5308
J. Sa˛czewski et al. / Tetrahedron 61 (2005) 5303–5309
1670, 1625, 1440. Anal. Calcd for C7H9N3O: C, 55.62; H,
6.00; N, 27.80. Found: C, 55.32; H, 5.84; N, 28.00.
THF (15 mL) for 0.5 h. After cooling to room temperature,
pure product 12 that precipitated was collected by filtration
and washed; yield 0.17 g (71%); mp 256–257 8C (THF); 1H
NMR (DMSO-d6) d 2.72 (s, 3H, CH3), 4.02 (s, 4H, CH2),
6.69 (s, 1H, CH), 7.52 (m, 3H, CH), 8.08 (m, 2H, CH); 13C
NMR (DMSO-d6) d 25.3, 42.3, 102.5, 127.1, 129.1, 130.9,
136.3, 152.0, 160.8, 161.0, 169.3; IR cmK1 3064, 1677,
1607, 1579, 1548, 1495. Anal. Calcd for C14H13N3O2: C,
65.87; H, 5.13; N, 16.46. Found: C, 65.42; H, 5.25; N, 15.98.
4.1.7. 8-Metoxy-2,8-dihydro-3H-imidazo[1,2-a]pyrimi-
din-5-one (8). Compound 2 (0.5 g, 4.35 mmol) and ethyl
propiolate (0.42 g, 4,35 mmol) were heated at reflux in
ethanol (6 mL) for 0.5 h. The reaction mixture was
concentrated to a volume of 2 mL under reduced pressure
and diethyl ether (10 mL) was added. Pure compound 8 that
precipitated was filtered off and washed with diethyl ether;
yield 0.59 g (81%); mp 135–137 8C (diethyl ether); 1H
NMR (DMSO-d6) d 3.74 (m, 4H, CH2), 3.86 (s, 3H, CH3),
5.13 (d, 1H, CH, JZ8.2 Hz), 7.71 (d, 1H, CH, JZ8.2 Hz);
13C NMR (DMSO-d6) d 44.5, 50.3, 64.0, 97.0, 142.7, 148.0,
159.8; IR cmK1 1683, 1643, 1624, 1439. Anal. Calcd for
C7H9N3O2: C, 50.29; H, 5.43; N, 25.14. Found: C, 50.63; H,
5.75; N, 24.83.
4.1.12. 1-Benzyl-7-phenyl-2,3-dihydro-1H-imidazo[1,2-
a]pyrimidin-5-one (13). Powdered potassium hydroxide
(0.7 g, 12.5 mmol) was added to a stirred suspension of
compound 4 (0.5 g 2.35 mmol) in acetone (12 mL). After
5 min benzyl bromide (0.31 mL, 2.61 mmol) was added in
one portion. Potassium bromide that precipitated was
filtered off. The filtrate was evaporated under reduced
pressure and the oily residue was subjected to flash
chromatography (AcOEt); yield 0.13 g (46%); mp 167 8C;
1H NMR (DMSO-d6) d 3.59 (t, 2H, CH2, JZ9.5 Hz), 4.01
(t, 2H, CH2, JZ9.5 Hz), 4.66 (s, 2H, CH2), 6.25 (s, 1H, CH),
7.30 (m, 1H, CH), 7.38 (m, 4H, CH), 7.44 (m, 3H, CH), 8.01
(m, 2H, CH); 13C NMR (DMSO-d6) d 39.8, 40.2, 98.4,
126.9, 127.8, 128.2, 128.8, 128.9, 130.4, 136.6, 137.2,
156.0, 161.6, 162.0; IR cmK1 1668, 1575, 1553, 1409, 1485.
Anal. Calcd for C19H17N3O: C, 75.23; H, 5.65; N, 13.85.
Found: C, 75.42; H, 5.16; N, 14.00.
4.1.8. 8-Benzyloxy-2,8-dihydro-3H-imidazo[1,2-a]pyri-
midin-5-one (9). Compound 3 (0.3 g, 1.57 mmol) and
ethyl propiolate (0.17 g, 1.73 mmol) were heated at reflux in
ethanol (4 mL) for 0.5 h. Then, the reaction mixture was
evaporated to dryness and the oily residue was extracted
with diethyl ether. Combined organic layers were dried and
evaporated to dryness. Product 9 was recrystallized from
diethyl ether; yield 0.15 g (40%); mp 102–105 8C; 1H NMR
(CDCl3) d 4.03 (m, 4H, CH2), 5.07 (d, 1H, CH, JZ8.3 Hz),
5.21 (s, 2H, CH2), 6.70 (d, 1H, CH, JZ8.3 Hz), 7.44 (m, 5H,
CH); 13C NMR (CDCl3) d 31.9, 37.3, 65.8, 85.1, 116.2,
116.9, 117.4, 120.5, 129.5, 136.3, 147.0; IR cmK1 3073,
2877, 1679, 1645, 1444. Anal. Calcd for C13H13N3O2: C,
64.19; H, 5.39; N, 17.27. Found: C, 64.08; H, 5.03; N, 17.67.
