254
X. XU ET AL.
obtain precipitate 21f (15.4 g, 85%). HRMS m/z [M þ H]þ calculated DMSO-d6) d: 10.48 (s, 1H, -NH-), 8.86 (s, 1H, -ArH), 8.67 (d,
for C9H12NOS: 182.0634, found: 182.0636.
J ¼ 6.0 Hz, 1H, -ArH), 7.62–7.56 (m, 3H, -ArH), 7.21–7.13 (m, 2H,
-ArH), 4.23 (s, 2H, -CH2-) ppm.
2-Mercapto-N-(4-methoxyphenyl)acetamide (21g). To a solution 4-
methoxyaniline (12.3 g, 0.1 mol, 1 eq) at room temperature was
added mercaptoacetic acid (10.1 g, 0.11 mol, 1.1 eq). The mixture
was then stirred at 100 ꢀC for 6 h and quenched at room tempera-
ture by addition of a saturated solution of sodium bicarbonate
then obtain precipitate 21 g (17.5 g, 89%). HRMS m/z [M þ H]þ cal-
culated for C9H12NO2S: 198.0583, found: 198.0586.
2-((2-Cyanopyridin-3-yl)thio)-N-(4-fluorophenyl)acetamide (LBJ-06).
The title compound was prepared from 3-chloro-2-cyanopyridine
and 21b following the synthesis route of LBJ-01. Yellow solid
(1.3 g, 45%). m.p. 211–213 ꢀC. HRMS m/z [M þ H]þ calculated for
C14H11FN3OS: 288.0601, found: 288.0605. 1H NMR (300 MHz,
DMSO-d6) d: 9.63 (s, 1H, -NH-), 8.70–8.68 (m, 1H, -ArH), 8.46–8.43
(m, 1H, -ArH), 7.74–7.69 (m, 2H, -ArH), 7.57–7.53 (m, 1H, -ArH), 7.18
(t, J ¼ 9.0 Hz, 2H, -ArH), 6.94 (s, 2H, -CH2-) ppm. 13C NMR (75 MHz,
DMSO-d6) d: 163.5, 158.0 (1JCF ¼ 240.0 Hz), 147.1, 146.8, 146.6,
135.1, 132.2, 131.7, 123.1 (3JCF ¼ 7.5 Hz), 122.5, 115.0
(2JCF ¼ 22.5 Hz), 42.8 ppm.
2-((3-Cyanopyridin-2-yl)oxy)-N-(4-fluorophenyl)acetamide (LBJ-01).
To a solution of 2-chloro-3-nitrile pyridine (1.4 g, 10 mmol, 1 eq)
and 21a (2.5 g, 15 mmol, 1.5 eq) in anhydrous DMF at room tem-
perature was added K2CO3 (1.4, 10 mmol, 1 eq). The mixture was
then stirred at 20 ꢀC for 15 min, the reaction was quenched with
water then the product was obtained by filtration and the precipi-
tate was purified by silica gel chromatography (PE/EA, v/v, 5:1) to
2-((3-Cyano-6-methylpyridin-2-yl)thio)-N-(4-fluorophenyl)acetamide
(LBJ-07). The title compound was prepared from 2-chloro-3-cyano-
pyridine and 21b following the synthesis route of LBþJ-01. Yellow
solid (1.4 g, 46%). m.p. 238–240 ꢀC. HRMS m/z [M þ H] calculated
for C15H13FN3OS: 302.0758, found: 302.0758. 1H NMR (300 MHz,
DMSO-d6) d: 10.39 (s, 1H, -NH-), 8.11 (d, J ¼ 9.0 Hz, 1H, -ArH),
7.61–7.57 (m, 2H, -ArH), 7.20–7.13 (m, 3H, -ArH), 4.17 (s, 2H, -CH2-),
2.5 (s, 3H, -CH3) ppm.
give the title product as
a white solid (1.2 g, 43%). m.p.
