K. Jiang et al. / European Journal of Medicinal Chemistry 194 (2020) 112252
9
(DMSO‑d6):
d
171.88, 157.81, 129.73, 129.73, 129.73, 124.52, 116.68,
51.8%. 1H NMR (400 MHz, DMSO‑d6):
d
10.18 (s, 1H), 7.24 (t,
116.68, 68.22, 62.05, 46.35, 33.36, 28.93, 28.63, 25.68, 25.20. HRMS
(ESI) m/z: calcd. for C16H21ClN2O4 [M þ H]þ: 341.1268, found:
341.1264.
J ¼ 8.0 Hz, 1H), 7.19-7.12 (m, 1H), 6.93 (t, J ¼ 8.0 Hz, 2H), 4.32 (t,
J ¼ 8.0 Hz, 2H), 4.00 (t, J ¼ 8.0 Hz, 2H), 3.63 (t, J ¼ 8.0 Hz, 2H), 2.46 (t,
J ¼ 8.0 Hz, 2H), 1.94-1.92 (m, 2H). 13C NMR (DMSO‑d6):
d 171.36,
164.75, 162.32, 161.22, 157.66, 99.33, 99.05, 96.58, 68.07, 62.11,
46.38, 29.77, 24.50. HRMS (ESI) m/z: calcd. for C13H14F2N2O4 [M þ
H]þ: 301.1000, found: 301.0098.
5.1.1.8. Synthesis of 5-(3-fluorophenoxy)-N-(2-oxooxazolidin-3-yl)
pentanamide
(YXL-8). Ethyl
4-bromobutyrate
ethyl
5-
bromopentanoate was replaced, the p-fluorophenol was replaced
with a 2-fluorophenol moiety, and the other steps were similar to
those followed during the synthesis of YXL-1. The compound YXL-8
was obtained as a white solid weighing 0.45 g at a yield of 37.3%. 1H
5.1.1.13. Synthesis of 4-(4-bromophenoxy)-N-(2-oxooxazolidin-3-yl)
butanamide (YXL-13). In this case the p-fluorophenol moiety was
replaced with a p-bromophenol moiety, and the other steps were
similar to those followed during the synthesis of YXL-1. The com-
pound YXL-13 was obtained as a white solid weighing 0.61 g at a
NMR (400 MHz, DMSO‑d6)
d
10.10 (s, 1H), 7.08 (t, J ¼ 8.0 Hz, 2H),
6.93-6.89 (m, 2H), 4.31 (t, J ¼ 8.0 Hz, 2H), 3.90 (t, J ¼ 8.0 Hz, 2H),
3.62 (t, J ¼ 8.0 Hz, 2H), 2.47 (t, J ¼ 8.0 Hz, 2H), 2.11-1.65 (m, 4H). 13
C
yield of 56.1%. 1H NMR (400 MHz, DMSO‑d6):
d 10.17 (s, 1H), 7.41 (d,
NMR (DMSO‑d6):
d
171.44, 162.35, 160.72, 157.65, 131.21, 111.37,
J ¼ 8.0 Hz, 2H), 6.87 (d, J ¼ 8.0 Hz, 2H), 4.32 (t, J ¼ 8.0 Hz, 2H), 3.93
107.63, 102.53, 67.99, 62.07, 46.37,33.02, 28.36, 21.93. HRMS (ESI)
(t, J ¼ 8.0 Hz, 2H), 3.61 (t, J ¼ 8.0 Hz, 2H), 2.26 (t, J ¼ 8.0 Hz, 2H),1.97-
m/z: calcd. for C14H17FN2O4 [M þ H]þ: 297.1251, found: 297.1248.
1.87 (m, 2H). 13C NMR (DMSO‑d6):
d 171.43, 158.31, 157.64, 132.65,
117.28, 112.40, 67.37, 62.10, 46.38, 29.88, 24.74. HRMS (ESI) m/z:
5.1.1.9. Synthesis of 5-(4-fluorophenoxy)-N-(2-oxooxazolidin-3-yl)
calcd. for C13H15BrN2O4 [M þ H]þ: 343.0293, found: 343.0290.
