A. Tourteau et al. / Bioorg. Med. Chem. xxx (2013) xxx–xxx
9
TLC using the appropriate eluent (cyclohexane/EtOAc 7:3, v/v) and
recrystallized in heptane to afford the desired compounds.
4.1.5.9. N-(1-Adamantyl)-5-(2-hexyloxyphenyl)isoxazole-3-car-
boxamide (52).
Uncolorless oil (38%). 1H NMR (DMSO) d
7.88–7.86 (m, 2H), 7.50 (t, J = 8.5 Hz, 1H), 7.22 (d, J = 8.4 Hz, 1H),
7.10 (t, J = 7.6 Hz, 1H), 6.99 (s, 1H), 4.15 (t, J = 5.2 Hz, 2H), 2.12
(m, 9H), 1.83 (m, 2H), 1.65 (m, 6H), 1.44 (m, 2H), 1.31 (m, 4H),
0.87 (t, J = 6.7 Hz, 3H). LC–MS (APCI+) m/z 423.5 (MH+); Anal. Calcd
for C26H34N2O3: C, 73.90; H, 8.11; N, 6.63. Found: C, 73.77; H, 8.04;
N, 6.54.
4.1.5.1.
(44).
N-(1-Adamantyl)-5-phenylisoxazole-3-carboxamide
White solid (52%); 157 °C. 1H NMR (DMSO) d 7.92–
7.89 (m, 3H), 7.55–7.53 (m, 3H), 7.30 (s, 1H), 2.06 (m, 9H), 1.65
(m, 6H). LC–MS (APCI+) m/z 323.2 (MH+); Anal. Calcd for
C20H22N2O2: C, 74.51; H, 6.88; N, 8.69. Found: C, 74.28; H, 6.65;
N, 8.52.
4.1.5.10.
carboxamide (53).
N-(1-Adamantyl)-5-(2-heptyloxyphenyl)isoxazole-3-
White solid (26%); mp 88 °C. 1H NMR
4.1.5.2.
(45).
N-(2-Adamantyl)-5-phenylisoxazole-3-carboxamide
White solid (51%); mp 158 °C. 1H NMR (DMSO) d 8.36
(DMSO) d 7.88 (s, 1H), 7.87 (dd, J = 7.9, 1.7 Hz, 1H), 7.50 (t,
J = 7.9 Hz, 1H), 7.23 (d, J = 8.5 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 6.99
(s, 1H), 4.15 (t, J = 6.4 Hz, 2H), 2.05 (m, 9H), 1.82 (m, 2H), 1.65 (s,
6H), 1.48–1.27 (m, 8H), 0.86 (t, J = 6.8 Hz, 3H). LC–MS (APCI+) m/z
437.3 (MH+); Anal. Calcd for C27H36N2O3: C, 74.28; H, 8.31; N,
6.42. Found: C, 74.17; H, 8.29; N, 6.31.
(d, J = 6.4 Hz, 1H), 8.27 (d, J = 7.6 Hz, 1H), 7.95 (t, J = 8.2 Hz, 1H),
7.53 (d, J = 8.2 Hz, 1H), 7.34 (t, J = 7.8 Hz, 1H), 7.29–7.26 (m, 2H),
4.09 (d, J = 5.3 Hz, 1H), 2.63 (m, 9H), 1.84 (m, 5H). LC–MS (APCI+)
m/z 323.1 (MH+); Anal. Calcd for C20H22N2O2: C, 74.51; H, 6.88;
N, 8.69. Found: C, 74.32; H, 6.72; N, 8.56.
4.1.5.3. N-(1-Adamantylmethyl)-5-phenylisoxazole-3-carbox-
amide (46).
4.1.5.11. N-(1-Adamantyl)-5-(2-octyloxyphenyl)isoxazole-3-car-
boxamide (54).
White solid (34%); mp 166 °C. 1H NMR (DMSO)
White solid (14%); mp 88 °C. 1H NMR (DMSO)
d 8.60 (t, J = 6.1 Hz, 1H), 7.93–7.91 (m, 2H), 7.56–7.53 (m, 3H),
7.35 (s, 1H), 2.97 (d, J = 6.4 Hz, 2H), 1.92 (m, 3H), 1.68–1.49 (m,
12H). LC–MS (APCI+) m/z 337.3 (MH+); Anal. Calcd for
d 7.87 (dd, J = 7.9, 1.7 Hz, 1H), 7.85 (s, 1H), 7.50 (t, J = 7.9 Hz, 1H),
7.23 (d, J = 8.5 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 6.99 (s, 1H), 4.15
(t, J = 6.4 Hz, 2H), 2.05 (m, 9H), 1.82 (m, 2H), 1.65 (s, 6H), 1.48–
1.25 (m, 10H), 0.85 (t, J = 7.0 Hz, 3H). LC–MS (APCI+) m/z 451.3
(MH+); Anal. Calcd for C28H38N2O3: C, 74.63; H, 8.50; N, 6.22.
