S. M. Sondhi et al. / Bioorg. Med. Chem. 13 (2005) 6158–6166
6163
with cold methanol (2 ml) and then crystallized from
methanol to give pure white solid condensed product
–CH2–), 1.92-1.96 (d, 1H, one H of –CH2–), 2.10–2.36
(m, 2H, C–CH2–C), 3.64–3.87 (m, 2H, –CH2–N),
3.99–4.09 (m, 3H, –CH2–N + >CH–CH3), 4.87 (br s,
1H, –>CH–OH, changes to doublet after D2O exch),
6.25 (br s, 1H, –OH, exch), 6.97–7.05 (d, 2H, Ar), 7.51
(s, 1H, –NH– exch), 7.57 (s, 1H, Ar). FAB-MS m/z
255.76 (MH+, 10%). Anal. Calcd for C11H18N4OS: C,
51.96; H, 7.08; N, 22.04. Found: C, 51.79; H, 6.91; N,
22.13.
2. Yield 0.253 g (73%); mp 200 ꢁC IR (KBr) mmax
:
3451, 2959, 1640, 1539, 1443, 1277, 1187 cmꢁ1 1H
;
NMR (300 MHz, DMSO-d6 + CDCl3) d: 1.38 (s, 6H,
CH3 + CH3), 1.50 (s, 3H, –CH3), 2.00–2.05 (d, 1H,
Jgem = 15 Hz, one H of –CH2–), 2.35–2.40 (d, 1H,
Jgem = 15 Hz, one H of –CH2–), 3.44 (s, 3H, –OCH3),
7.28–7.33 (t, 1H, Ar), 7.37–7.42 (t, 2H, Ar), 7.63 (s,
1H, >C@CH–), 7.87–7.90 (d, 2H, Ar), 8.47 (s, 1H,
–NH); FAB-MS m/z 370.1043 [(MNa)+, 100%]. m/z 316
4.6. Synthesis of 7,7,8a-trimethyl-5-thioxo-1,5,6,7,8,8a-
hexahydroimidazo[1,2-f] pyrimidine-2,3-dicarbonitrile
(5a)
H
N
H
S
S
N
(
,
20%), 315
(
, 7%), 214
S
S
N
N
Ph
N
Ph
N
Diaminomaleonitrile (5) (0.108 g, 1 mmol) was dissolved
in methanol (25 ml) and to it was added 4-isothiocyanat-
o-4-methyl pentane-2-one (1b) (0.2 ml, 1.3 mmol). The
reaction contents were heated under reflux for 12 h
and then solvent was removed under reduced pressure
to give crude product 5a. Crude product 5a was ad-
sorbed over silica gel and subjected to column chroma-
tography over silica gel. Elution with pet. ether/CHCl3
(1:2) gave pure product 5a. Brown solid, 0.115 g
(46%); mp 165 ꢁC; IR (KBr) mmax: 3427, 2981, 2212,
CH
C
S
N
(
, 16%). Anal. Calcd for C17H21N3OS2: C,
CH3
Ph
N
58.78; H, 6.05; N, 12.10. Found: C, 59.01; H, 6.00; N,
12.01.
4.4. Synthesis of 4,4,6-trimethyl-1-(4-phenylthiazol-2-yl)-
3,4-dihydropyrimidine-2(1H)-thione (3)
2-Amino-4-phenyl thiazole (2a) (0.176 g, 1 mmol) was
dissolved in methanol (15 ml) and to it was added
4-isothiocyanato-4-methylpentane-2-one (1b) (0.2 ml,
1.2 mmol). The pH of the reaction contents was adjusted
to ꢀ4 by adding a few drops of 10% H2SO4 in methanol.
The reaction contents were heated under reflux, after 8 h
of refluxing, solid product started separating out and
refluxing was further continued for 3 h. Solvent was re-
moved under reduced pressure and the crude product so
obtained was washed with 10% aq sodium carbonate
solution and then with water and air-dried. Crude con-
densed product 3 was purified by column chromatogra-
phy over silica gel. Elution with CHCl3 removed side
products and further elution with CHCl3/MeOH
(9.5:0.5) gave pure condensed product 3. White solid,
0.236 g (75%); mp 190 ꢁC; IR (KBr) mmax: 3443, 2963,
1630, 1528, 1476, 1283 cmꢁ1 1H NMR (300 MHz
.
