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5.2.11.
(2S,3S)-3-Methyl-2-[3-(6-methyl-pyridin-2-yl-
J = 8.8 Hz, 2H), 7.67 (d, J = 7.8 Hz, 1H), 7.37 (m,
1H), 7.19 (m, 7H), 6.53 (d, J = 8.5 Hz, 1H), 4.48 (d,
J = 15.3 Hz, 1H), 4.23 (d, J = 15.3 Hz, 1H), 4.18 (m,
1H), 3.83 (m, 2H), 3.74 (d, J = 10.9 Hz, 1H), 3.12 (m,
4H), 3.04 (m, 1H), 2.95 (m, 1H), 2.88 (m, 1H), 2.75
(dd, J = 14.2, 10.1 Hz, 1H), 1.98 (m, 1H), 1.86 (m,
1H), 1.35 (m, 1H), 0.97 (m, 1H), 0.92 (d, J = 6.8 Hz,
3H), 0.87 (d, J = 6.4 Hz, 3H), 0.83 (m, J = 7.5 Hz,
3H), 0.72 (d, J = 6.8 Hz, 3H); MS (ESI) m/z 691.5
[MꢀH]ꢀ, 693.3 [M+H]+, 715.3 [M+Na]+.
methyl)-2-oxo-imidazolidin-1-yl]-pentanoic acid ((1S,2R)-1-
benzyl-2-hydroxy-3-{[4-(E-hydroxyimino-methyl)-ben-
zenesulfonyl]-isobutyl-amino}-propyl)-amide (15). Using
the general method for peptide coupling described above
for the conversion of 10 to 11, compound 14 (50 mg,
0.14 mmol) was converted to the title compound 15,
obtained as a colorless, amorphous solid (56 mg, 57%):
1H NMR (300 MHz, CDCl3) d 8.51 (br s, 1H), 8.16 (s,
1H), 7.79 (d, J = 8.5Hz, 2H), 7.70 (d, J = 8.5 Hz, 2H),
7.58 (m, 1H), 7.18 (m, 5H), 7.06 (m, 2H), 6.49 (d,
J = 8.8 Hz, 1H), 4.59 (d, J = 15.6 Hz, 1H), 4.38 (d,
J = 15.6 Hz, 1H), 4.12 (m, 1H), 3.88 (d, J = 3.4 Hz,
1H), 3.80 (m, 2H), 3.13 (m, 6H), 2.94 (m, 1H), 2.83
(m, 1H), 2.74 (dd, J = 14.2, 10.2 Hz, 1H), 2.56 (s, 3H),
1.96 (m, 1H), 1.86 (m, 1H), 1.35 (m, 1H), 1.03 (m,
1H), 0.91 (d, J = 6.4 Hz, 3H), 0.85 (m, 6H), 0.73 (d,
J = 6.4 Hz, 3H); MS (ESI) m/z 705.4 [MꢀH]ꢀ, 707.3
[M+H]+, 729.3 [M+Na]+.
5.2.15. (2S,3S)-3-Methyl-2-[3-(6-methoxymethyl-pyridin-
2-ylmethyl)-2-oxo-imidazolidin-1-yl]-pentanoic
acid
((1S,2R)-1-benzyl-2-hydroxy-3-{[4-(E-hydroxyimino-meth-
yl)-benzenesulfonyl]-isobutyl-amino}-propyl)-amide (23).
