Yu et al.
General procedure for the preparation of target
compounds 4a–d
(tC=O), 1271 (tC–N), 1259 (tC–N). ESI-MS: m ⁄ z 464.2 [M+H], 486.2
[M+Na]. C25H22ClN3O2S (463.11).
cCompounds 3a–d (5 mmol) and appropriate N-phenylacetamide
halides (5.5 mmol) were suspended in anhydrous DMF (25 mL) in the
presence of anhydrous potassium carbonate (0.759 g, 5.5 mmol) at
room temperature. The mixtures were irradiated at room tempera-
ture for 12 h. The reaction mixture was poured into cold H2O
(200 mL); the resulting precipitate was collected by filtration under
reduced pressure and washed sequentially with H2O, EtOH, and Et2O
and then dried to give the corresponding crude product, which was
purified by crystallization to give the pure target compounds 4a–d.
2-[(4-bromophenylamino)carbonylmethylthio]-6-
(1-naphthylmethyl)-5-ethylpyrimidin-4(3H)-one
(4b2)
Recrystallized from EtOH-DMF as a white crystal, Yield: 28.7%, mp:
224–226 ꢀC (dec). 1H NMR (DMSO-d6, ppm) d: 12.93 (s, 1H, NH),
10.17 (s, 1H, NH), 8.11–7.08 (m, 11H), 4.28 (s, 2H, S-CH2), 3.91 (s,
2H, CH2), 2.38 (q, J = 7.2 Hz, CH2CH3, 2H), 0.83 (t, J = 7.2 Hz,
CH2CH3, 3H). IR (KBr, ⁄ cm): 3253 (tNH), 3043 (tNH), 1652 (tC=O),
1269 (tC–N), 1244 (tC–N). ESI-MS: m ⁄ z 408.1 [M+H], 530.1 [M+Na].
C25H22BrN3O2S (507.06).
2-[(4-chlorophenylamino)carbonylmethylthio]-6-
(1-naphthylmethyl)-5-methylpyrimidin-4(3H)-one
(4a1)
Recrystallized from EtOH-DMF as a white crystal, Yield: 23.6%, mp:
236–238 ꢀC (dec). 1H NMR (DMSO-d6, ppm) d: 12.74 (s, 1H, NH),
10.18 (s, 1H, NH), 8.10–7.10 (m, 11H), 4.28 (s, 2H, S-CH2), 3.92 (s,
2H, CH2), 1.87 (s, CH3, 3H). IR (KBr, ⁄ cm): 3267 (tNH), 3117 (tNH),
1663 (tC=O), 1268 (tC–N), 1244 (tC–N). ESI-MS: m ⁄ z 450.5 [M+H],
472.4 [M+Na]. C24H20ClN3O2S (449.1).
2-[(4-methoxyphenylamino)carbonylmethylthio]-
6-(1-naphthylmethyl)-5-ethylpyrimidin-4(3H)-one
(4b3)
Recrystallized from EtOH-DMF as a white crystal, Yield: 22.9%, mp:
237–239 ꢀC (dec). 1H NMR (DMSO-d6, ppm) d: 12.95 (s, 1H, NH),
10.09 (s, 1H, NH), 8.14–7.06 (m, 11H), 4.21 (s, 2H, S-CH2), 3.94 (s,
2H, CH2), 3.76 (s, OCH3, 3H), 2.39 (q, J = 7.2 Hz, CH2CH3, 2H), 0.85
(t, J = 7.2 Hz, CH2CH3, 3H). IR (KBr, ⁄ cm): 3255 (tNH), 3130 (tNH),
1650 (tC=O), 1291 (tC–N), 1251 (tC–N).ESI-MS: m ⁄ z 460.2 [M+H],
482.2 [M+Na]. C26H25N3O3S (459.16).
2-[(4-bromophenylamino)carbonylmethylthio]-6-
(1-naphthylmethyl)-5-methylpyrimidin-4(3H)-one
(4a2)
Recrystallized from EtOH-DMF as a white crystal, Yield: 23.9%, mp:
240–242 ꢀC (dec). 1H NMR (DMSO-d6, ppm) d: 12.82 (s, 1H, NH),
10.19 (s, 1H, NH), 8.11–7.10 (m, 11H), 4.26 (s, 2H, S-CH2), 3.91 (s,
2H, CH2), 1.87 (s, CH3, 3H). IR (KBr, ⁄ cm): 3259 (tNH), 3045 (tNH),
1651 (tC=O), 1267 (tC–N), 1244 (tC–N). ESI-MS: m ⁄ z 494.1 [M+H],
516.1 [M+Na]. C24H20BrN3O2S (493.05).
