O.A. Phillips et al. / European Journal of Medicinal Chemistry 44 (2009) 3217–3227
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5.2.10. Ethyl 4-(2-fluoro-4-((R)-5-((4-methyl-1H-1,2,3-triazol-1-
yl)methyl)-2-oxooxazolidin-3-yl)phenyl)piperazine-1-
carboxylate (17f)
n 2927, 2891, 2975, 1747, 1642, 1622, 1518, 1417, 1331, 1230. MS 444
(Mþ). Anal Calcd for C22H29FN6O3: C: 59.45, H: 6.58, N: 18.91. Found
C: 59.85, H: 6.92, N: 18.29.
Recrystallization (EtOAc) gave off-white crystals (833 mg, 92%
yield), m.p. 143–145 ꢀC. 1H NMR (DMSO-d6, 600 MHz):
d
7.87 (s,
5.2.15. (R)-3-(4-(4-(3-Methylbutanoyl)piperazin-1-yl)-3-
fluorophenyl)-5-((4-methyl-1H-1,2,3-triazol-1-
yl)methyl)oxazolidin-2-one (17k)
1H), 7.43 (dd, 1H, J ¼ 2.3 Hz, 14.6 Hz), 7.14 (dd, 1H, J ¼ 2.2 Hz,
10.8 Hz), 7.07 (t, 1H, J ¼ 9.4 Hz), 5.05–5.10 (m, 1H), 4.74 (d, 2H,
J ¼ 5.1 Hz), 4.19 (t, 1H, J ¼ 9.3 Hz), 4.07 (dd, 2H, J ¼ 7.06 Hz, 14.1 Hz),
3.84 (dd, 1H, J ¼ 5.9 Hz, 9.2 Hz), 3.48–3.55 (br s, 4H), 2.94 (t, 4H,
J ¼ 4.58 Hz), 2.23 (s, 3H), 1.21 (t, 3H, J ¼ 7.0 Hz). IR (KBr pellet,
Recrystallization (EtOAc–Hex) gave crystalline solid (671 mg, 72%
yield), m.p. 173–175 ꢀC. 1H NMR (DMSO-d6, 600 MHz):
d 7.86 (s, 1H),
7.43 (dd, 1H, J ¼ 2.5 Hz, 14.7 Hz), 7.13 (dd, 1H, J ¼ 2.5 Hz, 9.0 Hz), 7.06
(t, 1H, J ¼ 9.0 Hz), 5.06–5.10 (m, 1H), 4.74 (d, 2H, J ¼ 5.2 Hz), 4.19 (t,
1H, J ¼ 9.0 Hz), 3.83 (dd, 1H, J ¼ 5.9 Hz, 9.0 Hz), 3.60 (d, 4H,
J ¼ 4.0 Hz), 2.95 (t, 2H, J ¼ 4.7 Hz), 2.90 (t, 2H, J ¼ 4.7 Hz), 2.23 (d, 2H,
overlaps with singlet at 2.22 ppm), 2.22 (s, 3H, overlaps with CH2
doublet at 2.23 ppm), 1.98–2.03 (m, 1H), 0.91 (d, 6H, J ¼ 6.7 Hz). IR
cmꢁ1):
n 2953, 2904, 1700, 1739, 1518, 1427, 1379, 1338, 1327, 1284,
1233. MS 432 (Mþ). Anal Calcd for C20H25FN6O4: C: 55.55, H: 5.83,
N: 19.73. Found C: 55.60, H: 6.27, N: 19.55.
