479.1729. HPLC (80% methanol in water) tR = 7.724 min,
98.25%.
(3 x 50 mL), and the organic phase was dried (Na2SO4), filtered,
and concentrated to afford compounds WL-2, 5, 9, 12, 15, 17, 20.
Phenyl 3-(2-chloro-4-fluoro-3-methylbenzamido)-4-(4-
methylpiperazin-1-yl) benzoate (WL-13)
Methyl 3-(3-amino-4-fluorobenzamido)-4-(4-
methylpiperazin-1-yl) benzoate (WL-2)
o
1
o
1
m.p. 70-73 C. H NMR (300 MHz, CDCl3) δ 9.20 (s, 1H),
8.75 (s, 1H), 7.91 (dd, J = 8.3, 2.0 Hz, 1H), 7.60-7.51 (m, 1H),
7.36-7.31 (m, 3H), 7.20-7.11 (m, 3H), 7.03 (t, J = 8.5 Hz, 1H),
3.29 (br s, 4H), 3.11 (br s, 4H), 2.70 (s, 3H), 2.31 (d, J = 2.2 Hz,
3H). HRMS (ESI): calcd. for m/z C26H26ClFN3O3 [M + H]+
482.1641, found 482.1644. HPLC (90% methanol + 0.3% TEA
in water) tR = 4.925 min, 95.58%.
m.p. 218-222 C. H NMR (300 MHz, DMSO- d6) δ 9.29 (s,
1H), 8.51 (d, J = 2.0 Hz, 1H), 7.73 (dd, J = 8.4, 2.1 Hz, 1H), 7.36
(dd, J = 8.7, 2.0 Hz, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.20-7.09 (m,
2H), 5.48 (s, 2H), 3.83 (s, 3H), 2.92 (t, J = 4.4 Hz, 4H), 2.49 (t, J
= 4.4 Hz, 4H), 2.22 (s, 3H). HRMS (ESI): calcd. for m/z
C20H24FN4O3 [M + H]+ 387.1827, found 387.1818. HPLC (90%
methanol in water) tR = 3.708 min, 96.58%.
Phenyl 3-(2-chloro-4-fluoro-3-methyl-5-nitrobenzamido)-4-
(4-methylpiperazin-1-yl) benzoate (WL-14)
Methyl 3-(5-amino-2-chloro-4-fluoro-3-methylbenzamido)-4-
(4-methylpiperazin-1-yl) benzoate (WL-5)
o
1
o
1
m.p. 192-195 C. H NMR (300 MHz, DMSO- d6) δ 9.98 (s,
1H), 8.53 (d, J = 1.7 Hz, 1H), 8.37 (d, J = 7.7 Hz, 1H), 7.94 (d, J
= 1.7 Hz, 1H), 7.50-7.45 (m, 2H), 7.31-7.25 (m, 4H), 3.32 (br s,
4H), 3.05 (br s, 4H), 2.42 (d, J = 2.3 Hz, 3H), 2.21 (s, 3H).
HRMS (ESI): calcd. for m/z C26H25ClFN4O5 [M + H]+ 527.1492,
found 527.1492. HPLC (80% methanol in water) tR = 9.214 min,
97.93%.
m.p. 223-225 C. H NMR (300 MHz, DMSO- d6) δ 9.40 (s,
1H), 8.40 (s, 1H), 7.74 (d, J = 8.3 Hz, 1H), 7.22 (d, J = 8.4 Hz,
1H), 6.81 (d, J = 9.2 Hz, 1H), 5.48 (s, 2H), 3.83 (s, 3H), 2.96 (br
s, 4H), 2.45 (br s, 4H), 2.24-2.20 (m, 6H). 13C NMR (75 MHz,
DMSO- d6) δ 11.9, 45.7, 50.1, 51.9, 54.5, 112.6, 112.7, 115.6,
119.7, 123.9, 124.4, 126.7, 131.0, 132.6, 135.3, 135.5, 148.9,
165.3, 165.8. HRMS (ESI): calcd. for m/z C21H25ClFN4O3 [M +
H]+ 435.1594, found 435.1597. HPLC (90% methanol + 0.3%
TEA in water) tR = 3.868 min, 95.00%.
