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Helvetica Chimica Acta – Vol. 90 (2007)
(S)-2-Phenyl-1,4,8-triazaoctane Trihydrochloride (¼ N1-[(2S)-2-Amino-2-phenylethyl]propane-1,3-
1
diamine Trihydrochloride; 9b): Yield 54%. H-NMR (CDCl3): 7.4 – 7.2 (m, Ph); 4.0 (t, J ¼ 7, CH); 3.9
(br. s, 2 NH2, NH); 3.7 (t, J ¼ 7, CH2); 3.2 (t, J ¼ 7, CH2); 3.1 (dd, J ¼ 13, 4, CH2); 1.8 – 1.7 (m, CH2).
Di(tert-Butyl) (S)-3,6,10-Tris[2-(tert-butoxy)-2-oxoethyl]-4-phenyl-3,6,10-triazadodecanedioate
(¼ N-{(2S)-2-{Bis[2-(tert-butoxy)-2-oxoethyl]amino}-2-phenylethyl}-N-{3-{bis[2-(tert-butoxy)-2-oxoe-
thyl]amino}propyl}glycine tert-Butyl Ester; 10b): Yield 25%. 1H-NMR (CDCl3): 7.25 – 7.15 (m, 3 H, Ph);
7.1 – 7.0 ( m, 2 H, Ph); 5.1 (t, J ¼ 6, CH); 3.9 (s, 2 CH2); 3.8 (s, 1 CH2); 3.7 (s, 2 CH2); 3.0 (dd, J ¼ 13, 4,
1 CH2); 2.5 (t, J ¼ 7, 1 CH2); 2.4 (t, J ¼ 7, 1 CH2); 2.2 – 2.1 (m, 1 CH2).
Ligand 11b (H5(4-Ph-ttda)): Yield 67%. 1H-NMR (D2O): 7.5 – 7.3 (m, Ph); 5.1 (t, J ¼ 6, CH); 4.1 (s,
1 CH2); 4 (d, J ¼ 7, 2 CH2); 3.9 (s, 2 CH2); 3.5 – 3.3 (m, 2 CH2); 3.1 (t, J ¼ 7, 1 CH2); 2.1 – 2.0 (m, CH2).
13C-NMR (D2O): 175.4; 172.9; 172.4; 169.1; 168.3; 139.4; 134.4; 133.3; 131.6; 60.1; 58.0; 55.8; 53.1; 52.1;
51.7; 50.2; 49.2; 48.3; 30.6. EI-MS: 508 (30, [M þ Na]þ), 486 (100, [M þ H]þ).
5.3. (RS)-3,6,10-Tris(carboxymethyl)-9-methyl-3,6,10-triazadodecanedioic Acid (¼ N-{(3RS)-3-
[Bis(carboxymethyl)amino]butyl}-N-{2-[bis(carboxymethyl)amino]ethyl}glycine; 17a; H5(9-Me-ttda)).
As described for 11a (Sect. 5.1), from (3RS)-3-aminobutanoic acid, but with ethane-1,2-diamine instead
of propane-1,3-diamine in the second step.
(3RS)-3-Aminobutanoic Acid Methyl Ester Hydrochloride (13a): Yield 98%. 1H-NMR (D2O): 3.8 (s,
MeO); 3.1 – 2.7 (m, 1 CH2); 2.5 – 2.4 (m, CH); 1.5 (d, J ¼ 7, Me(4)).
(3RS)-3-Amino-N-(2-aminoethyl)butanamide (14a): Yield 92%. 1H-NMR (D2O): 3.2 – 3.1 (m, CH);
3.1 – 2.9 (m, 1 CH2); 2.5 (t, J ¼ 7, 1 CH2); 2.1 (t, J ¼ 7, 1 CH2); 0.8 (dd, J ¼ 10, 4, Me(4)).
(RS)-7-Methyl-1,4,8-triazaoctane Trihydrochloride ¼ (3RS)-N1-(2-Aminoethyl)butane-1,3-diamine
Trihydrochloride; 15a): Yield 58%. 1H-NMR (D2O): 3.7 – 3.0 (m, 3 CH2, CH); 1.9 – 1.7 (m, 1 CH2); 1.2
(d, J ¼ 7, Me ) .