5.2.11. S-Ethyl 4-(2-fluoro-4-((R)-5-((4-methyl-1H-1,2,3-triazol-1-
yl)methyl)-2-oxooxazolidin-3-yl)phenyl)piperazine-1-
carbothioate (17g)
(KBr pellet, cmꢁ1):
n 2868, 2956, 1741, 1630, 1520, 1442, 1420, 1325,
1223. MS 444 (Mþ). Anal Calcd for C22H29FN6O3: C: 59.45, H: 6.58, N:
18.91. Found C: 59.35, H: 6.43, N: 18.60.
Recrystallization (EtOAc) gave a crystalline solid (433 mg, 46%
yield), m.p. 180–182 ꢀC. 1H NMR (DMSO-d6, 600 MHz):
d 7.86 (s,
1H), 7.43 (dd, 1H, J ¼ 2.3 Hz, 14.7 Hz), 7.14 (dd, 1H, J ¼ 2.3 Hz,
9.0 Hz), 7.07 (t, 1H, J ¼ 9.0 Hz), 5.05–5.10 (m, 1H), 4.73 (d, 2H,
J ¼ 5.0 Hz), 4.19 (t, 1H, J ¼ 9.0 Hz), 3.84 (dd, 1H, J ¼ 5.9 Hz, 9.0 Hz),
3.54–3.66 (br s, 4H), 2.97 (t, 4H, J ¼ 4.7 Hz), 2.85 (q, 2H, J ¼ 7.3 Hz),
5.2.16. (R)-3-(4-(4-(2-Methylbutanoyl)piperazin-1-yl)-3-
fluorophenyl)-5-((4-methyl-1H-1,2,3-triazol-1-
yl)methyl)oxazolidin-2-one (17l)
Recrystallization (EtOAc–Hex) gave crystalline solid (670 mg,
2.22 (s, 3H), 1.21 (t, 3H, J ¼ 7.3 Hz). IR (KBr pellet, cmꢁ1):
n
2864,
72% yield), m.p.158–160 ꢀC. 1H NMR (DMSO-d6, 600 MHz):
d 7.86 (s,
2965, 1762, 1661, 1641, 1517, 1440, 1413, 1333, 1223. MS 448 (Mþ).
Anal Calcd for C20H25FN6O3S: C: 53.56, H: 5.62, N: 18.74. Found C:
53.20, H: 5.66, N: 18.34.
1H), 7.44 (dd, 1H, J ¼ 2.5 Hz, 14.7 Hz), 7.13 (dd, 1H, J ¼ 2.4 Hz,
9.0 Hz), 7.07 (t, 1H, J ¼ 9.4 Hz), 5.06–5.09 (m, 1H) 4.74 (d, 2H,
J ¼ 5.2 Hz), 4.19 (t, 1H, J ¼ 9.2 Hz), 3.83 (dd, 1H, J ¼ 5.9 Hz, 9.3 Hz),
3.63–3.67 (m, 4H), 2.92–2.96 (m, 4H), 2.70–2.78 (m, 1H), 2.22 (s,
3H), 1.54–1.59 (m, 1H), 1.28–1.36 (m, 1H), 1.00 (d, 3H, J ¼ 6.8 Hz),
5.2.12. (R)-3-(4-(4-(2,2-Dichloroacetyl)piperazin-1-yl)-3-
fluorophenyl)-5-((4-methyl-1H-1,2,3-triazol-1-
yl)methyl)oxazolidin-2-one (17h)
0.83 (t, 3H, J ¼ 7.4 Hz). IR (KBr pellet, cmꢁ1):
n 2933, 2970, 2827,
1749, 1639, 1519, 1471, 1444, 1424, 1337, 1225. MS 444.3 (Mþ). Anal
Calcd for C22H29FN6O3: C: 59.45, H: 6.58, N: 18.91. Found C: 59.65,
H: 6.74, N: 19.03.