Cyclohexyl
methylpiperazin-1-yl) benzoate (WL-16)
3-(4-fluoro-3-nitrobenzamido)-4-(4-
Isopropyl
methylpiperazin-1-yl) benzoate (WL-9)
3-(3-amino-4-fluorobenzamido)-4-(4-
1
m.p. 245-248 oC. H NMR (300 MHz, DMSO- d6) δ 10.09 (s,
1H), 8.74 (dd, J = 7.2, 2.2 Hz, 1H), 8.47-8.43 (m, 1H), 8.32 (d, J
= 2.0 Hz, 1H), 7.85-7.76 (m, 2H), 7.31 (d, J = 8.5 Hz, 1H), 4.93
(m, 1H), 3.34 (br s, 8H), 2.79 (s, 3H), 1.86 (m, 2H), 1.74-1.72
(m, 2H), 1.56-1.50 (m, 2H), 1.43-1.36 (m, 4H). HRMS (ESI):
calcd. for m/z C25H29FN4O5 [M + H]+ 485.2195, found 485.2197.
HPLC (80% methanol in water) tR = 13.702 min, 98.11%.
o
1
m.p. 209-212 C. H NMR (300 MHz, DMSO- d6) δ 9.31 (s,
1H), 8.46 (d, J = 2.0 Hz, 1H), 7.71 (dd, J = 8.4, 2.0 Hz, 1H), 7.36
(dd, J = 8.9, 2.1 Hz, 1H), 7.26 (d, J = 8.4 Hz, 1H), 7.17-7.10 (m,
2H), 5.47 (s, 2H), 5.11 (m, 1H), 2.94 (t, J = 4.5 Hz, 4H), 2.49 (t,
J = 4.5 Hz, 4H), 2.22 (s, 3H), 1.30 (d, J = 6.2, 6H). HRMS (ESI):
calcd. for m/z C22H28FN4O3 [M + H]+ 415.214, found 415.214.
HPLC (80% methanol in water) tR = 5.699 min, 98.54%.
Cyclohexyl 3-(2-chloro-4-fluoro-3-methylbenzamido)-4-(4-
methylpiperazin-1-yl) benzoate (WL-18)
Phenyl 3-(3-amino-4-fluorobenzamido)-4-(4-methylpiperazin-
1-yl) benzoate (WL-12)
o
1
m.p. 146-148 C. H NMR (300 MHz, CDCl3) δ 9.14 (s, 1H),
8.91 (s, 1H), 7.84 (dd, J = 8.3, 1.9 Hz, 1H), 7.61-7.56 (m, 1H),
7.29 (s, 0.5H), 7.10 (t, J = 8.6 Hz, 1H), 6.95 (m, 0.5H), 5.02 (m,
1H), 3.09 (br s, 4H), 2.80 (br s, 4H), 2.50 (s, 3H), 2.39 (d, J = 2.2
Hz, 3H), 1.96-1.92 (m, 2H), 1.81-1.79 (m, 2H), 1.63-1.56 (m,
3H), 1.46-1.42 (m, 3H). HRMS (ESI): calcd. for m/z
C26H32ClFN3O3 [M + H]+ 488.2111, found 488.2117. HPLC
(80% methanol in water) tR = 19.250 min, 98.01%.
o
1
m.p. 221-223 C. H NMR (300 MHz, DMSO- d6) δ 9.37 (s,
1H), 8.62 (s, 1H), 7.90 (dd, J = 8.4, 2.1 Hz, 1H), 7.49-7.46 (m,
2H), 7.39-7.27 (m, 4H), 7.18-7.12 (m, 2H), 5.47 (s, 2H), 3.48 (br
s, 4H), 2.99 (t, J = 4.2, 4H), 2.49 (t, J = 4.2, 4H), 2.22 (s, 3H).
