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J. Azema et al. / Bioorg. Med. Chem. 14 (2006) 2569–2580
2578
CH3 of the NA moiety); 1.61 (tt, 3J = 7.0 Hz and
3J = 7.3 Hz, 2H, CH2e); 2.36 (t, 3J = 7.3 Hz, 2H,
CH2f); 2.63 (s, 3H, CH3 of the NA moiety); 4.46 (q,
3J = 7.0 Hz, 2H, CH2 of the NA moiety); 5.96 (s, 2H,
NA moiety); 22.66, 24.59, 29.03, 29.14, 29.22, 29.32,
29.43, 29.57, 29.62, 29.64, 31.90, 34.04 (CH2a–l);
46.78 (CH2 of the NA moiety); 79.45 (O–CH2–O);
110.34, 148.55, 162.84 (Cq); 121.39, 136.90, 149.16
(CH); 163.19, 172.64 (COO); 174.57 (CO). UV (CHCl3)
3
O–CH2–O); 7.25 (d, J = 7.9 Hz, 1H, CH); 8.6 (d and
s, 3J = 7.9 Hz, 2H, CH). 13C NMR (CDCl3,
75.5 MHz) d: 14.00 (CH3); 15.19, 25.05 (CH3 of the
NA moiety); 22.53, 24.56, 28.84, 28.95, 31.59, 34.01
(CH2a–/); 46.78 (CH2 of the NA moiety); 79.43 (O–
CH2–O); 110.29, 121.43, 148.53, 162.86 (Cq); 121.38,
136.85, 149.17 (CH); 163.16, 172.63 (COO); 174.57
kmax: 260 nm (e = 14124), kmax: 336 nm (e = 12180). MS
(CI/NH3) m/z 473 (MH+), 233 (MH+ꢀH2CO-
COC13H27). Anal. (C25H36N2O5Æ0.2C8H18) C, H, N:
calcd 69.33, 8.87, 5.65; found 69.37, 9.06, 5.72.
4.5.4. 3-[(Hexadecanoyloxy)methyl]1-ethyl-7-methyl-4-
(1e).
(CO). UV (CHCl3) kmax: 260 nm (e = 14740), kmax
:
oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylate
336 nm (e = 12900). MS (CI/NH3) m/z 389 (MH+), 233
(MH+ ꢀ H2COCOC7H15). Anal. (C21H28N2O5Æ0.15-
H2O) C, H, N: calcd 64.48, 7.29, 7.16; found 64.43,
7.29, 7.58.
This compound was synthesised from hexadecanoic acid
(0.091 g, 0.35 mmol) and K2CO3 (0.07 g, 0.66 mmol) in
dry DMF (2 mL). Compound 3 (0.1 g, 0.35 mmol) was
added. The remaining residue was flash chromato-
graphed on silica gel with diethyl ether to give 1e
(0.08 g, 56% yield) as a white solid.
4.5.2. 3-[(Dodecanoyloxy)methyl]1-ethyl-7-methyl-4-oxo-
1,4-dihydro-[1,8]naphthyridine-3-carboxylate (1c). This
compound was synthesised from dodecanoic acid
(0.081 g, 0.4 mmol) and K2CO3 (0.09 g, 0.85 mmol) in
dry DMF (2 mL). Compound 3 (0.1 g, 0.35 mmol) was
added. The remaining residue was flash chromato-
graphed on silica gel with diethyl ether/ethyl acetate
(98:2; v/v) to give 1c (0.08 g, 50% yield) as a white solid.
1H NMR (CDCl3, 250 MHz) d: 0.86 (t, 3J = 6.5 Hz, 3H,
3
CH3); 1.22 (m, 24H, CH2a–l); 1.48 (t, J = 7.0 Hz, 3H,
CH3 of the NA moiety); 1.62 (tt, 3J = 7.0 Hz and
3J = 7.6 Hz, 2H, CH2m); 2.36 (t, 3J = 7.6 Hz, 2H,
CH2f); 2.65 (s, 3H, CH3 of the NA moiety); 4.47 (q,
3J = 7.0 Hz, 2H, CH2 of the NA moiety); 5.98 (s, 2H,
3
O–CH2–O); 7.25 (d, J = 8.3 Hz, 1H, CH); 8.62 (d and
1H NMR (CDCl3, 250 MHz) d: 0.86 (t, 3J = 6.7 Hz, 3H,
s, 3J = 8.3 Hz, 2H, CH). 13C NMR (CDCl3,
75.5 MHz) d: 14.11 (CH3); 15.21, 25.06 (CH3 of the
NA moiety); 22.68, 24.60, 29.04, 29.23, 29.34, 29.45,
29.58, 29.64, 29.67, 31.91, 34.05 (CH2a–f); 46.79 (CH2
of the NA moiety); 79.45 (O–CH2–O); 110.35, 148.55,
162.85 (Cq); 121.40, 136.92, 149.16 (CH); 163.20,
172.66 (COO); 174.59 (CO). UV (CHCl3) kmax: 260 nm
(e = 15995), kmax: 336 nm (e = 13938). MS (CI/NH3)
m/z 205 (MH+), 233 (MH+ꢀH2COCOC15H31). Anal.
(C29H44N2O5Æ0.4H2O) C, H, N: calcd 68.58, 8.89, 5.52;
found 68.48, 8.88, 5.87.
3
CH3); 1.21 (m, 16H, CH2a–h); 1.49 (t, J = 7.0 Hz, 3H,
CH3 of the NA moiety); 1.62 (tt, 3J = 7.0 Hz and
3J = 7.6 Hz, 2H, CH2i); 2.36 (t, 3J = 7.6 Hz, 2H,
CH2j); 2.66 (s, 3H, CH3 of the NA moiety); 4.47 (q,
3
2H, J = 7.0 Hz, CH2 of the NA moiety); 5.98 (s, 2H,
O–CH2–O); 7.26 (d, 3J = 7.95 Hz, 1H, CH); 8.62 (d
and s, 3J = 7.95 Hz, 2H, CH). 13C NMR (CDCl3,
75.5 MHz) d: 14.09 (CH3); 15.21, 25.06 (CH3 of the
NA moiety); 22.66, 24.60, 29.04, 29.22, 29.30, 29.44,
29.57, 29.69, 31.89, 34.06 (CH2a–j); 46.79 (CH2 of the
NA moiety); 79.46 (O–CH2–O); 110.37, 148.57, 162.86
(Cq); 121.41, 136.94, 149.17 (CH); 163.22, 172.68
(COO); 174.61 (CO). UV (CHCl3) kmax: 260 nm
(e = 14426), kmax: 336 nm (e = 12527). MS (CI/NH3)
m/z 445 (MH+), 233 (MH+ ꢀ H2COCOC11H23). Anal.
(C25H36N2O5) C, H, N: calcd 67.54, 8.16, 6.30; found
67.78, 8.60, 6.04.
4.5.5. 3-[(4-Heptylbenzoyloxy)methyl]1-ethyl-7-methyl-4-
(1f).
oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylate
This compound was synthesised from 4-heptylbenzoic
acid (0.077 g, 0.35 mmol) and K2CO3 (0.06 g,
0.56 mmol) in dry DMF (2 mL). Compound 3 (0.1 g,
0.35 mmol) was added. The remaining residue was flash
chromatographed on silica gel with dichloromethane/
ethyl acetate/Et3N (10:2:0.1; v/v/v) to give 1f (0.094 g,
58% yield) as a white solid.
4.5.3. 3-[(Tetradecanoyloxy)methyl]1-ethyl-7-methyl-4-
oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylate (1d).
This compound was synthesised from tetradecanoic acid
(0.08 g, 0.35 mmol) and K2CO3 (0.07 g, 0.66 mmol) in
dry DMF (2 mL). Compound 3 (0.1 g, 0.35 mmol) was
added. The remaining residue was flash chromato-
graphed on silica gel with diethyl ether to give 1d
(0.1 g, 60% yield) as a white solid.
1H NMR (CDCl3, 250 MHz) d: 0.85 (t, 3J = 6.5 Hz, 3H,
CH3); 1.26 (m, 8H, CH2a–d); 1.48 (t, 3J = 7.3 Hz,
3H, CH3 of the NA moiety); 1.6 (tt, 3J = 6.7 Hz
and 3J = 7.6 Hz, 2H, CH2e); 2.65 (s and t, 3J = 7.6
Hz, 5H, CH3 of the NA moiety and CH2f); 4.48
(q, 3J = 7.3 Hz, 2H, CH2 of the NA moiety); 6.22
1H NMR (CDCl3, 250 MHz) d: 0.85 (t, 3J = 6.5 Hz, 3H,
(s, 2H, O–CH2–O); 7.21–7.26 (2d, 3JCH(aro)
=
3
CH3); 1.20 (m, 20H, CH2a–j); 1.48 (t, J = 7.0 Hz, 3H,
3JCH(NA) = 8.25 Hz, 3H, CH(aro) and CH); 7.99 (d,
3J = 8.25 Hz, 2H, CH); 8.63 (d and s, 3J = 8.25 Hz,
2H, CH). 13C NMR (CDCl3, 75.5 MHz) d: 14.05
(CH3); 15.19, 23.05 (CH3 of the NA moiety); 22.60,
29.07, 29.15, 31.06, 31.73, 36.02 (CH2a–f); 46.81 (CH2
of the NA moiety); 79.68 (O–CH2–O); 121.37, 136.84,
149.23 (CH); 110.23, 149.35, 162.84 (Cq of the NA moi-
ety); 126.50, 148.52 (Cq(aro)); 128.91, 130.16 (CH(aro));
CH3 of the NA moiety); 1.61 (tt, 3J = 7.3 Hz and
3J = 7.6 Hz, 2H, CH2k); 2.35 (t, 3J = 7.3 Hz, 2H,
CH2l); 2.64 (s, 3H, CH3 of the NA moiety); 4.47 (q,
3J = 7.0 Hz, 2H, CH2 of the NA moiety); 5.97 (s, 2H,
O–CH2–O); 7.25 (d, 3J = 8.25 Hz, 1H, CH); 8.62 (d
and s, 3J = 8.25 Hz, 2H, CH). 13C NMR (CDCl3,
75.5 MHz) d: 14.10 (CH3); 15.20, 25.05 (CH3 of the