DMSO-d6) d: 1.18 (s, 6H, CH3 + CH3), 2.15 (s, 3H,
CH3), 2.63 (s, 2H, –CH2–), 8.39 (s, 1H, NH, exch), other
NH is expected downfield; did not give M+ ion peak in
HR-MS but gave m/z 188.10576 (M+–HSCN, 27.08%),
NC
NC
N
N
187.09779 (
, 1.05%), 173.08265 (
,
NC
NC
N
N
H
NC
N
19.94%), 172.07618 (
, 0.82%); 133.05109
NC
N
H
NC
NH
NC
N
(
,
57.84%), 132.04474 (
, 25.58%),
NC
NC
N
N
H
H
NC
N
NC
N
131.03635 (
, 5.85%), 105.03351 (
,
,
1639, 1542, 1446, 1278 cmꢁ1 1H NMR (300 MHz,
;
NC
N
N
DMSO-d6 + CDCl3) d: 1.47 (d, 6H, CH3 + CH3), 1.70
(s, 3H, –CH3), 4.9 (d, 1H, >C@CH–), 6.86 (bs. 1H,
–NH), 7.29–7.53 (m, 3H, Ar), 7.83 (s, 1H, Ar), 7.89–
7.90 (d, 2H, Ar); FAB-MS m/z 316.94 (MH+, 30%).
Anal. Calcd for C16H17N3S2: C, 60.95; H, 5.39; N,
13.33. Found: C, 61.05; H, 5.24; N, 13.39.
N
3
CH2
7.33%), 79.03018 (
, 4.33%); 56.06246 (H C
H3C
N
100.00%). Anal. Calcd for C11H13N5S: C, 53.44; H,
5.26; N, 28.34. Found: C, 53.41; H, 5.33; N, 28.41.
4.7. Synthesis of 7-methyl-5-thioxo-1,5,6,7,8,8a-hexahy-
droimidazo[1,2-f]pyrimidine-2,3-dicarbonitrile (5b)
4.5. Synthesis of 1-[(3-1H-imidazol-1-yl)propyl]-6-hy-
droxy-4-methyl-tetrahydro pyrimidine-2 (1H)-thione (4)
Diaminomaleonitrile (5) (0.108 g, 1 mmol) was dissolved
in methanol (25 ml) and to it was added 3-isothiocyanat-
obutanal (1c) (0.2 ml, 1.5 mmol). The reaction contents
were allowed to stand at room temperature for 4 days
and then solvent was removed under reduced pressure
to give crude product 5b. Crude product 5b was ad-
sorbed over silica gel and then subjected to column chro-
matography over silica gel. Elution with CHCl3
removed side products and further elution with
CHCl3/EtOAc (4:1) gave pure condensed product 5b.
3-Aminopropyl imidazole (4a) (0.125 g, 1 mmol) was
dissolved in dry methanol (10 ml) and to it was added
3-isothiocyanatobutanal (1c) (0.2 ml, 1.5 mmol). The
reaction contents were allowed to stand at room temper-
ature for 8 days, solvent was removed under reduced
pressure and the crude product was subjected to column
chromatography over silica gel. Elution with CHCl3 re-
moved the side products and further elution with
CHCl3/MeOH (9:1) gave pure condensed product 4.
Brown solid, 0.055 g (25%); mp 220 ꢁC. IR (KBr) mmax
:
3344, 2977, 2212, 1630, 1552, 1460 cmꢁ1 1H NMR
.
White solid, 0.100 g (42%); mp 240 ꢁC; IR (KBr) mmax
:
3421, 2947, 2869, 1627, 1517, 1446, 1279 cmꢁ1 1H
;
(300 MHz DMSO-d6 + CDCl3) d: 1.31–1.33 (d, 3H,
–CH3), 1.58–1.71 (m, 1H, one H of –CH2–), 2.01–2.08
(dd, 1H, one H of –CH2–), 3.19–3.29 (m, 1H, >CH–
NMR (300 MHz, DMSO-d6 + CDCl3) d: 1.20–1.22
(d, 3H, J = 6 Hz, –CH3), 1.25–1.53 (m, 1H, one H of