Recrystallization (EtOAc) gave a crystalline solid (643 mg, 65%
yield), m.p. 102–104 ꢀC. 1H NMR (DMSO-d6, 600 MHz):
d 7.86 (s,
1H), 7.42 (dd, 1H, J ¼ 2.5 Hz, 14.7 Hz), 7.31 (s, 1H), 7.13 (dd, 1H,
J ¼ 2.5 Hz, 9.0 Hz), 7.08 (t, 1H, J ¼ 9.0 Hz), 5.06–5.09 (m, 1H), 4.73 (d,
2H, J ¼ 5.3 Hz), 4.19 (t, 1H, J ¼ 9.0 Hz), 3.85 (dd, 1H, J ¼ 5.09 Hz,
9.0 Hz), 3.70 (t, 2H, J ¼ 4.7 Hz), 3.67 (t, 2H, J ¼ 4.7 Hz), 3.02 (t, 2H,
J ¼ 4.7 Hz), 2.99 (t, 2H, J ¼ 4.7 Hz), 2.22 (s, 3H). IR (KBr pellet, cmꢁ1):
5.2.17. (R)-3-(3-Fluoro-4-(4-hexanoylpiperazin-1-yl)phenyl)-5-
((4-methyl-1H-1,2,3-triazol-1-yl)methyl)oxazolidin-2-one (17m)
Recrystallization (CH3CN) gave solid (567 mg, 58% yield), m.p.
189–190 ꢀC. 1H NMR (DMSO-d6, 600 MHz):
d 7.86 (d, 1H), 7.43
n
2948, 2828, 1755, 1669, 1518, 1445, 1420, 1329, 1231. MS 471.3
(dd, 1H, J ¼ 2.5 Hz, 14.7 Hz), 7.13 (dd, 1H, J ¼ 2.5 Hz, 9.0 Hz), 7.04
(t, 1H, J ¼ 9.0 Hz), 5.07–5.09 (m, 1H), 4.73 (d, 2H, J ¼ 5.0 Hz), 4.19
(t, 1H, J ¼ 9.0 Hz), 3.83 (dd, 1H, J ¼ 5.9 Hz, 9.0 Hz), 3.58 (br s, 4H),
2.96 (t, 2H, J ¼ 4.7 Hz), 2.90 (t, 2H, J ¼ 4.7 Hz), 2.33 (t, 2H, J ¼ 7.6 Hz),
(Mþ). Anal Calcd for C19H21Cl2FN6O3: C: 48.42, H: 4.49, N: 17.83.
Found C: 47.72, H: 4.56, N: 16.91.
5.2.13. (R)-3-(3-Fluoro-4-(4-(isobutyryl)piperazin-1-yl)phenyl)-5-
((4-methyl-1H-1,2,3-triazol-1-yl)methyl)oxazolidin-2-one (17i)
Recrystallization (EtOAc–Hex) gave a crystalline solid (629 mg,
2.22 (s, 3H), 1.26–1.51 (m, 9H). IR (KBr pellet, cmꢁ1):
n 2856, 2953,
1746, 1641, 1624, 1516, 1466, 1438, 1481, 1416, 1328, 1344, 1226. MS
458.3 (Mþ). Anal Calcd for C23H31FN6O3: C: 60.25, H: 6.81, N, 18.33,
Found C: 60.16, H: 6.96, N: 18.48.
70% yield), m.p.175–177 ꢀC. 1H NMR (DMSO-d6, 400 MHz):
d 7.86 (s,
1H), 7.43 (dd, 1H, J ¼ 2.5 Hz, 14.7 Hz), 7.28 (dd, 1H, J ¼ 2.5 Hz,
9.0 Hz), 7.07 (t, 1H, J ¼ 9.0 Hz), 5.06–5.10 (m, 1H), 4.74 (d, 2H,
J ¼ 5.3 Hz), 4.19 (t, 1H, J ¼ 9.0 Hz), 3.83 (br dd, 1H, J ¼ 5.9 Hz, 9.0 Hz),
3.64 (t, 2H, J ¼ 4.7 Hz), 3.61 (t, 2H, J ¼ 4.7 Hz), 2.97 (t, 2H, J ¼ 4.7 Hz),
2.88–2.93 (m, 3H), 2.22 (s, 3H),1.01 (d, 6H, J ¼ 6.7 Hz). IR (KBr pellet,
5.2.18. (R)-3-(3-Fluoro-4-(4-heptanoylpiperazin-1-yl)phenyl)-5-
((4-methyl-1H-1,2,3-triazol-1-yl)methyl)oxazolidin-2-one (17n)
Recrystallization (EtOAc–Hex) gave crystalline solid (914 mg, 92%
yield), m.p. 173–175 ꢀC. 1H NMR (DMSO-d6, 600 MHz):
d 7.86 (s, 1H),
cmꢁ1):
n
2970, 2832, 1756, 1637, 1518, 1477, 1416, 1438, 1338, 1229.