Di(tert-butyl (RS)-3,6,10-Tris[2-(tert-butoxy)-2-oxoethyl]-9-methyl-3,6,10-triazadodecanedioate
(¼ N-{(3RS)-3-{Bis[2-(tert-butoxy)-2-oxoethyl]amino}butyl}-N-{2-{bis[2-(tert-butoxy)-2-oxoethyl]ami-
1
no}ethyl}glycine tert-Butyl Ester; 16a): Yield 30%. H-NMR (CDCl3): 3.6 (s, 1 CH2); 3.5 – 3.1 (m, CH,
t
5 CH2); 2.9 – 2.7 (m, 2 CH2); 1.7 – 1.4 (m, CH2, 5 Bu); 1.0 (dd, J ¼ 10, 4, Me).
Ligand 17a (H5(9-Me-ttda)): Yield 55%. 1H-NMR (D2O): 3.7 (s, 1 CH2); 3.2 – 2.5 (m, CH, 5 CH2);
2.5 (t, J ¼ 7, 1 CH2); 2.4 (t, J ¼ 7, 1 CH2); 1.8 – 1.7 (m, 1 CH2); 1 (dd, J ¼ 10, 7, Me). 13C-NMR (D2O): 176.7;
173.0; 171.2; 169.1; 168.4; 63.9; 63.7; 60.0; 56.3; 55.7; 54.7; 53.4; 53.2; 49.3; 32.2; 13.5. EI-MS: 466 (26,
[M þ 2 Na]þ), 444 (42, [M þ Na]þ), 422 (100, [M þ H]þ).
5.4. (RS)-3,6,10-Tris(carboxymethyl)-9-phenyl-3,6,10-triazadodecanedioic Acid (¼ N-{2-[Bis(car-
boxymethyl)amino]ethyl}-N-{(3RS)-3-[bis(carboxymethyl)amino]-3-phenylpropyl}glycine (17b; H5(9-
Ph-ttda)). As described for 11a (Sect. 5.1), from (3RS)-3-amino-3-phenylpropano acid but with
ethane-1,2-diamine instead of propane-1,3-diamine in the second step.
1
(3RS)-3-Amino-3-phenylpropanoic Acid Methyl Ester Hydrochloride (13b): Yield 98%. H-NMR
(CDCl3): 8.7 (br. s, NH2); 7.5 – 7.4 (m, 2 H, Ph); 7.3 – 7.1 (m, 3 H, Ph); 4.6 (t, J ¼ 7, CH); 3.8 (s, MeO, 3 H);
3.3 (dd, J ¼ 10, 4, 1 CH2).
(3RS)-3-Amino-N-(2-aminoethyl)-3-phenylpropanamide (14b): Yield 98%. 1H-NMR (CDCl3): 7.4 –
7.2 ( m, Ph); 4.3 (t, J ¼ 7, CH); 3.2 – 3.1 (m, 1 CH2); 2.9 – 2.8 (m, 2 CH2); 1.7 (br. s, 2 NH2, NH).
7-Phenyl-1,4,8-triazaoctane Trihydrochloride (¼(1RS)-N3-(2-Aminoethyl)-1-phenylpropane-1,3-di
amine; 15b): Yield 58%. 1H-NMR (CDCl3): 7.5 – 7.4 (m, 2 H, Ph); 7.3 – 7.2 (m, 3 H, Ph); 5 (br. s,
2 NH2, NH); 4.3 (t, J ¼ 7, CH); 3.1 – 2.8 (m, 2 CH2); 1.65 – 1.55 (m, 1 CH2); 1.5 – 1.4 (m, 1 CH2).
Di(tert-Butyl) (RS)-3,6,10-Tris[2-(tert-butoxy)-2-oxoethyl]-9-phenyl-3,6,10-triazadodecanedioate
(¼ N-{2-{Bis[2-(tert-butoxy)-2-oxoethyl]amino}ethyl}-N-{(3RS)-3-{bis[2-(tert-butoxy)-2-oxoethyl]ami-
no}-3-phenylpropyl}glycine tert-Butyl Ester: Yield 27%. 1H-NMR (CDCl3): 7.3 (s, Ph); 3.7 (t, J ¼ 6, CH);
t
3.5 (s, 2 CH2); 3.45 (s, 2 CH2); 3 (s, CH2); 2.8 – 2.5 (m, 4 CH2); 1.4 (s, 5 Bu).
Ligand 17b (H5(9-Ph-ttda)): Yield 92%. 1H-NMR (D2O): 7.5 – 7.4 (m, Ph); 4.4 (t, J ¼ 6, CH); 3.8 – 3.5
(m, 5 CH2); 3.3 – 3.0 (m, 3 CH2); 2.5 – 2.4 (m, 1 CH2). 13C-NMR (D2O): 176.5; 170.7; 169.7; 168.2; 167.9;
137.2; 130.8; 130.0; 128.4; 61.4; 60.7; 59.6; 55.2; 55.1; 53.9; 51.6; 50.8; 49.8; 31.4. EI-MS: 530 (30, [M þ 2
Na]þ), 486 (100, [M þ H]þ).
6. Synthesis of the Corresponding Gd-Complexes. The Gd3þ complexes were prepared by mixing aq.
solns. of equimolar amounts of hexahydrated GdCl3 and one of the ligands 11a,b or 17a,b. The pH was