pentanamide
(YXL-9). Ethyl
4-bromobutyrate
ethyl
5-
bromopentanoate was replaced, the p-fluorophenol moiety was
replaced with a 2-fluorophenol moiety, and the other steps were
similar to those followed during the synthesis of YXL-1. The com-
pound YXL-9 was obtained as a white solid weighing 0.62 g at a
5.1.1.14. Synthesis of 7-(4-bromophenoxy)-N-(2-oxooxazolidin-3-yl)
heptanamide (YXL-14). Ethyl 4-bromobutyrate was replaced with
ethyl 7-bromoheptanoate, p-fluorophenol was replaced with p-
bromophenol, and the other steps were similar to those followed
during the synthesis of YXL-1. The compound YXL-14 was obtained
as a white solid weighing 0.69 g at a yield of 59.3%. 1H NMR
yield of 57.6%. 1H NMR (400 MHz, DMSO‑d6)
d 10.10 (s, 1H), 7.07 (d,
J ¼ 8.0 Hz, 1H), 6.69e6.75 (m, 3H), 4.31 (t, J ¼ 8.0 Hz, 2H), 3.90 (t,
J ¼ 8.0 Hz, 2H), 3.62 (t, J ¼ 8.0 Hz, 2H), 2.47 (t, J ¼ 8.0 Hz, 2H), 2.11-
(400 MHz, DMSO‑d6):
d
10.08 (s,1H), 7.40 (d, J ¼ 8.0 Hz, 2H), 6.92 (d,
1.65 (m, 4H). 13C NMR (DMSO‑d6):
d
171.74, 164.76, 162.34, 160.71,
J ¼ 8.0 Hz, 2H), 4.31 (t, J ¼ 8.0 Hz, 2H), 3.90 (t, J ¼ 8.0 Hz, 2H), 3.60 (t,
J ¼ 8.0 Hz, 2H), 2.09 (t, J ¼ 8.0 Hz, 2H), 1.65-1.63 (m, 2H), 1.49-1.36
(m, 2H), 1.35-1.30 (m, 2H),1.29-1.28 (m, 2H). 13C NMR (DMSO‑d6):
157.66, 131.23, 111.38, 107.68, 102.52, 67.98, 62.08, 46.38, 33.01,
28.36, 21.94. HRMS (ESI) m/z: calcd. for C14H17FN2O4 [M þ H]þ:
297.1251, found: 297.1248.
d
171.88, 158.48, 157.65, 132.62, 132.62, 117.24, 117.24, 112.22, 62.05,
46.35, 33.36, 28.91, 28.62, 25.67, 25.20. HRMS (ESI) m/z: calcd. for
5.1.1.10. Synthesis of 4-(2,4-difluorophenoxy)-N-(2-oxooxazolidin-3-
yl)butanamide (YXL-10). The p-fluorophenol moiety was replaced
with a 2,4-difluorophenol moiety, and the other steps were similar
to those followed during the synthesis of YXL-1. The compound
YXL-10 is obtained as a white solid weighing 0.59 g at a yield of
C
16H21BrN2O4 [M þ H]þ: 385.0763, found: 385.0760.
5.1.1.15. Synthesis of 4-(4-nitrophenoxy)-N-(2-oxooxazolidin-3-yl)
butanamide (YXL-15). In this case p-fluorophenol was replaced
with p-nitrophenol, and the other steps were similar to those fol-
lowed during the synthesis of YXL-1. The compound YXL-15 was
obtained as a yellowish solid weighing 0.66 g at a yield of 52.8%. 1H
49.9%. 1H NMR (400 MHz, DMSO‑d6):
d 10.18 (s, 1H), 7.24 (t,
J ¼ 8.0 Hz, 1H), 7.19-7.12 (m, 1H), 6.93 (t, J ¼ 8.0 Hz, 2H), 4.32 (t,
J ¼ 8.0 Hz, 2H), 4.00 (t, J ¼ 8.0 Hz, 2H), 3.63 (t, J ¼ 8.0 Hz, 2H), 2.46 (t,
NMR (400 MHz, DMSO‑d6):
d
10.17 (s, 1H), 7.29 (d, J ¼ 8.0 Hz, 2H),
J ¼ 8.0 Hz, 2H), 1.94-1.92 (m, 2H). 13C NMR (DMSO‑d6):
d
171.39,
6.93 (d, J ¼ 8.0 Hz, 2H), 4.34 (t, J ¼ 8.0 Hz, 2H), 3.95 (t, J ¼ 8.0 Hz,
157.67, 154.87, 153.11, 143.67, 116.27, 111.44, 105.29, 68.84, 62.11,
46.37, 29.75, 24.79. HRMS (ESI) m/z: calcd. for C13H14F2N2O4 [M þ
H]þ: 301.1000, found: 301.0098.