234–236 ꢀC. HRMS m/z [M þ Na]þ calculated for C14H10FN3OSNa:
294.0655, found: 294.0659. 1H NMR (300 MHz, DMSO-d6) d: 10.27
(s, 1H, -NH-), 8.42 (d, J ¼ 3.3 Hz, 1H, -ArH), 8.33 (d, J ¼ 6.73 Hz, 1H,
-ArH), 7.58 (s, 2H, -ArH), 7.24–7.12 (m, 3H, -ArH), 5.09 (s, 2H, -CH2-)
ppm. 13C NMR (75 MHz, DMSO-d6) d: 165.6, 162.5, 158.0
(1JCF ¼ 240.0 Hz), 151.5, 144.2, 134.9, 134.8, 120.9 (3JCF ¼ 8.3 Hz),
117.8, 115.4 (2JCF ¼ 22.5 Hz), 95.7, 64.7 ppm.
2-((3-Cyano-6-(trifluoromethyl)pyridin-2-yl)thio)-N-(4-fluorophenyl)
acetamide (LBJ-08). The title compound was prepared from 18a
and 21b following the synthesis route of LBJ-01. Yellow solid
(1.5 g, 43%). m.p. 201–204 ꢀC. HRMS m/z [M þ H]þ calculated for
C15H10F4N3OS: 356.0475, found: 356.0477. 1H NMR (300 MHz,
DMSO-d6) d: 10.42 (s, 1H, -NH-), 8.56 (d, J ¼ 6.0 Hz, 1H, -ArH), 7.82
(d, J ¼ 9.0 Hz, 1H, -ArH), 7.58–7.53 (m, 2H, -ArH), 7.15 (t, J ¼ 9.0 Hz,
2H, -ArH), 4.24 (s, 2H, -CH2-) ppm. 13C NMR (75 MHz, DMSO-d6) d:
164.0, 158.6 (1JCF ¼ 238.5 Hz), 149.0, 137.4, 135.4, 132.0, 128.0,
123.9, 122.9 (3JCF ¼ 7.5 Hz), 122.6, 114.9 (2JCF ¼ 22.5 Hz),
97.47, 30.65 ppm.
2-((2-Cyanophenyl)thio)-N-(4-fluorophenyl)acetamide (LBJ-02). The
title compound was prepared from 2-chlorobenzonitrile and 21b
following the synthesis route of LBJ-01. Yellow solid (1.1 g, 40%).
m.p. 215–217 ꢀC. HRMS m/z [M þ H]þ calculated for C15H12FN2OS:
1
287.0654, found: 287.0668. H NMR (300 MHz, DMSO-d6) d: 9.44 (s,
1H, -NH-), 8.10 (d, J ¼ 9.0 Hz, 1H, -ArH), 7.89 (d, J ¼ 6.0 Hz, 1H,
-ArH), 7.73–7.68 (m, 2H, -ArH), 7.51 (t, J ¼ 7.5 Hz, 1H, -ArH), 7.42 (t,
J ¼ 7.5 Hz, 1H, -ArH), 7.29 (s, 2H, -CH2-), 7.16 (t, J ¼ 9.0 Hz, 2H, -ArH)
ppm. 13C NMR (75 MHz, DMSO-d6) d: 164.9, 162.5, 158.0
(1JCF ¼ 238.6 Hz), 148.0, 144.3, 135.2 121.0 (3JCF ¼ 7.5 Hz), 116.5,
116.4, 115.2 (2JCF ¼ 21.8 Hz), 114.5, 109.6, 35.1 ppm.
2-((3-Cyano-6-(trifluoromethyl)pyridin-2-yl)thio)-N-(2-fluorophenyl)
acetamide (LBJ-09). The title compound was prepared from 18a
and 21d following the synthesis route of LBJ-þ01. White solid
(1.6 g, 45%). m.p. 208–211 ꢀC. HRMS m/z [M þ H] calculated for
C15H10F4N3OS: 356.0475, found: 356.0473. 1H NMR (300 MHz,
DMSO-d6) d: 10.14 (s, 1H, -NH-), 8.56 (d, J ¼ 9.0 Hz, 1H, -ArH), 7.83
(d, J ¼ 9.0 Hz, 2H, -ArH), 7.30–7.23 (m, 1H, -ArH), 7.16–7.212 (m, 2H,
-ArH), 4.33 (s, 2H, -CH2-) ppm.
