˘
Synthesis of linezolid-like molecules and evaluation of..., S. BAS¸OGLU, et al.
δ ppm 2.94 (brs, 4H, 2CH2), 3.72 (brs, 4H, 2CH2), 5.48 (brs, 1H, thiazole C4), 6.69-7.14 (m, 6H, arH), 7.15-
7.60 (m, 1H, arH), 7.69 (s, 1H, arH), 7.82-7.86 (m, 1H, arH), 8.13-8.17 (m, 2H, arH); 13 C-NMR (DMSO-d6):
δ ppm 50.88-51.50 (2CH2), 66.78-66.94 (2CH2), arC [110.19 (CH), 117.13 (CH), 118.25 (CH), 120.58 (2CH),
123.94 (CH), 125.79 (CH), 129.07 (2CH), 129.85 (2CH), 131.48 (C), 132.25 (C), 137.73 (C), 137.92 (C), 147.57
(C), 147.80 (C), 157.19 (C)], 120.58 (thiadiazole C4), 138.49 (thiazole C5), 149.63 (thiazole C2); MS m/z (%):
284.17 (24), 316.20 (21), 330.05 (29), 335.14 (22), 371.39 (21), 383.28 (100), 399.33 (39), 401.28 (22), 415.38
(39), 431.36 (20), 459.43 (27), 474.41 (40), 495.30 ([M+1]+ , 24), 513.23 (53), 519.40 ([M+2+Na]+ , 43), 580.31
(93); Anal. Calcd. (%) for C25 H20 F2 N4 O3 S: 60.72, C; 4.08, H; 11.33, N. Found: 60.33, C; 4.48, H; 11.30, N.
Ethyl {[3-fluoro-4-(morpholin-4-yl)phenyl]amino}acetate (7): Ethyl bromoacetate (10 mmol)
was added to a mixture of compound 2 (10 mmol) and triethylamine (10 mmol) dropwise in dry tetrahydrofuran
at 0-5 ◦ C. The reaction content was allowed to reach room temperature and was stirred for 11 h; the progress
of the reaction was monitored by TLC. The precipitated triethylammonium salt was removed by filtration.
After the solvent was evaporated under reduced pressure, a yellow solid appeared. This crude product was
recrystallized from ethyl acetate and petroleum ether (1:2) to afford the desired product (yield: 1.94 g, 69%).
Mp 85 ◦ C; IR (KBr) cm−1 : 3384 (NH), 1729 (C=O), 1117 (C-O); 1 H-NMR (DMSO-d6): δ ppm 1.16 (t, 3H,
CH3 , J = 6.6 Hz), 2.79 (brs, 4H, 2CH2), 3.66 (brs, 4H, 2CH2), 3.82 (s, 2H, NCH2), 4.07 (q, 2H, OCH2 , J =
6.6 Hz), 5.93 (brs, 1H, NH, D2 O exchange), 6.25-6.40 (m, 2H, arH), 6.81 (t, 1H, arH, J = 9.0 Hz); 13 C-NMR
(DMSO-d6): δ ppm 14.68 (CH3), 45.48 (CH2), 52.14 (2CH2), 61.18 (CH2), 66.90 (2CH2), arC [100.94 (CH),
108.45 (CH), 121.10 (CH), 130.04 (C), 145.54 (C), 154.49 (C)], 172.10 (C=O); MS m/z (%): 124.80 (43), 130.80
(100), 152.83 (64), 162.84 (42), 190.94 (37), 195.88 (68), 196.89 (54), 208.90 (38), 210.90 (23), 283.05 ([M+1]+ ,
19), 383.24 (48); Anal. Calcd. (%) for C14 H19 FN2 O3 : 59.56, C; 6.78, H; 9.92, N. Found: 59.16, C; 6.97, H;
10.32, N.
2-{[3-Fluoro-4-(morpholin-4-yl)phenyl]amino}acetohydrazide (8): Hydrazide hydrate (25 mmol)
was added to a solution of compound 7 (10 mmol) in absolute ethanol, and the mixture was allowed to reflux
for 7 h. When the reaction mixture cooled to room temperature, a white solid appeared. The crude product
was filtered off and recrystallized from ethanol to give the desired compound (yield: 1.87 g, 70%). Mp 182 ◦ C;
IR (KBr) cm−1 : 3339-3293 (NH2), 3339 (NH), 1653 (C=O); 1 H-NMR (DMSO-d6): δ ppm 2.75 (brs, 4H,
2CH2), 3.56 (brs, 4H, 2CH2), 3.88 (s, 2H, CH2), 4.25 (brs, 2H, NH2 , D2 O exchange), 5.87 (brs, 1H, NH, D2 O
exchange), 6.26-6.46 (m, 2H, arH), 6.81 (t, 1H, arH, J = 9.2 Hz), 9.11 (brs, 1H, NH, D2 O exchange); 13 C-NMR
(DMSO-d6): δ ppm 46.06 (CH2), 52.23 (2CH2), 67.04 (2CH2), arC [101.01 (CH), 108.56 (CH), 121.03 (CH),
130.13 (C), 145.82 (C), 154.06 (C)], 170.01 (C=O); MS m/z (%): 137.94 (28), 150.83 (21), 162.97 (39), 164.97
(23), 195.88 (71), 208.90 (95), 309.15 (75), 331.18 (100); Anal. Calcd. (%) for C12 H17 FN4 O2 : 53.72, C; 6.39,
H; 20.88, N. Found: 54.12, C; 6.20, H; 20.71, N.
N -(4-Fluorophenyl)-2-({[3-fluoro-4-(morpholin-4-yl)phenyl]amino}acetyl) hydrazinecarboth-
ioamide (9): A mixture of compound 8 (10 mmol) and 4-fluorophenyl isothiocyanate (10 mmol) in absolute
ethanol was refluxed for 7 h. When the reaction content cooled to room temperature, a white solid formed.
This crude product was filtered off and recrystallized from ethyl acetate to afford the desired compound (yield:
3.02 g, 61%). Mp 160 ˚C; IR (KBr) cm−1 : 3331 (2NH), 3164 (2NH), 1690 (C=O), 1226 (C=S). 1 H-NMR
(DMSO-d6): δ ppm 2.79 (brs, 4H, 2CH2), 3.41 (brs, 4H, 2CH2), 3.76 (d, 2H, CH2 , J = 5.2 Hz), 5.88 (s,
1H, NH, D2 O exchange), 6.34-6.48 (m, 2H, arH), 6.82 (t, 1H, arH, J = 9.8 Hz), 7.16 (t, 2H, arH, J = 9.0
41