Found: C, 74.47; H, 8.19; N, 6.08.
C21H24N2O2: C, 74.97; H, 7.19; N, 8.33. Found: C, 74.84; H, 7.04;
N, 8.19.
4.1.5.4. N-(1-Adamantyl)-5-(2-methoxyphenyl)isoxazole-3-car-
boxamide (47).
White solid (13%); mp 102 °C. 1H NMR
4.1.5.12. N-(1-Adamantyl)-5-(3-pentyloxyphenyl)isoxazole-3-
carboxamide (55).
(DMSO) d 7.88–7.86 (m, 2H), 7.53 (t, J = 7.0 Hz, 1H), 7.23 (d,
J = 8.4 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 7.04 (s, 1H), 3.96 (s, 3H),
2.06 (m, 9H), 1.65 (m, 6H). LC–MS (APCI+) m/z 353.2 (MH+); Anal.
Calcd for C21H24N2O3: C, 71.57; H, 6.86; N, 7.95. Found: C, 71.52;
H, 6.78; N, 7.92.
White solid (59%); mp 109 °C. 1H NMR
(DMSO) d 7.87 (s, 1H), 7.44 (m, 3H), 7.34 (s, 1H), 7.08 (d,
J = 8.2 Hz, 1H), 4.04 (t, J = 6.4 Hz, 2H), 2.05 (m, 9H), 1.73 (m, 2H),
1.65 (m, 6H), 1.42–1.32 (m, 4H), 0.90 (t, J = 6.7 Hz, 3H). LC–MS
(APCI+) m/z 409.4 (MH+); Anal. Calcd for C25H32N2O3: C, 73.50; H,
7.90; N, 6.86. Found: C, 73.42; H, 7.80; N, 6.71.
4.1.5.5.
boxamide (48).
N-(1-Adamantyl)-5-(2-ethoxyphenyl)isoxazole-3-car-
White solid (24%); mp 76 °C. 1H NMR (DMSO)
4.1.5.13. N-(1-Adamantyl)-5-(4-pentyloxyphenyl)isoxazole-3-
d 7.96 (s, 1H), 7.86 (d, J = 7.6 Hz, 1H), 7.54 (t, J = 8.4 Hz, 1H), 7.25 (d,
J = 8.4 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 7.06 (s, 1H), 4.28 (q,
J = 6.5 Hz, 2H), 2.06 (m, 9H), 1.65 (m, 6H), 0.94 (t, J = 6.7 Hz, 3H).
LC–MS (APCI+) m/z 367.6 (MH+); Anal. Calcd for C22H26N2O3: C,
72.11; H, 7.15; N, 7.64. Found: C, 72.06; H, 7.12; N, 7.59.
carboxamide (56).
White solid (47%); mp 156 °C. 1H NMR
(DMSO) d 7.83 (s, 1H), 7.80 (d, J = 8.6 Hz, 2H), 7.12 (s, 1H), 7.07
(d, J = 9.0 Hz, 2H), 4.03 (t, J = 6.4 Hz, 2H), 2.05 (m, 9H), 1.73 (m,
2H), 1.65 (m, 6H), 1.39–1.33 (m, 4H), 0.89 (t, J = 7.0 Hz, 3H). LC–
MS (APCI+) m/z 409.1 (MH+); Anal. Calcd for C25H32N2O3: C,
73.50; H, 7.90; N, 6.86. Found: C, 73.34; H, 7.71; N, 6.69.
4.1.5.6. N-(1-Adamantyl)-5-(2-propoxyphenyl)isoxazole-3-car-
boxamide (49).
White solid (29%); mp 62 °C. 1H NMR (DMSO)
4.1.5.14. N-(2-Adamantyl)-5-(2-pentyloxyphenyl)isoxazole-3-
carboxamide (57).
d 7.88–7.86 (m, 2H), 7.50 (t, J = 8.5 Hz, 1H), 7.22 (d, J = 8.5 Hz, 1H),
7.11 (t, J = 7.6 Hz, 1H), 7.00 (s, 1H), 4.13 (t, J = 6.4 Hz, 2H), 2.06 (m,
9H), 1.81 (m, 2H), 1.65 (m, 6H), 1.04 (t, J = 7.3 Hz, 3H). LC–MS
(APCI+) m/z 381.1 (MH+); Anal. Calcd for C23H28N2O3: C, 72.61; H,
7.42; N, 7.36. Found: C, 72.42; H, 7.25; N, 7.17.
