356
Majid Y. Moridani et al
+
+
}
column chromatography was 90% EtOAc±MeOH; (M ). Measured. m z ¯ 289.1198 (M ); Anal. Calcd for
yield 90% as a white crystalline solid; m.p. 83±85°C; 1H C15H16N2O4 [ 2H2O: C, 55.5; H, 6.2; N, 8.6% . Found:
NMR (CDCl3): d ¯ 2.15 (s, 3H, CH3), 2.41 (t, 2H, C, 55.6; H, 5.7; N, 8.5% .
CH2CONH), 2.95 (t, 2H, CH2CH2CONH), 3.15 (s, 3H,
NCH3), 4.27 (d, 2H, HNCH2, J ¯ 5.6 Hz), 5.05 (s, 2H,
CH2Ph), 5.16 (s, 2H, CH2Ph), 5.62 (t, 1H, NH, J ¯
5.6 Hz), 6.25 (s, 1H, H5), 6.82±7.41 (m, 14H, aromatic)
1,6-Dimethyl-2-[(2-hydroxyphenyl)-acetamido]methyl-
3-hydroxy-4(1H)-pyridinone (14b) Yield 20% ; m.p.
182±183°C; IR (KCl): 3206, 1670, 1628, 1540, 1460,
+
}
ppm. MS (EI): m z¯ 497 (M ); Anal. Calcd for
1
1360, 760 cm 1 ; H NMR (DMSO-d6): d ¯ 2.5 (d, 3H,
CH3, J ¯ 1.6 Hz), 3.43 (s, 2H, CH2CONH), 3.84 (s, 3H,
NCH3), 4.61 (d, 2H, HNCH2, J ¯ 5 Hz), 6.70±7.07 (m,
4H, aromatic), 7.16 (s, 1H, H5), 8.72 (t, 1H, NH, J ¯
-
C31H32N2O4 [ H2O: C, 72.4; H, 6.7; N, 5.4% . Found: C,
72.6; H, 6.4; N, 5.6% .
5 Hz), 9.6 (s, broad, 1H, OH) ppm. MS (accurate mass,
1,6 - Dimethyl-2-[4-(2-benzyloxyphenyl)-n-butanamido]-
methyl-3-benzyloxy-4(1H)-pyridinone The eluant for
column chromatography was 90% EtOAc±MeOH.
Recrystallisation of the crude compound from EtOAc
gave 1,6-dimethyl-2-[4-(2-benzyloxyphenyl)-n-butan-
+
}
high resolution, FAB): Actual. m z¯ 303.1345 (M ).
+
}
Measured. m z¯ 303.1344 (M ); Anal. Calcd for
C16H18N2O4 [ 2H2O: C, 55.8; H, 6.5; N, 8.3% . Found:
C, 55.7; H, 6.0; N, 8.1% .
amido]methyl-3-benzyloxy-4(1H)-pyridinone
(yield
1
70% ) as a wax. H NMR (CDCl3): d ¯ 1.95 (m, 2H,
CH2CH2CONH), 1.95 (t, 2H, CH2-CO), 2.2 (s, 3H,
CH3), 2.65 (t, 2H, CH2), 3.4 (s, 3H, NCH3), 4.3 (d, 2H,
HNCH2, J ¯ 6 Hz), 5.05 (s, 2H, CH2Ph), 5.2 (s, 2H,
CH2Ph), 5.4 (t, 1H, HN, J¯ 6 Hz), 6.35 (s, 1H, H5),
1,6-Dimethyl-2-[3-(2-hydroxyphenyl)-propanamido]-
methyl-3-hydroxy-4(1H)-pyridinone (14c) Yield 50% ;
m.p. 248±250°C; IR (KCl): 3284, 1636, 1569, 1507,
1
1
-
1450, 1243, 770 cm ; H NMR (DMSO-d6): d ¯ 2.27
(s, 3H, CH3), 2.38 (t, 2H, CH2CH2CONH), 2.75 (t,
2H, CH2CH2CONH), 3.37 (s, 3H, NCH3), 4.42 (d, 2H,
HNCH2, J¯ 5 Hz), 6.12 (s, 1H, H5), 6.65±7.03 (m, 4H,
aromatic), 8.20 (t, 1H, NH, J ¯ 5 Hz) ppm. MS (ac-
}
6.8±7.4 (m, 14H, aromatic) ppm. MS (FAB): m z¯
1
+
511 (M ); Anal. Calcd for C32H34N2O4 [ 22H2O: C, 74.0;
H, 6.8; N, 5.4% . Found: C, 73.9; H, 6.6; N, 5.4% .