The title compound was prepared using the method de-
scribed for the synthesis of 15, substituting 6-methoxym-
ethyl-2-pyridinecarboxaldehyde
for
6-methyl-2-
pyridinecarboxaldehyde (60% overall yield from 13):
1H NMR (300 MHz, CDCl3) d 8.17 (s, 1H), 8.15 (br s,
1H), 7.79 (d, J = 8.8 Hz, 2H), 7.68 (m, 3H), 7.32 (d,
J = 7.8 Hz, 1H), 7.17 (m, 5H), 6.50 (d, J = 8.5 Hz,
1H), 4.60 (d, J = 15.9 Hz, 1H), 4.56 (s, 2H), 4.37 (d,
J = 15.6 Hz, 1H), 4.17 (m, 1H), 3.81 (m, 3H), 3.48 (s,
3H), 3.14 (m, 6H), 2.99 (m, 1H), 2.84 (m, 2H), 2.75
(dd, J = 14.4, 10.0 Hz, 1H), 1.98 (m, 1H), 1.88 (m,
1H), 1.39 (m, 1H), 1.01 (m, 1H), 0.91 (d, J = 6.8 Hz,
3H), 0.85 (m, 6H), 0.74 (d, J = 6.8 Hz, 3H); MS (ESI)
m/z 735.4 [MꢀH]ꢀ, 737.3 [M+H]+, 759.3 [M+Na]+.
5.2.12. (2S,3S)-3-Methyl-2-[2-oxo-3-pyridin-4-ylmethyl-
imidazolidin-1-yl]-pentanoic acid ((1S,2R)-1-benzyl-2-hy-
droxy-3-{[4-(E-hydroxyimino-methyl)-benzenesulfonyl]-
isobutyl-amino}-propyl)-amide (20). The title compound
was prepared using the method described for the synthe-
sis of 15, substituting 4-pyridinecarboxaldehyde for
6-methyl-2-pyridinecarboxaldehyde (12% overall yield
from 13): 1H NMR (300 MHz, CDCl3) d 8.60 (br s,
2H), 8.16 (s, 1H), 7.80 (d, J = 8.1 Hz, 2H), 7.69 (d,
J = 8.5 Hz, 2H), 7.30 (m, 2H), 7.20 (m, 5H), 6.53 (d,
J = 8.8 Hz, 1H), 4.49 (d, J = 15.9 Hz, 1H), 4.27 (d,
J = 15.9 Hz, 1H), 4.23 (m, 1H), 3.79 (m, 2H), 2.96 (m,
9H), 2.00 (m, 1H), 1.87 (m, 2H), 1.37 (m, 1H), 1.01 (m,
1H), 0.87 (m, 9H), 0.76 (d, J = 6.4 Hz, 3H); MS (ESI)
m/z 691.4 [MꢀH]ꢀ, 693.3 [M+H]+, 715.3 [M+Na]+.
5.2.16. (2S,3S)-3-Methyl-2-[3-(6-isopropyl-pyridin-2-yl-
methyl)-2-oxo-imidazolidin-1-yl]-pentanoic acid ((1S,2R)-1-
benzyl-2-hydroxy-3-{[4-(E-hydroxyimino-methyl)-benze-
nesulfonyl]-isobutyl-amino}-propyl)-amide (24). The title
compound was prepared using the method described
for the synthesis of 15, substituting 6-isopropyl-2-pyri-
dinecarboxaldehyde for 6-methyl-2-pyridinecarboxalde-
5.2.13. (2S,3S)-3-Methyl-2-[2-oxo-3-pyridin-2-ylmethyl-
imidazolidin-1-yl]-pentanoic acid ((1S,2R)-1-benzyl-2-hy-
droxy-3-{[4-(E-hydroxyimino-methyl)-benzenesulfonyl]-
isobutyl-amino}-propyl)-amide (21). The title compound
was prepared using the method described for the synthe-
sis of 15, substituting 2-pyridinecarboxaldehyde for
6-methyl-2-pyridinecarboxaldehyde (43% overall yield
from 13): 1H NMR (300 MHz, CDCl3) d 8.56 (d,
J = 4.1 Hz, 1H), 8.16 (s, 2H), 7.79 (d, J = 8.5 Hz, 2H),
7.70 (d, J = 8.5 Hz, 3H), 7.68 (m, 1H), 7.22 (m, 7H),
6.53 (d, J = 8.8 Hz, 1H), 4.59 (d, J = 15.6 Hz, 1H), 4.40
(d, J = 15.6 Hz, 1H), 4.16 (m, 1H), 3.90 (m, 1H), 3.79
(m, 1H), 3.77 (d, J = 10.9 Hz, 1H), 3.14 (m, 5H), 2.99
(m, 1H), 2.87 (m, 2H), 2.75 (dd, J = 14.2, 10.2 Hz, 1H),
1.97 (m, 1H), 1.87 (m, 1H), 1.39 (m, 1H), 1.01 (m, 1H),
0.89 (m, 9H), 0.73 (d, J = 6.4 Hz, 3H); MS (ESI) m/z
691.3 [MꢀH]ꢀ, 693.3 [M+H]+, 715.2 [M+Na]+.
