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N-CH3), 3.9±4.5 (m, 1H, CHN), 5.0 (s, 2H, CH2Ph), 6.0
(s, 1H, 5-H (pyridinone)), 7.2(s, 5H, Ar), 8.0±8.4 (br,
1H, NH); MS(FAB): m/z 314 [M+].
1,6-Dimethyl-3-hydroxypyridin-4(1H)-one-2-carboxy-
amide hydrochloride (15a). Yield 92%, mp 250 ꢀC (dec.).
1H NMR (DMSO-d6) d 2.4 (s, 3H, 6-CH3), 3.65 (s, 3H,
N-CH3), 4.7±5.7 (br., OH), 7.1 (s, 1H, 5-H (pyr-
idinone)), 8.0±8.5 (br, 2H, NH2); MS (FAB): m/z 183
[(M-Cl)+]. Anal. calcd for C8H11ClN2O3: C, 43.95; H,
5.07; N, 12.81; Cl, 16.22%. Found: C, 44.23; H, 5.21; N,
12.97; Cl, 16.43%.
1,6-Dimethyl-3-benzyloxy-pyridin-4(1H)-one-2-carboxy-
(N-20-methoxyethyl)-amide (14d). Puri®cation by col-
umn chromatography on silica gel (eluant: methanol:
chloroform; 10:90 v/v) followed by recrystallisation
from methanol/diethyl ether aorded a white crystalline
ꢀ
1
solid (yield 82%), mp 125±126 C. H NMR (CDCl3) d
2.1 (s, 3H, 6-CH3), 3.2(s, 3H, OCH3), 3.1±3.7 (m, 4H,
CH2CH2), 3.4 (s, 3H, N±CH3), 4.95 (s, 2H, CH2Ph), 6.0
(s, 1H, 5-H (pyridinone)), 7.0±7.5 (m, 5H, Ar), 7.8±8.4
(br, 1H, NH); MS (FAB): m/z 330 [M+].
1,6-Dimethyl-3-hydroxypyridin-4(1H)-one-2-carboxy-(N-
methyl)-amide hydrochloride (15b). Yield 93%, mp 239±
240 ꢀC. H NMR (DMSO-d6) d 2.5 (s, 3H, 6-CH3), 2.75
1
(d, 3H, CH3NH, J=6.0 Hz), 3.7 (s, 3H, N±CH3), 7.2(s,
1H, 5-H (pyridinone)), 6.8±8.1 (br, OH), 8.7±9.2(br, 1H,
NH); MS (FAB): m/z 197 [(M-Cl)+]. Anal. calcd for
C9H13ClN2O3: C, 46.46; H, 5.63; N, 12.04; Cl, 15.24%.
Found: C, 46.31; H, 5.76; N, 11.85; Cl, 15.13%.
1,6-Dimethyl-3-benzyloxy-pyridin-4(1H)-one-2-carboxy-
(N-20-hydroxyethyl)-amide (14e). Puri®cation by col-
umn chromatography on silica gel (eluant: methanol:
chloroform; 15:85 v/v) followed by recrystallisation
from methanol/diethyl ether aorded a white crystalline
1,6-Dimethyl-3-hydroxypyridin-4(1H)-one-2-carboxy-(N-
isopropyl)-amide hydrochloride (15c). Yield 93%, mp
solid (yield, 86%), mp 153±155 ꢀC. H NMR (CDCl3)
219±220 ꢀC. H NMR (DMSO-d6) d 1.15 (d, 6H, CH
1
1
d 2.1 (s, 3H, 6-CH3), 3.1±3.7 (m, 4H, CH2CH2), 3.4 (s,
3H, N±CH3), 4.95 (s, 2H, CH2Ph), 6.02(s, 1H, 5-H
(pyridinone)), 7.0±7.5 (m, 5H, Ar), 7.8±8.4 (br, 1H,
NH); MS (FAB): m/z 316 [M+].
(CH3)2, J=6.0 Hz), 2.5 (s, 3H, 6-CH3), 3.7 (s, 3H, N-
CH3), 3.6±4.4 (m, 1H, CHNH), 5.2±6.5 (br, OH), 7.3 (s,
1H, 5-H(pyridinone)), 8.8±9.2(br, 1H, NH); MS (FAB):
m/z 225 [(MÀCl)+]. Anal. calcd for C11H17ClN2O3: C,
50.67; H, 6.57; N, 10.74; Cl, 13.60%. Found: C, 50.38;
H, 6.81; N, 10.56; Cl, 13.87%.
1,6-Dimethyl-3-benzyloxy-pyridin-4(1H)-one-2-carboxy-
(N-benzyl)-amide (14f). Puri®cation by column chroma-
tography on silica gel (eluant: methanol:chloroform;
12:88 v/v) followed by recrystallisation from methanol/
diethyl ether aorded a white crystalline solid (yield,
1,6-Dimethyl-3-hydroxypyridin-4(1H)-one-2-carboxy-(N-
20-methoxyethyl)-amide hydrochloride (15d). Yield 90%,
mp 204±206 ꢀC. H NMR (DMSO-d6) d 2.6 (s, 3H, 6-
1
80%), mp 203±206 ꢀC. H NMR (CDCl3) d 1.9 (s, 3H,
CH3), 3.4 (s, 3H, OCH3), 3.1±3.6 (m, 4H, CH2CH2), 3.8
(s, 3H, N±CH3), 7.35 (s, 1H, 5-H (pyridinone)), 8.8±10.05
(br, OH and NH); MS (FAB): m/z 241 [(M-Cl)+]. Anal.
calcd for C11H17ClN2O4: C, 47.74; H, 6.19; N, 10.12 ; Cl,
12 .81%. Found: C, 47.56; H, 6.30; N, 10.36; Cl, 13.04%.
