2013
Novel Pyrimidine-2-thione Derivatives
Synthesis of 3,7-dimethyl-5-phenyl-N-(pyridine-2-yl)-5H-
thiazolo[3,2-a]pyrimidine-6-carboxamide (6). A mixture of
orange crystal (90%). MP 180 ꢀC; IR (KBr) vmax cmÀ1: 3404
(NH), 2961 (C–H), 1706 (C═O amid.), 1580 (C═C). MS: m/z
424 (M+-2, 10%), 334 (62%), 302 (12%), 301 (15%), 199 (9%),
178 (5%), 135 (91%), 77 (100%). Anal. Calcd for C25H22N4OS
(426.53): C, 70.40; H, 5.20; N, 13.14%. Found: C, 70.51; H,
5.34; N, 13.23%.
compound 4 (3.12 g, 10mmol) and chloroacetone (0.925g,
10mmol) in DMF in the presence of anhydrous potassium
carbonate was heated under reflux for 6–7 h (TLC), then the
reaction mixture was left to cool. The solid product formed after
pouring in to ice/water was filtered off and crystallized from
ethanol to give the pure product 6 as dark brown powder (70%);
MP 140ꢀC; IR (KBr) vmax cmÀ1: 3382 (NH), 2921 (C–H), 1660
(C═O), 1597 (C═C). MS: m/z 362 (M+, 15%), 269 (14%), 240
(15%), 220 (12%), 156 (35%), 128 (17%), 78 (100%). Anal.
Calcd for C20H18N4OS (362.45): C, 66.28; H, 5.01; N, 15.46%.
Found: C, 66.35; H, 5.08; N, 15.57%.
Synthesis of 2-(3-bromopropylthio)-4-methyl-6-phenyl-N-
(pyridine-2-yl)-1,6-dihydro-pyrimidine-5-carboxamide (13).
A
mixture of compound 4 (3.12 g, 10 mmol) and 1,3-dibromopropane
(2.02 g, 10 mmol) in DMF (25 mL) was heated under reflux for
1–2 h (TLC), then the reaction mixture was left to cool.
The solid product formed after pouring in to ice/water was
filtered off and crystallized from ethanol to give the pure
product 13 as buff crystal (80%); MP 160 ꢀC; IR (KBr) vmax
cmÀ1: 3367, 3224 (NH), 1710 (C═O amid.), 692 (C–Br).
MS: m/z 445 (M+, 10%), 364 (5%), 350 (6%), 335 (15%), 323
(5%), 322 (7%), 290 (17%), 213 (6%), 146 (6%), 121 (16%),
93 (14%), 78 (70%). Anal. Calcd for C20H21BrN4OS (445.38):
C, 53.94; H, 4.75; N, 12.58%. Found: C, 54.02; H, 4.81; N,
12.65%.
Synthesis of 7-methyl-3-amino-5-phenyl-N-(pyridine-2-yl)-
5H-thiazolo[3,2-a]pyrimidine-6-carboxamide (7).
A mixture
of compound 4 (3.12g, 10mmol) and chloroacetonitrile (0.755g,
10mmol) in DMF (10 mL) containing anhydrous potassium
carbonate was heated under reflux for 8–9 h (TLC), then the
reaction mixture was left to cool. The solid product formed
after pouring in to ice/water was filtered off and crystallized
from ethanol to give the pure product 7 as reddish brown
crystal (73%); MP 170 ꢀC; IR (KBr) vmax cmÀ1: 3386 (NH2, NH),
2969 (C–H), 1657 (C═O), 1580 (C═C). MS: m/z 360 (M+-3,
15%), 332 (5%), 293 (15%), 241 (5%), 128 (22%), 121
(15%), 78 (45%), 67 (100%). Anal. Calcd for C19H17N5OS
(363.44): C, 62.79; H, 4.71; N, 19.27%. Found: C, 62.86; H,
4.77; N, 19.36%.
Synthesis of 7-methyl-3,5-diphenyl-N-(pyridine-2-yl)-5H-
thiazolo[3,2-a]pyrimidine-6-carboxamide (8). A mixture of
compound 4 (3.12 g, 10 mmol) and phenacylbromide (1.99 g,
10 mmol) in DMF (10 mL) in the presence of anhydrous
potassium carbonate was heated under reflux for 5–6 h (TLC),
then the reaction mixture was left to cool. The solid product
formed after pouring in to ice/water was filtered off and
crystallized from ethanol/DMF to give the pure product 8 as
violet crystal (75%). MP 120 ꢀC; IR (KBr) vmax cmÀ1: 3384
(NH), 1674 (C═O), 1594 (C═C). MS: m/z 424 (M+, 10%), 348
(5%), 121 (6%), 105 (50%), 78 (17%), 77 (100%). Anal. Calcd
for C25H20N4OS (424.52): C, 70.73; H, 4.75; N, 13.20%.
Found: C, 70.68; H, 4.71; N, 13.16%.