1
hyde (18% overall yield from 13): H NMR (300 MHz,
CDCl3) d 8.15 (s, 1H), 7.78 (d, J = 8.5 Hz, 2H), 7.69
(m, 2H), 7.19 (m, 5H), 7.08 (m, 2H), 6.50 (d,
J = 8.8 Hz, 1H), 4.58 (m, 1H), 4.39 (m, 1H), 4.12 (m,
1H), 3.86 (m, 1H), 3.75 (m, 2H), 3.02 (m, 11H), 2.75
(m, 1H), 1.87 (m, 2H), 1.29 (m, 6H), 1.01 (m, 1H),
0.88 (m, 9H), 0.73 (d, J = 6.4 Hz, 3H); MS (ESI) m/z
733.5 [MꢀH]ꢀ, 735.3 [M+H]+, 757.5 [M+Na]+.
5.2.17.
(2S,3S)-3-Methyl-2-[3-(2-methyl-pyridin-3-yl-
methyl)-2-oxo-imidazolidin-1-yl]-pentanoic acid ((1S,2R)-
1-benzyl-2-hydroxy-3-{[4-(E-hydroxyimino-methyl)-
benzenesulfonyl]-isobutyl-amino}-propyl)-amide (25). The
title compound was prepared using the method de-
scribed for the synthesis of 15, substituting 2-methyl-3-
pyridinecarboxaldehyde for 6-methyl-2-pyridinecarbox-
aldehyde (39% overall yield from 13): 1H NMR
(300 MHz, CDCl3) d 8.43 (dd, J = 5.0, 1.7 Hz, 1H),
8.16 (s, 1H), 7.79 (d, J = 8.5 Hz, 2H), 7.71
(d, J = 8.5 Hz, 2H), 7.45 (dd, J = 7.7, 1.5 Hz, 1H),
7.17 (m, 6H), 6.49 (d, J = 8.8 Hz, 1H), 4.42 (d,
J = 15.1 Hz, 1H), 4.26 (d, J = 15.4 Hz, 1H), 4.20 (m,
1H), 3.79 (m, 2H), 3.02 (m, 9H), 2.78 (dd, J = 14.3,
9.9 Hz, 1H), 2.55 (s, 3H), 1.99 (m, 1H), 1.85 (m,
1H), 1.33 (m, 1H), 1.00 (m, 1H), 0.90 (d,
J = 6.6 Hz, 3H), 0.85 (m, 6H), 0.75 (d, J = 6.6 Hz,
5.2.14. (2S,3S)-3-Methyl-2-[2-oxo-3-pyridin-3-ylmethyl-
imidazolidin-1-yl]-pentanoic acid ((1S,2R)-1-benzyl-2-hy-
droxy-3-{[4-(E-hydroxyimino-methyl)-benzenesulfonyl]-
isobutyl-amino}-propyl)-amide (22). The title compound
was prepared using the method described for the synthe-
sis of 15, substituting 3-pyridinecarboxaldehyde for
6-methyl-2-pyridinecarboxaldehyde (40% overall yield
from 13): 1H NMR (300 MHz, CDCl3) d 8.56 (br s,
2H), 8.16 (s, 1H), 7.79 (d, J = 8.5 Hz, 2H), 7.71 (d,