2-((3-Cyanopyridin-2-yl)thio)-N-(4-fluorophenyl)acetamide (LBJ-03).
The title compound was prepared from 2-chloro-3-cyanopyridine
and 21b following the synthesis route of LBJ-01. Yellow solid
(1.3 g, 45%). m.p. 198–201 ꢀC. HRMS m/z [M þ H]þ calculated for
C14H11FN3OS: 288.0601, found: 288.0605. 1H NMR (300 MHz,
DMSO-d6) d: 10.41 (s, 1H, -NH-), 8.71–8.69 (m, 1H, -ArH), 8.29–8.26
(m, 1H, -ArH), 7.63–7.58 (m, 2H, -ArH), 7.38–7.33 (m, 1H, -ArH), 7.17
(t, J ¼ 8.9 Hz, 2H, -ArH), 4.26 (s, 2H, -CH2-) ppm.
N-(3-chloro-4-fluorophenyl)-2-((3-cyano-6-(trifluoromethyl)pyridin-
2-yl)thio) acetamide (LBJ-10). The title compound was prepared
from 18a and 21e following the synthesis route of LBJ-01. White
solid (1.9 g, 48%). m.p. 227–229 ꢀC. HRMS m/z [M þ H]þ calculated
for C15H9ClF4N3OS: 390.0085, found: 390.0077. 1H NMR (300 MHz,
DMSO-d6) d: 10.58 (s, 1H, -NH-), 8.56 (d, J ¼ 9.0 Hz, 1H, -ArH),
7.87–7.81 (m, 2H, -ArH), 7.46–7.35 (m, 2H, -ArH), 4.25 (s, 2H, -CH2-)
ppm. 13C NMR (75 MHz, DMSO-d6) d: 163.6, 158.4 (1JCF ¼ 238.5 Hz),
147.5, 145.5, 142.7, 137.5, 135.0, 133.5, 123.3 (3JCF ¼ 8.0 Hz), 116.4,
115.1 (2JCF ¼ 22.0 Hz), 101.5, 54.25 ppm.
2-((4-Cyanopyridin-3-yl)thio)-N-(4-fluorophenyl)acetamide (LBJ-04).
The title compound was prepared from 3-chloro-4-cyanopyridine
and 21b following the synthesis route of LBJ-01. Yellow solid
(1.2 g, 43%). m.p. 206–209 ꢀC. HRMS m/z [M þ H]þ calculated for
C14H11FN3OS: 288.0601, found: 288.0603. 1H NMR (300 MHz,
DMSO-d6) d: 10.37 (s, 1H, -NH-), 8.69–8.67 (m, 1H, -ArH), 8.27–8.24
(m, 1H, -ArH), 7.61–7.56 (m, 2H, -ArH), 7.36–7.31 (m, 1H, -ArH),
7.18–7.12 (m, 2H, -ArH), 4.24 (s, 2H, -CH2-) ppm.
2-((3-Cyanopyridin-4-yl)thio)-N-(4-fluorophenyl)acetamide (LBJ-05).
The title compound was prepared from 4-chloro-3-cyanopyridine
and 21b following the synthesis route of LBJ-þ01. White solid
2-((3-Cyano-6-(trifluoromethyl)pyridin-2-yl)thio)-N-phenylaceta-
mide (LBJ-11). The title compound was prepared from 18a and
(1.3 g, 44%). m.p. 232–234 ꢀC. HRMS m/z [M þ H] calculated for 21c following the synthesis route of LBJ-01. Yellow solid (0.75 g,
C14H11FN3OS: 288.0601, found: 288.0603. 1H NMR (300 MHz, 23%). m.p. 230–233 ꢀC. HRMS m/z [M þ H]þ calculated for