T. Maruyama et al. / Bioorg. Med. Chem. 15 (2007) 392–402
399
collected by filtration to give 157 mg of the title com-
pound 8.
m), 9.52 (1H, s), 9.78 (1H, s); FABHRMS calcd for
C23H25N6O7S2 [(M+H)+]: 561.1221, found: 561.1223;
HPLC analysis: 96.0% (Area %).
NMR (DMSO-d6) d: 1.20 (3H, d, J = 6.3 Hz), 1.25 (3H,
d, J = 7.2 Hz), 3.47 (1H, dd, J1 = 6.0 Hz, J2 = 3.3 Hz),
3.75–3.85 (1H, m), 4.0–4.1 (1H, m), 4.38 (1H, dd,
J1 = 10.2 Hz, J2 = 3.3 Hz), 5.42 (1H, d, J = 13.8 Hz),
5.5–5.6 (3H, m), 7.7–7.8 (3H, m), 8.08 (1H, br s), 8.22
(2H, d, J = 8.7 Hz), 8.3–8.4 (1H, m), 8.57 (1H, s), 8.69
(1H, s), 9.15–9.2 (1H, m), 9.55–9.6 (1H, m), 9.76 (1H,
s); FABHRMS calcd for C38H27N6O8S [(MÀI)+]:
631.1611, found: 631.1600.
5.21. (1S,5R,6S)-2-[7-(1-Benzylpyridinium-3-yl)carbony-
limidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-
methyl-1-carbapen-2-em-3-carboxylate (intramolecular
salt) (9d)
The title compound (9d) was obtained in 7.8% yield
from compound 6 and benzyl bromide by a procedure
similar to that employed for the preparation of 8–9b.
5.18. (1S,5R,6S)-2-[7-(1-Carbamoylmethylpyridinium-
3-yl)-carbonylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-
hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate
(intramolecular salt) (9b)
NMR (D2O) d: 1.0–1.15 (3H, m), 1.30 (3H, d,
J = 6.0 Hz), 3.35–3.5 (2H, m), 4.1–4.3 (2H, m), 5.86
(2H, s), 7.4–7.6 (5H, m), 7.85–8.1 (3H, m), 8.8–9.0
(2H, m), 9.6–9.7 (1H, m); FABHRMS calcd for
C28H25N4O5S [(M+H)+]: 529.1540, found: 529.1544;
HPLC analysis: 94.3% (Area %).
The title compound (9b) (1.62 g) was obtained from
4.43 g of compound 8 by a procedure similar to that em-
ployed for the preparation of 7g.
5.22. (1S,5R,6S)-2-[7-(1-Carboxymethyl-pyridinium-3-
yl)carbonylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxy-
ethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (intra-
molecular salt) (9e)
NMR (D2O) d: 1.16 (3H, d, J = 7.5 Hz), 1.33 (3H, d,
J = 6.0 Hz), 3.4–3.55 (2H, m), 4.15–4.35 (2H, m), 5.65
(2H, s), 7.89 (1H, s), 8.03 (1H, s), 8.1–8.2 (1H, m),
8.85–8.95 (1H, m), 9.15–9.2 (1H, m), 9.58 (1H, s); FAB-
HRMS calcd for C23H22N5O6S [(M+H)+]: 496.1285,
found: 496.1277; HPLC analysis: 97.6% (Area %).
The title compound (9e) was obtained in 16% yield from
compound 6 and 4-nitrobenzyloxycarbonylmethyl triflu-
oromethanesulfonate by a procedure similar to that em-
ployed for the preparation of 8–9b.
5.19. (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-[7-
(1-methylpyridinium-3-yl)carbonylimidazo[5,1-b]-thiazol-
2-yl]-1-carbapen-2-em-3-carboxylate (intramolecular salt)
(9a)
NMR (D2O) d: 1.18 (3H, d, J = 7.3 Hz), 1.35 (3H, d,
J = 6.3 Hz), 3.55 (1H, m), 3.64 (1H, m), 4.27–4.37 (2H,
m), 5.39 (2H, s), 8.15 (1H, s), 8.24 (1H, m), 8.29 (1H,
s), 8.97 (1H, m), 9.25 (1H, m), 9.67 (1H, s); FABHRMS
calcd for C23H21N4O7S [(M+H)+]: 497.1125, found:
497.1129; HPLC analysis: 97.3% (Area %).
The title compound (9a) was obtained in 19% yield from
compound 6 and methyl trifluoromethanesulfonate by a
procedure similar to that employed for the preparation
of 8–9b.
5.23. (1S,5R,6S)-2-[7-(1-Ethoxycarbonylmethyl-pyridin-
ium-3-yl)carbonylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-
hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate
(intramolecular salt) (9f)
NMR (D2O) d: 1.13 (3H, d, J = 7.1 Hz), 1.35 (3H, d,
J = 6.3 Hz), 3.48–3.56 (2H, m), 4.23 (1H, dd,
J1 = 9.3 Hz, J2 = 2.7 Hz), 4.29 (1H, m), 4.55 (3H, s),
8.02 (1H, s), 8.15 (1H, s), 8.18 (1H, s), 8.98 (1H, s),
9.17 (1H, s), 9.66 (1H, s); FABHRMS calcd for
C22H21N4O5S [(M+H)+]: 453.1227, found: 453.1232;
HPLC analysis: 95.4% (Area %).
The title compound (9f) was obtained in 13% yield from
compound 6 and ethoxycarbonylmethyl bromide by a
procedure similar to that employed for the preparation
of 8–9b.
5.20. (1S,5R,6S)-6-((1R)-1-Hydroxyethyl)-1-methyl-2-[7-
[1-(2- sulfamoylaminoethyl)pyridinium-3-yl]carbonylimi-
dazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate
(intramolecular salt) (9c)
NMR (DMSO-d6) d: 1.03–1.25 (9H, m), 3.02–3.10 (1H,
m), 3.33–3.48 (1H, m), 3.82–3.94 (1H, m), 3.95–4.05
(1H, m), 4.19 (2H, t, J = 7.6 Hz), 4.95 (1H, m), 5.71
(2H, s), 8.22 (1H, s), 8.30–8.36 (2H, m), 9.11 (1H, m),
9.59 (1H, m), 9.75 (1H, s); FABHRMS calcd for
C25H25N4O7S [(M+H)+]: 525.1438, found: 525.1439;
HPLC analysis: 97.6% (Area %).
The title compound (9c) was obtained in 28% yield from
compound 6 and 2-(4-nitrobenzyloxycarbonyl-amin-
osulfonyl)aminoethyl trifluoromethanesulfonate by a
procedure similar to that employed for the preparation
of 8–9b.
5.24. (1S,5R,6S)-2-[7-(1-Acetoxymethyl-pyridinium-3-
yl)carbonylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxy-
ethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (intra-
molecular salt) (9g)
NMR (DMSO-d6) d: 1.14–1.21 (6H, m), 3.16 (1H, dd,
J1 = 6.0 Hz, J2 = 2.6 Hz), 3.42–3.57 (3H, m), 3.95 (1H,
m), 4.09 (1H, dd, J1 = 9.5 Hz, J2 = 2.7 Hz), 4.84 (2H,
m), 5.07 (1H, d, J = 4.2 Hz), 6.80 (2H, s), 7.29 (1H, br
s), 8.27 (1H, s), 8.32 (1H, m), 8.35 (1H, s), 9.14 (1H,
The title compound (9g) was obtained in 30% yield from
compound 6 and dichloroacetone by a procedure similar
to that employed for the preparation of 8–9b.