2H), 3.63 (t, J ¼ 8.0 Hz, 2H), 2.29 (t, J ¼ 8.0 Hz, 2H), 2.00-1.93 (m,
2H). 13C NMR (DMSO‑d6):
d 171.88, 164.57, 157.66, 141.17, 126.43,
126.43, 115.49, 115.49, 69.07, 62.06, 46.36, 33.34, 25.17. HRMS (ESI)
m/z: calcd. for C13H15N3O6 [M þ H]þ: 310.1039, found: 310.1035.
5.1.1.11. Synthesis of 7-(2,4-dibromophenoxy)-N-(2-oxooxazolidin-3-
yl)heptanamid (YXL-11). In this case ethyl 4-bromobutyrate was
replaced with ethyl 7-bromoheptanoate, and p-fluorophenol was
replaced with 2,4-difluorophenol. The other steps of this procedure
were similar to those followed during the synthesis of YXL-1. The
compound YXL-11 was obtained as a white solid weighing 0.58 g at
5.1.1.16. Synthesis of 7-(4-nitrophenoxy)-N-(2-oxooxazolidin-3-yl)
heptanamide (YXL-16). The ethyl 4-bromobutyrate moiety was
replaced with an ethyl 7-bromoheptanoate moiety, the p-fluo-
rophenol moiety was replaced with a p-nitrophenol moiety, and
the other steps were similar to those employed during the syn-
thesis of YXL-1. The compound YXL-16 was obtained as a white
solid weighing 0.58 g at a yield of 54.9%. 1H NMR (400 MHz,
a yield of 45.2%. 1H NMR (400 MHz, DMSO‑d6):
d 10.12 (s, 1H), 7.46
(d, J ¼ 8.0 Hz, 2H), 7.03 (d, J ¼ 8.0 Hz, 2H), 4.31 (t, J ¼ 8.0 Hz, 2H),
3.99 (t, J ¼ 8.0 Hz, 2H), 3.59 (t, J ¼ 8.0 Hz, 2H), 3.59 (d, J ¼ 8.0 Hz,
2H), 1.93-1.87 (m, 2H), 1.70-1.65 (m, 2H), 1.54-1.48 (m, 2H), 1.46-
DMSO‑d6):
d
10.08 (s, 1H), 7.28 (d, J ¼ 8.0 Hz, 2H), 6.92 (d, J ¼ 8.0 Hz,
2H), 4.33 (t, J ¼ 8.0 Hz, 2H), 3.92 (t, J ¼ 8.0 Hz, 2H), 3.62 (t, J ¼ 8.0 Hz,
1.38 (m, 2H). 13C NMR (DMSO‑d6):
d 171.89, 159.18, 154.90, 135.09,
2H), 2.11 (t, J ¼ 8.0 Hz, 2H), 1.65-1.63 (m, 2H), 1.49-1.36 (m, 2H),
132.13, 115.84, 112.72, 112.46, 69.34, 61.05, 49.06, 33.37, 28.75,
28.55, 25.64, 25.21. HRMS (ESI) m/z: calcd. for C16H20Br2N2O4 [M þ
H]þ: 464.9848, found: 464.9808.
1.35-1.30 (m, 2H),1.29-1.28 (m, 2H). 13C NMR (DMSO‑d6):
d 171.87,
164.57, 157.64, 141.19, 126.41, 126.41, 115.48, 115.48, 69.07, 62.05,
46.36, 33.35, 28.73, 28.57, 25.56, 25.16. HRMS (ESI) m/z: calcd. for
C
16H21N3O6 [M þ H]þ: 352.1509, found: 352.1507.
5.1.1.12. Synthesis of 4-(3,5-difluorophenoxy)-N-(2-oxooxazolidin-3-
yl)butanamide (YXL-12). In this case the p-fluorophenol moiety
was replaced with 3,5-difluorophenol, and other steps were similar
to those followed during the synthesis of YXL-1. The compound
YXL-12 was obtained as a white solid weighing 0.62 g at a yield of
5.1.1.17. Synthesis of 4-((4-chlorophenyl)thio)-N-(2-oxooxazolidin-3-
yl)butanamide (YXL-17). In this case the p-fluorophenol was
replaced with a p-chlorothiophenol moiety, and the other steps
were similar to those followed during the synthesis of YXL-1. The