1
6-CH3), 3.4 (s, 3H, N±CH3), 4.4 (d, 2H, NHCH2Ph,
J=6.0 Hz), 4.8 (s, 2H, CH2Ph), 5.6 (s, 1H, 5-H (pyr-
idinone)), 7.0±7.5 (m, 10H, Ar), 8.7±9.2(br., 1H, NH);
MS (FAB): m/z 362[M +].
1,6-Dimethyl-3-benzyloxy-pyridin-4(1H)-one-2-carboxy-
(N-phenyl)-amide (14g). Recrystallisation from metha-
nol/diethyl ether aorded a white crystalline solid (yield
1,6-Dimethyl-3-hydroxypyridin-4(1H)-one-2-carboxy-(N-
20-hydroxyethyl)-amide hydrochloride (15e). Yield 91%,
mp 178±181 ꢀC. H NMR (DMSO-d6) d 2.55 (s, 3H,
1
92%), mp 132±135 ꢀC. H NMR (DMSO-d6) d 2.2 (s,
6-CH3), 3.1±3.7 (m, 4H, CH2CH2), 3.85 (s, 3H, N±CH3),
7.25 (s, 1H, 5-H (pyridinone)), 6.7±8.2(br., OH), 9.1 (br.,
1H, NH); MS (FAB): m/z 227 [(M-Cl)+]. Anal. calcd for
C10H15ClN2O4: C, 45.72; H, 5.76; N, 10.66; Cl, 13.50%.
Found: C, 45.47; H, 5.98; N, 10.48; Cl, 13.27%.
1
3H, 6-CH3), 3.4 (s, 3H, N-CH3), 4.95 (s, 2H, CH2Ph),
6.1 (s, 1H, 5-H(pyridinone)), 6.8±7.7 (m, 10H, Ar); MS
(FAB): m/z 348 [M+].
1,6-Dimethyl-3-benzyloxy-pyridin-4(1H)-one-2-carboxy-
(N-30-pyridyl)-amide (14h). Recrystallisation from meth-
anol/diethyl ether aꢀorded a yellow crystalline solid
(yield 78%), mp 200 C dec. 1H NMR (DMSO-d6) d 2.2
(s, 3H, 6-CH3), 3.4 (s, 3H, N±CH3), 5.0 (s, 2H, CH2Ph),
6.1 (s, 1H, 5-H (pyridinone)), 6.9±7.4 (m, 6H, Ar & 5-H
(pyridine)), 7.8±8.7 (m, 3H, 2,4,6-H (pyridine)); MS
(FAB): m/z 349 [M+].
1,6-Dimethyl-3-hydroxypyridin-4(1H)-one-2-carboxy-(N-
benzyl)-amide hydrochloride (15f). Yield 87%, mp 180±
ꢀ
1
183 C. H NMR (DMSO-d6) d 2.5 (s, 3H, 6-CH3), 3.7
(s, 3H, N±CH3), 4.4 (m, 2H, NHCH2Ph), 7.0±7.5 (m,
6H, Ar and 5-H (pyridinone)), 7.7±8.9 (br., OH), 9.3±9.8
(br., 1H, NH); MS (FAB): m/z 273 [(MÀCl)+]. Anal.
calcd for C15H17ClN2O3: C, 58.35; H, 5.55; N, 9.07; Cl,
11.48% Found: C, 58.57; H, 5.68; N, 8.98; Cl, 11.36%.
General procedure for the preparation of 15a±h. Solu-
tions of 14a±h in N,N-dimethylformamide (DMF) were
subjected to hydrogenolysis in presence of 5% Pd/C (5±
10% w/w of the compound) catalyst for 3 h. The cata-
lysts were removed by ®ltration and the ®ltrates were
acidi®ed to pH 1 with concentrated hydrochloric acid.
After removal of the solvents in vacuo, the residues were
puri®ed by recrystallization from methanol/diethyl
ether.
1,6-Dimethyl-3-hydroxypyridin-4(1H)-one-2-carboxy-(N-
phenyl)-amide hydrochloride (15g). Yield 92%, mp 261±
263 ꢀC. H NMR (methanol-d4) d 2.35 (s, 3H, 6-CH3),
1
3.65 (s, 3H, N±CH3), 6.8±7.6 (m, 6H, Ar and 5-H(pyr-
idinone)); MS (FAB): m/z 348 [M+.]. MS (FAB): m/z
259 [(MÀCl)+]. Anal. calcd for C14H15ClN2O3: C,
57.05; H, 5.13; N, 9.50; Cl, 12.03%. Found: C, 57.38; H,
5.26; N, 9.69; Cl, 11.96%.