}
curate mass, high resolution, FAB): Actual. m z¯
+
+
}
317.1501 (M ). Measured. m z¯ 317.1509 (M ); Anal.
Calcd for C17H20N2O4 [ 13CH3OH: C, 63.7; H, 6.6; N,
8.6% . Found: C, 63.9; H, 6.5; N, 8.4% .
Phenolate-type 3-hydroxy-4(1H)-pyridinone (14)
(general method)
Nitrogen gas was passed over a solution of 30±40 mL of
methanol containing compound 19 (2.4 mmol) for a
period of 3±5 min. The reaction was then followed by
the addition of palladium 5% on activated carbon
1,6-Dimethyl-2-[4-(2-hydroxyphenyl)-n-butanamido]-
methyl-3-hydroxy-4(1H)-pyridinone (14d) Yield 70% ;
m.p 242±244°C. IR (KCl): 3194, 1647, 1580,
}
(5±10% w w of compound 19). Nitrogen gas was again
1
passed over the solution for a period of 3±5 min. Finally,
hydrogen gas was passed over the solution overnight.
The mixture was warmed, ®ltered, concentrated in-
vacuo and recrystallized from methanol and diethyl
ether.
-
1510, 1450, 1398, 1309, 1263, 750 cm
;
1H NMR
(DMSO-d6): d ¯ 1.7 (m, 2H, CH2CH2CONH), 2.15 (t,
2H, CH2CONH), 2.25 (s, 3H, CH3), 2.5 (t, 2H, CH2),
3.45 (s, 3H, NCH3), 4.45 (d, 2H, HNCH2, J¯ 6 Hz),
6.15 (s, 1H, H5), 8.15 (t, 1H, HN, J ¯ 6 Hz), 6.7±7.05
(m, 4H, aromatic), 8.15 (t, 1H, HN, J ¯ 6 Hz) ppm. MS
}
(accurate mass, high resolution, FAB): Actual. m z¯
1,6 - Dimethyl-2-(2-hydroxybenzamido)methyl-3-hydroxy-
4(1H)-pyridinone (14a) Yield 35% ; m.p. 221±
223°C; IR (KCl): 3244, 2568, 1545, 1489, 1450,
+
+
}
331.1658 (M ). Measured. m z¯ 331.1664 (M ); Anal.
Calcd for C18H22N2O4 [ 14CH3OH: C, 64.8; H, 6.9; N,
8.3% . Found: C, 64.6; H, 6.8; N, 8.2% .
1
1
-
1372, 1252, 753 cm ; H NMR (DMSO-d6): d ¯ 2.57
(s, 3H, CH3), 3.95 (s, 3H, NCH3), 4.85 (d, 2H, HNCH2,
J ¯ 5 Hz), 6.88±6.98 (m, 2H, aromatic), 7.24 (s, 1H, H5), Carboxylate-type of 3-hydroxypyridin-4-one (15)
7.39 (m, 1H, aromatic-H para to carbonyl), 7.9 (m, 1H, 1,6-Dimethyl-2-(benzylsuccinamido)methyl-3-benzyloxy-
aromatic-H ortho to carbonyl), 9.28 (t, 1H, NH, J ¯ 4(1H)-pyridinone The general method was the same
5 Hz), 12.08 (s, broad, 1H, OH) ppm. MS (accurate as that for compound 14. The compound (yield 99% )
1
}
mass, high resolution, FAB): Actual. m z ¯ 289.1188 was separated as an oil. H NMR (CDCl3): d ¯ 2.2