2-[(4-chlorophenylamino)carbonylmethylthio]-6-
(2,6-difluorobenzyl)-5-methylpyrimidin-4(3H)-
one (4c1)
Recrystallized from EtOH-DMF as a white crystal, Yield: 27.1%, mp:
1
248–250 ꢀC (dec). H NMR (DMSO-d6, ppm) d: 12.86 (s, 1H, NH),
10.15 (s, 1H, NH), 7.54 (d, J = 9Hz, 2H), 7.37 (d, J = 9Hz, 2H), 7.15–
6.85 (m, 3H), 3.85 (s, 2H, S-CH2), 3.80 (s, 2H, CH2), 2.00 (s, CH3, 3H).
IR (KBr, ⁄ cm): 3262 (tNH), 3044 (tNH), 1658 (tC=O), 1267 (tC–N), 1247
(tC–N). ESI-MS: m ⁄ z 436.4 [M+H]. C20H16ClF2N3O2S (435.06).
2-[(4-methoxyphenylamino)carbonylmethylthio]-
6-(1-naphthylmethyl)-5-methylpyrimidin-4(3H)-
one (4a3)
Recrystallized from EtOH-DMF as a white crystal, Yield: 24.2%, mp:
239–241 ꢀC (dec). 1H NMR (DMSO-d6, ppm) d: 12.78 (s, 1H, NH),
9.93 (s, 1H, NH), 8.16 (d, J = 8.4Hz, 1H), 7.91 (d, J = 7.8Hz, 1H),
7.75 (d, J = 8.4Hz, 1H), 7.54–7.15 (m, 6H), 6.80 (d, J = 8.4Hz, 2H),
4.30 (s, 2H, S-CH2), 3.90 (s, 2H, CH2), 3.70 (s, OCH3, 3H), 1.89 (s,
CH3, 3H).IR (KBr, ⁄ cm): 3290 (tNH), 3042 (tNH), 1653 (tC=O), 1299
(tC–N), 1246 (tC–N). ESI-MS: m ⁄ z 446.2 [M+H], 468.2 [M+Na].
C25H23N3O3S (445.15).
2-[(4-bromophenylamino)carbonylmethylthio]-6-
(2,6-difluorobenzyl)-5-methylpyrimidin-4(3H)-
one (4c2)
Recrystallized from EtOH-DMF as a white crystal, Yield: 26.6%, mp:
251–253 ꢀC (dec). 1H NMR (DMSO-d6, ppm) d: 12.72 (s, 1H, NH),
10.10 (s, 1H, NH), 7.50–6.87 (m, 7H), 3.85 (s, 2H, S-CH2), 3.82 (s,
2H, CH2), 2.00 (s, CH3, 3H). IR (KBr, ⁄ cm): 3261 (tNH), 3041(tNH),
16594(tC=O), 1267 (tC–N), 1247 (tC–N). ESI-MS: m ⁄ z 480.2 [M+H],
502.2 [M+Na]. C20H16BrF2N3O2S (479.01).
2-[(4-chlorophenylamino)carbonylmethylthio]-6-
(1-naphthylmethyl)-5-ethylpyrimidin-4(3H)-one
(4b1)
Recrystallized from EtOH-DMF as a white crystal, Yield: 25.7%, mp:
mp: 217–219 ꢀC (dec). 1H NMR (DMSO-d6, ppm) d: 12.78 (s, 1H,
NH), 10.17 (s, 1H, NH), 8.12 (d, J = 7.8Hz, 1H), 7.88 (d, J = 7.2Hz,
1H), 7.71(d, J = 7.8Hz, 1H), 7.53–7.09 (m, 8H), 4.29 (s, 2H, S-CH2),
3.92 (s, 2H, CH2), 2.37 (q, J = 7.2 Hz, CH2CH3, 2H), 0.84 (t,
J = 7.2 Hz, CH2CH3, 3H). IR (KBr, ⁄ cm): 3271 (tNH), 3045 (tNH), 1659
2-[(4-methoxyphenylamino)carbonylmethylthio]-
6-(2,6-difluorobenzyl)-5-methylpyrimidin-4(3H)-
one (4c3)
Recrystallized from EtOH-DMF as a white crystal, Yield: 23.5%, mp:
233–235 ꢀC (dec). 1H NMR (DMSO-d6, ppm) d:12.74 (s, 1H, NH),
9.83 (s, 1H, NH), 7.42–6.87 (m, 7H), 3.87 (s, 2H, S-CH2), 3.77 (s, 2H,
CH2), 3.60 (s, OCH3, 3H), 2.00 (s, CH3, 3H). IR (KBr, ⁄ cm): 3257
598
Chem Biol Drug Des 2011; 78: 596–602