White solid (32%); mp 68 °C. 1H NMR
(CDCl3) d 7.97 (dd, J = 7.9, 1.7 Hz, 1H), 7.41 (t, J = 7.9 Hz, 1H), 7.20
(s, 1H), 7.19 (s, 1H), 7.08–6.99 (m, 2H), 4.26 (m, 1H), 4.12 (t,
J = 6.7 Hz, 2H), 2.07 (s, 2H), 1.95–1.90 (m, 10H), 1.78 (s, 2H), 1.72
(s, 1H), 1.68 (s, 1H), 1.52–1.38 (m, 4H), 0.95 (t, J = 7.0 Hz, 3H).
LC–MS (APCI+) m/z 409.2 (MH+); Anal. Calcd for C25H32N2O3: C,
73.50; H, 7.90; N, 6.86. Found: C, 73.27; H, 7.72; N, 6.74.
4.1.5.7.
boxamide (50).
N-(1-Adamantyl)-5-(2-butoxyphenyl)isoxazole-3-car-
White solid (36%); mp 82 °C. 1H NMR (DMSO)
d 7.88–7.86 (m, 2H), 7.50 (t, J = 8.5 Hz, 1H), 7.24 (d, J = 8.4 Hz, 1H),
7.10 (t, J = 7.6 Hz, 1H), 6.98 (s, 1H), 4.17 (t, J = 6.4 Hz, 2H), 2.06 (m,
9H), 1.81 (m, 2H), 1.65 (m, 6H), 1.48 (m, 2H), 0.96 (t, J = 7.3 Hz, 3H).
LC–MS (APCI+) m/z 395.4 (MH+); Anal. Calcd for C24H30N2O3: C,
73.07; H, 7.66; N, 7.10. Found: C, 72.92; H, 7.58; N, 6.98.
4.1.5.15. N-(3-Noradamantyl)-5-(2-pentyloxyphenyl)isoxazole-
3-carboxamide (58).
White solid (56%); mp 101 °C. 1H NMR
(CDCl3) d 7.97 (d, J = 7.9 Hz, 1H), 7.41 (t, J = 7.9 Hz, 1H), 7.19 (s,
1H), 7.04 (m, 3H), 4.11 (t, J = 7.0 Hz, 2H), 2.60 (t, J = 6.8 Hz, 1H),
2.34 (s, 2H), 2.22 (m, 2H), 2.14–2.01 (m, 4H), 1.93 (quint,
J = 7.0 Hz, 2H), 1.70–1.59 (m, 4H), 1.49–1.35 (m, 4H), 0.95 (t,
J = 7.0 Hz, 3H). HRMS (FTMS + p ESI Full ms) m/z 395.2316 (MH+);
Anal. Calcd for C24H30N2O3: C, 73.07; H, 7.66; N, 7.10. Found: C,
72.93; H, 7.48; N, 6.87.
4.1.5.8.
carboxamide (51).
N-(1-Adamantyl)-5-(2-pentyloxyphenyl)isoxazole-3-
White solid (65%); mp 65 °C. 1H NMR
(DMSO) d 7.88–7.86 (m, 2H), 7.49 (t, J = 8.5 Hz, 1H), 7.22 (d,
J = 8.4 Hz, 1H), 7.10 (t, J = 7.6 Hz, 1H), 6.99 (s, 1H), 4.15 (t,
J = 7.0 Hz, 2H), 2.05 (m, 9H), 1.82 (m, 2H), 1.77 (m, 6H), 1.68–
1.21 (m, 4H), 0.90 (t, J = 7.0 Hz, 3H). LC–MS (APCI+) m/z 409.4
(MH+); Anal. Calcd for C25H32N2O3: C, 73.50; H, 7.90; N, 6.86.
Found: C, 73.39; H, 7.66; N, 6.57.
4.1.5.16. N-Cyclopropyl-5-(2-pentyloxyphenyl)isoxazole-3-car-
boxamide (59).
White solid (18%); mp 95 °C. 1H NMR (DMSO)
d 8.86 (d, J = 4.3 Hz, 1H), 7.88 (dd, J = 7.9, 1.7 Hz, 1H), 7.50 (t,
J = 7.9 Hz, 1H), 7.23 (d, J = 8.5 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 7.04