HRMS (ESI): calcd. for m/z C25H26FN4O3 [M + H]+ 449.1983,
found 449.1984. HPLC (80% methanol in water) tR = 6.112 min,
97.72%.
Cyclohexyl 3-(2-chloro-4-fluoro-3-methyl-5-nitrobenzamido)-
4-(4-methylpiperazin-1-yl) benzoate (WL-19)
Phenyl 3-(5-amino-2-chloro-4-fluoro-3-methylbenzamido)-4-
(4-methylpiperazin-1-yl) benzoate (WL-15)
o
1
m.p. 149-152 C. H NMR (300 MHz, DMSO- d6) δ 9.94 (s,
1H), 8.51 (s, 1H), 8.43 (d, J = 7.4 Hz, 1H), 7.79 (d, J = 8.6 Hz,
1H), 7.26 (d, J = 8.4 Hz, 1H), 4.92 (m, 1H), 3.21 (br s, 4H), 3.16
(br s, 4H), 2.66 (s, 3H), 2.42 (s, 3H), 1.85 (m, 2H), 1.71-1.70 (m,
2H), 1.55-1.22 (m, 6H). HRMS (ESI): calcd. for m/z
C26H31ClFN4O5 [M + H]+ 533.1962, found 533.1964. HPLC
(80% methanol in water) tR = 15.279 min, 98.40%.
o
1
m.p. 212-214 C. H NMR (300 MHz, DMSO- d6) δ 9.50 (s,
1H), 8.51 (s, 1H), 7.91 (d, J = 7.3 Hz, 1H), 7.49-7.44 (m, 2H),
7.33-7.25 (m, 4H), 6.83 (d, J = 9.1 Hz), 5.48 (s, 2H), 3.02 (br s,
4H), 2.49 (br s, 4H), 2.24-2.21 (m, 6H). 13C NMR (75 MHz,
DMSO- d6) δ 11.9, 45.7, 50.4, 54.5, 112.7, 115.7, 119.8, 121.9,
122.8, 123.3, 125.3, 125.9, 127.5, 129.5, 131.0, 132.6, 135.3,
135.5, 149.9, 150.7, 164.2, 165.4. HRMS (ESI): calcd. for m/z
C26H27ClFN4O3 [M + H]+ 497.175, found 497.1748. HPLC (80%
methanol in water) tR = 8.750 min, 95.05%.
Step f: General Method for the Preparation of Compounds
WL-2, 5, 9, 12, 15, 17, 20 by Reduction of the nitro of
Compounds WL-1, 4, 8, 11, 14, 16, 19.
Cyclohexyl
methylpiperazin-1-yl) benzoate (WL-17)
3-(3-amino-4-fluorobenzamido)-4-(4-
To a solution of compounds WL-1, 4, 8, 11, 14, 16, 19 (0.5
mmol) in EA (50 mL) at room temperature was added
SnCl2.2H2O (0.46g, 2.0 mmol). The resulting solution was then
refluxed with vigorous stirring for 4~8 h, and subsequently
cooled to room temperature. Following dilution with EA (100
mL) and the mixture was neutralize with saturated sodium
bicarbonate solution. Then filtered and washed residue with EA
o
1
m.p. 219-221 C. H NMR (300 MHz, DMSO- d6) δ 9.31 (s,
1H), 8.50 (d, J = 2.0 Hz, 1H), 7.72 (dd, J = 8.4, 2.1 Hz, 1H), 7.37
(dd, J = 8.9, 2.1 Hz, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.19-7.10 (m,
2H), 5.47 (s, 2H), 4.91 (m, 1H), 2.92 (t, J = 4.4 Hz, 4H), 2.49 (t,
J = 4.4 Hz, 4H), 2.22 (s, 3H), 1.88-1.83 (m, 2H), 1.70 (m, 2H),
1.55-1.35 (m, 6H). HRMS (ESI): calcd. for m/z C25H32FN4O3 [M