7.43 (dd, 1H, J ¼ 2.5 Hz, 14.7 Hz), 7.13 (dd, 1H, J ¼ 2.5 Hz, 9.0 Hz), 7.06
(t, 1H, J ¼ 9.5 Hz), 5.07–5.09 (m, 1H), 4.74 (d, 2H, J ¼ 5.2 Hz), 4.19
(t,1H, J ¼ 9.0 Hz), 3.83 (dd,1H, J ¼ 5.9 Hz, 9.0 Hz), 3.59 (br s, 4H), 2.95
(t, 2H, J ¼ 4.7 Hz), 2.90 (t, 2H, J ¼ 4.7 Hz), 2.33 (t, 2H, J ¼ 7.4 Hz), 22.2
(s, 3H), 1.48–1.51 (m, 2H), 1.25–1.30 (m, 6H), 0.86 (t, 3H, J ¼ 6.8 Hz).
MS 430 (Mþ). Anal Calcd for C21H27FN6O3: C: 58.59, H: 6.32,
N: 19.52. Found C: 58.52, H: 6.33, N: 19.26.
5.2.14. (R)-3-(3-Fluoro-4-(4-pentanoylpiperazin-1-yl)phenyl)-5-
((4-methyl-1H-1,2,3-triazol-1-yl)methyl)oxazolidin-2-one (17j)
Recrystallization (EtOAc–Hex) gave crystalline solid (629 mg,
IR (KBr pellet, cmꢁ1):
n 2857, 2925, 1745, 1631, 1517, 1478, 1428, 1417,
1343, 1328, 1226. MS 472.4 (Mþ). Anal Calcd for C24H33FN6O3:
C: 61.00, H: 7.04, N: 17.18. Found C: 60.62, H: 7.21, N: 17:73.
68% yield), m.p.189–190 ꢀC. 1H NMR (DMSO-d6, 600 MHz):
d 7.86 (s,
1H), 7.43 (dd, 1H, J ¼ 2.5 Hz, 14.7 Hz), 7.13 (dd, 1H, J ¼ 2.4 Hz,
9.0 Hz), 7.06 (t, 1H, J ¼ 9.0 Hz), 5.07–5.09 (m, 1H), 4.74 (d, 2H,
J ¼ 5.2 Hz), 4.19 (t, 1H, J ¼ 9.0 Hz), 3.83 (dd, 1H, J ¼ 5.9 Hz, 9.0 Hz),
3.59 (d, 4H, J ¼ 4.0 Hz), 2.96 (br t, 2H, J ¼ 4.7 Hz), 2.90 (br t, 2H,
J ¼ 4.7 Hz), 2.34 (t, 2H, J ¼ 7.5 Hz), 2.22 (s, 3H), 1.46–1.50 (m, 2H),
1.29–1.33 (m, 2H), 0.89 (t, 3H, J ¼ 7.4 Hz). IR (KBr pellet, cmꢁ1):
5.2.19. (R)-3-(3-Fluoro-4-(4-cyclopropanecarbonyl-piperazin-1-
yl)phenyl)-5-((4-methyl-1H-1,2,3-triazol-1-yl)methyl)oxazolidin-2-
one (17o)
Recrystallization (EtOAc–Hex) gave crystalline solid (729 mg,
81% yield), m.p. 165–167 ꢀC. 1H NMR (DMSO-d6, 400 MHz):
d 7.86