Synthesis of 6-amino-7-(benzo[d]thiazol-2-yl)-2-methyl-8-oxo-
4-phenyl-N-(pyridine-2-yl)-6,7,8,9-tetrahydro-4H-pyrimido[2,1-b]
[1,3]thiazepine-3-carboxamide (10). A mixture of compound
4 (3.12 g, 10 mmol) and 2-(benzo[d]thiazol-2-yl)-4-chloro-3-
oxobutannitrile (9) (2.495 g, 10 mmol) in DMF (10 mL) in the
presence of anhydrous potassium carbonate was heated under
reflux for 10–12 h (TLC), then the reaction mixture was left to
cool. The solid product formed after pouring in to ice/water was
filtered off and crystallized from ethanol/DMF to give the pure
product 10 as dark brown crystal (85%). MP 230 ꢀC; IR (KBr)
vmax cmÀ1: 3400, 3300 (NH), 2971 (C–H), 1700, 1680 (C═O),
1580 (C═C). MS: m/z 533 (M+-5, 25%), 206 (25%), 174 (75%),
134 (30%), 119 (40%), 77 (25%), 62 (100%). Anal. Calcd for
C22H18N6O2S2 (462.55): C, 57.13; H, 3.92; N, 18.17%. Found:
C, 57.21; H, 3.99; N, 18.29%.
Synthesis of 8-methyl-6-phenyl-N-(pyridine-2-yl)-2,3,4,6-
tetrahydro-pyrimido[2,1-b][1,3] thiazine-7-carboxamide (14).
A
solution of compound 13 (4.45 g, 10mmol) in DMF (20 mL) in
the presence of anhydrous potassium carbonate was heated under
reflux for 5–6 h (TLC), then the reaction mixture was left to cool.
The solid product formed after pouring in to ice/water was filtered
off and crystallized from ethanol/DMF to give the pure product
14 as reddish brown crystal (60%); MP 100ꢀC; IR (KBr) vmax
cmÀ1: 3367 (NH), 1710 (C═O amid.). MS: m/z 364 (M+, 17%),
350 (6%), 335 (15%), 323 (5%), 322 (7%), 290 (17%), 213(6%),
146(6%), 121(16%), 93(14%), 78(70%). Anal. Calcd for
C20H20N4OS (364.46): C, 65.91; H, 5.53; N, 15.37%. Found: C,
65.97; H, 5.61; N, 15.47%.
Synthesis of 4-methyl-2-(methylthio)-6-phenyl-N-(pyridine-
2-yl)-1,6-dihydropyrimidine 5-carboxamide (15). A mixture of
compound 4 (3.12 g, 10 mmol) and methyl iodide (1.46 g, 10 mmol)
in DMF (15 mL) in the presence of anhydrous potassium carbonate
was heated under reflux for 3–5 h (TLC), then the reaction mixture
was left to cool. The solid product formed after pouring in to ice/
water was filtered off and crystallized from ethanol to give the pure
product 15 as yellow sheets (82%). MP 80–90 ꢀC IR (KBr) vmax
cmÀ1: 3384, 3230 (NH), 2990 (C–H aliph.) 1701 (C═O amidic),
1594 (C═C). 1H NMR (CHCl3)(d, ppm): 2.55 (s, 3H, CH3–S),
2.92 (s, 3H, CH3), 5.3 (s, 1H, CH-pyrimidine ring), 7.23–8.07
(m, 9H, Ar–H), and 9.15, 9.6 (s, 2H, 2NH). Anal. Calcd for
C18H18N4OS (338.43): C, 63.88; H, 5.36; N, 16.56%. Found: C,
63.96; H, 5.41; N, 16.67%.
Synthesis of 3-formyl-6-methyl-4-phenyl-N-(pyridine-2-yl)-
2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxamide (16). To
a solution of the appropriate compound 4 (3.12 g, 10mmol) in
DMF (20mL) was added POCl3 (10mmol) under stirring at 0 ꢀC.
The reaction mixture was heated at 85–90ꢀC for 1–2 h, allowed to
cool to room temperature, and poured in 30 mL of ice-cooled
water. The precipitate was separated by filtration and
recrystallized from ethanol to give pure product 16 as light
yellow sheets (57%). MP 166–168 ꢀC. IR (KBr) vmax cmÀ1: 3350,
3230 (NH), 1710(C═O ald.), 1685 (C═O amid.), 1380 (C═S).
MS: m/z 323 (M+-CHO, 18%), 295 (7%), 276 (26%), 248
(10.5%), 223 (7%), 201 (32%), 146 (15%), 121 (28%), 105
(23%), 94 (28%), 78(100%). Anal. Calcd for C18H16N4O2S
(352.41): C, 61.35; H, 4.58; N, 15.90%. Found: C, 61.27; H,
4.53; N, 15.82%.
Synthesis of 2-methyl-4-phenyl-N-(pyridine-2-yl)-6,11-dihydro-
4H-benzo[e]pyrimido [2,1-b][1,3]thiazepine-3-carboxamide (12).
A
mixture of compound 4 (3.12 g, 10 mmol) and o-dibromoxylene
(11) (2.64 g, 10mmol) in DMF (15 mL) was heated under reflux
for 1–2 h (TLC), then the reaction mixture was left to cool. The
solid product formed after pouring in to ice/water was filtered off
and crystallized from ethanol to give the pure product 12 as
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet