6) ␦: 7.99 (m, D2O exch., 4H), 2.85 (br s, 16H), 2.61
(m, 12H). 13C NMR (DMSO-d6) ␦: 168.9, 56.2, 50.5, 25.3. HR-MS (EI)
m/z calcd. for C20H41N8O4: 457.3251; found: 457.3245 [M + H]+.
Metallation of ligands 5–10 with DyCl3·6H2O, TbCl3·6H2O,
and TmCl3·6H2O
N-Iodoacetyl-n-octylamine (14e)
Separate solutions of ligands (5 and 6, 79 mg; 7, 80 mg; 8, 85 mg;
9, 90 mg; 10, 46 mg; 0.11 mmol each) in dioxane (5–9, 2 mL) or
water (10, 2 mL) were treated with the solutions of lanthanide(III)
chlorides hexahydrates (Dy3+, 46 mg; Tb3+, 45 mg; Tm3+, 49 mg) in
water (500 L). The mixtures were stirred for 24 h at 70 °C (ligands
5–9) or rt (ligand 10). The mixtures were concentrated and puri-
fied by FCC on 15 g Al2O3, CH2Cl2/MeOH/NH4OH 60:39:1 (com-
plexes derived from ligands 5–9) or by SEC (complexes derived
from ligand 10) as described in the General experimental proce-
dures. The fractions containing the complexes derived from li-
gands 5–9 were concentrated, dissolved in small amount of water
(3 mL), the pH was adjusted to ϳ7 (1 mol/L HCl), and the solutions
were dialyzed for 120 h. The fractions containing the complexes
derived from ligand 10 were concentrated, dissolved in small
amount of water (3 mL), and the solutions were dialyzed for 120 h.
The dialyzed solutions were lyophilized to leave the complexes as
colourless solids.
Pale yellow crystals; 1.923 g, 95%; mp 50–53 °C. 1H NMR (CDCl3)
␦: 6.63 (s, D2O exch., 1H), 3.70 (s, 2H), 3.23 (m, 2H), 1.50 (m, 2H),
1.26 (m, 10H), 0.85 (m, 3H). 13C NMR (CDCl3) ␦: 167.2, 40.4, 31.7, 31.7,
29.1 (3 × C), 26.7, 22.5, 14.0, −0.2. HR-MS (EI) m/z calcd. for
C10H20INO: 297.0590; found: 297.0595 [M]+. LR-MS (EI) m/z (rel.
abundance): 297 [M+] (10), 170 (100), 128 (13), 72 (68).
N-Iodoacetyl-methylamine (14f)
Colourless crystals; 842 mg, 42%; mp 63–66 °C. 1H NMR (CDCl3)
␦: 6.99 (s, D2O exch., 1H), 3.72 (s, 2H), 2.81 (d, J = 4.7 Hz, 3H). 13C NMR
(CDCl3) ␦: 168.3, 27.2, −0.5. HR-MS (EI) m/z calcd. for C3H6INO:
198.9494; found: 198.9501 [M]+. LR-MS (EI) m/z (rel. abundance):
198 [M+] (82), 168 (17), 126 (100), 72 (67).
DOTAM-alkyl ligands 5–10
DIPEA (280 L, 1.6 mmol) was added to separate solutions of
cyclen (1; 69 mg, 0.4 mmol) in MeCN (4 mL). The mixtures were
stirred for 10 min at 45 °C, followed by the addition of N-iodoacetyl
amides (14a and 14b, 386 mg; 14c, 442 mg; 14d, 407 mg; 14e,
475 mg; 14f, 318 mg; 1.6 mmol each). The stirring continued for a
further 24 h at 45 °C, the mixtures were cooled to rt, diluted with
water (20 mL each), and extracted by EtOAc (3 × 20 mL each). The
combined organic extracts were dried and concentrated, and li-
gands 5–10 were purified by crystallization from MeCN.
Dy3+ DOTAM-sec-butyl (5a)
27 mg, 31%. 1H NMR (D2O) ␦: 255.31 (s), 62.03 (s), 53.35 (s), 48.57–
41.48 (m), 36.67–31.11 (m), 27.37–25.86 (m), 20.81 (s), 12.84–
10.43 (m), 3.59–0.91 (m), −1.10 to −1.77 (m), −7.77 to −16.25 (m),
−20.16 to −26.84 (m), −73.72 to −78.75 (m), −87.35 to −93.35 (m),
−115.96 (s), −157.74 to −163.20 (m). HR-MS (EI) m/z calcd. for
C32H62N8O4161Dy: 783.4163; found: 783.4147 [M – 2H]+.
Tb3+ DOTAM-sec-butyl (5b)
DOTAM-sec-butyl (5)
36 mg, 42%. 1H NMR (D2O) ␦: 204.91–197.62 (m), 118.28 (s), 65.19–
58.05 (m), 36.25–30.68 (m), 19.18–15.11 (m), 8.76 (s), 3.19 to −1.38 (m),
−5.55 to −10.40 (m), −54.75 (s), −83.25 (s), −86.43 (s), −132.51 (s),
−141.72 (s), −316.74 (s), −320.20 (s). HR-MS (EI) m/z calcd. for
C32H62N8O4159Tb: 781.4148; found: 781.4178 [M – 2H]+.
Colourless crystals; 120 mg, 43%; mp 157–160 °C (decomposition).
1H NMR (CDCl3) ␦: 6.94 (m, D2O exch., 4H), 3.83 (m, 4H), 3.10 (m,
8H), 2.10–2.80 (br m, 16H), 1.54 (m, 8H), 1.13 (m, 12H), 0.87 (m, 12H).
13C NMR (CDCl3) ␦: 170.4, 170.3, 170.2, 57.6, 52.8, 50.5, 47.2 (2 × C),
47.1, 29.5, 29.2, 20.3, 20.0, 19.9, 10.6. HR-MS (EI) m/z calcd. for
C32H65N8O4: 625.51.5129; found: 625.5118 [M + H]+.
Tm3+ DOTAM-sec-butyl (5c)
32 mg, 37%. 1H NMR (D2O) ␦: 241.76–238.21 (m), 130.99–126.78 (m),
85.89 (s), 42.37 (s), 36.93 (s), 22.20–18.84 (m), 8.40 (s), 1.92 to −1.01 (m),
−11.33 to −14.13 (m), −53.76 (s), −81.98 to −89.04 (m). HR-MS (EI) m/z
calcd. for C32H62N8O4169Tm: 791.4236; found: 791.4236 [M – 2H]+.
DOTAM-tert-butyl (6)
Colourless crystals; 142 mg, 53%; mp 199–202 °C (decomposition).
1H NMR (CD3OD) ␦: 3.05 (br s, 8H), 2.79 (br s, 16H), 1.36 (s, 36H). 13
C
NMR (CD3OD) ␦: 173.0, 60.6, 54.5, 52.1, 29.3. HR-MS (EI) m/z calcd.
for C32H65N8O4: 625.5129; found: 625.5114 [M + H]+.
Dy3+ DOTAM-tert-butyl (6a)
46 mg, 53%. 1H NMR (D2O) ␦: 267.13 (s), 145.56 (s), 92.89 (s), 77.40 (s),
16.67 (s), 1.40 (s), −1.68 (s), −66.41 (s), −90.53 (s), −96.22 (s), −268.22 (s).
HR-MS (EI) m/z calcd. for C32H62N8O4161Dy: 783.4163; found:
783.4127 [M – 2H]+.
DOTAM-benzyl (7)
Colourless crystals; 136 mg, 45%; mp 194–197 °C. 1H NMR (CDCl3)
␦: 7.73 (m, 20H), 7.12 (m, D2O exch., 4H), 4.29 (d, J = 5.9 Hz, 8H),
2.90 (br s, 8H), 2.45 (br s, 16H). 13C NMR (CDCl3) ␦: 170.4, 138.4,
128.8, 127.8, 127.6, 58.9, 53.8, 43.0. HR-MS (EI) m/z calcd. for
C44H57N8O4: 761.4503; found: 761.4517 [M + H]+.
Tb3+ DOTAM-tert-butyl (6b)
33 mg, 38%. 1H NMR (D2O) ␦: 215.94 (s), 120.81 (s), 66.86 (s),
49.33 (s), 15.34 (s), 3.66 (s), 1.29 (s), −64.92 (s), −87.79 (s), −89.77 (s),
−200.77 (s). HR-MS (EI) m/z calcd. for C32H62N8O4159Tb: 781.4148;
found: 781.4185 [M – 2H]+.
DOTAM-n-hexyl (8)
Colourless crystals; 214 mg, 73%; mp 134–137 °C. 1H NMR (CDCl3)
␦: 7.73 (m, D2O exch., 4H), 3.64 (br s, 8H), 3.22 (m, 8H), 3.07 (br s, 16H),
1.53 (m, 8H), 1.29 (m, 24H), 0.88 (m, 12H). 13C NMR (CDCl3) ␦: 168.7,
57.5, 51.8, 39.6, 31.4, 29.4, 26.7, 22.6, 14.0. HR-MS (EI) m/z calcd. for
C40H81N8O4: 737.6381; found: 737.6404 [M + H]+.
Tm3+ DOTAM-tert-butyl (6c)
54 mg, 63%. 1H NMR spectrum is described in ref. 31 HR-MS (EI) m/z
calcd. for C32H62N8O4169Tm: 791.4236; found: 791.4202 [M – 2H]+.
DOTAM-n-octyl (9)
Colourless crystals; 158 mg, 53%; mp 123–127 °C. 1H NMR (CDCl3)
␦: 7.22 (m, D2O exch., 4H), 3.62 (br s, 8H), 3.19 (br s, 8H), 3.05 (br s, 16H),
1.51 (m, 8H), 1.26 (m, 40H), 0.86 (m, 12H). 13C NMR (CDCl3) ␦: 168.7,
57.5, 51.8, 41.8, 39.5, 31.7, 29.4, 29.2 (2 × C), 27.0, 22.6, 14.0. HR-MS (EI)
m/z calcd. for C48H97N8O4: 849.7633; found: 849.7635 [M + H]+.
Dy3+ DOTAM-benzyl (7a)
60 mg, 59%. 1H NMR (D2O) ␦: 253.86 (s), 129.34 (s), 81.88 (s), 45.16 (s),
31.27 (s), 27.41 (s), 24.42 (s), 22.95 (s), 1.72 (s), −86.72 (s), −89.35 (s),
−379.92 (s). HR-MS (EI) m/z calcd. for C44H54N8O4161Dy: 919.3537;
found: 919.3510 [M – 2H]+.
Published by NRC Research Press