4.1.13. 5-Oxo-7-phenyl-2,3-dihydro-5H-imidazo[1,2-
a]pyrimidine-1-carboxaldehyde (14). To a cooled solution
(0 8C) of compound 4 (0.23 g, 1.08 mmol) in pyridine
(4 mL) and DMF (1 mL), benzenesulfonyl chloride
(0.14 mL, 1.09 mmol) was added dropwise. After stirring
for 24 h at room temperature, the reaction mixture was
concentrated to a volume of 2 mL under reduced pressure.
Then, water (5 mL) was added and the resulting precipitate
was separated by suction and subjected to flash chromato-
graphy (AcOEt/CHCl3 1:3); yield 0.165 g (73%); mp 181–
184 8C; 1H NMR (DMSO-d6) d 4.04 (m, 4H, CH2), 6.71 (s,
1H, CH), 7.52 (m, 3H, CH), 8.13 (m, 2H, CH), 9.34 (s, 1H,
CH); 13C NMR (DMSO-d6) d 41.4, 103.4, 127.1, 128.9,
130.9, 135.9, 152.4, 159.6, 160.7, 160.9; IR cmK1 1668,
1669, 1613, 1579, 1543, 1593; EIMS m/z (relative intensity)
241 (MC, 60), 212 (MCKCHO, 100), 186 (10). Anal.
Calcd for C13H11N3O2: C, 64.72; H, 4.60; N, 17.42. Found:
C, 65.22; H, 4.55; N, 16.97.
4.1.9. 8-Metoxy-7-methyl-2,8-dihydro-3H-imidazo[1,2-
a]pyrimidin-5-one (10). Compound 2 (0.5 g, 4.35 mmol)
and ethyl 2-butyonate (0.48 g, 4.35 mmol) were refluxed in
ethanol (6 mL) for 0.5 h. The reaction mixture was
evaporated under reduced pressure and the residue was
subjected to flash chromatography (AcOEt/ methanol 5:2);
1
yield 0.47 g (60%); mp 115–119 8C; H NMR (CDCl3) d
2.17 (s, 3H, CH3) 3.95 (m, 4H, CH2), 3.97 (s, 3H, OCH3),
5.07 (s, 1H, CH); IR cmK1 1683, 1644, 1607, 1451; EIMS
m/z (relative intensity) 181 (MC, 53), 151 (MCKOCH3,
100). Anal. Calcd for C8H11N3O2: C, 53.03; H, 6.12; N,
23.19. Found: C, 52.71; H, 6.43; N, 23.63.
4.1.10. 2,3-Dihydro-1H-imidazo[1,2-a]pyrimidin-5-one
(11). Compound 3 (0.3 g, 1.57 mmol) and ethyl propiolate
(0.17 g, 1.73 mmol) were refluxed in ethanol (4 mL) for
10 h. Then, the reaction mixture was evaporated to dryness,
washed with diethyl ether and subjected to flash chromato-
graphy (AcOEt/MeOH 9:1); yield of product 11: 0.08 g
An analogous reaction of 4 with methanesulfonyl chloride
gave the product 14 in 70% yield.
4.2. X-ray structure determination
1
(38%); mp 157–161 8C (acetone); H NMR (DMSO-d6) d
3.58 (t, 2H, CH2, JZ8.8 Hz), 4.00 (t, 2H, CH2, JZ8.8 Hz),
5.54 (d, 1H, CH, JZ6.3 Hz), 7.50 (d, 1H, CH, JZ6.3 Hz),
7.94 (br s, 1H, NH); 13C NMR (DMSO-d6) d 39.5, 42.6,
102.8, 156.1, 159.3, 161.0; IR cmK1 3262, 3115, 2979,
2867, 1674, 1614, 1433, 1285. Anal. Calcd for C6H7N3O: C,
52.55; H, 5.14; N, 30.64. Found: C, 52.61; H, 5.43; N, 30.22.
The intensity data for the crystals have been collected using
a diffractometer equipped with a CCD camera. The crystal
structures have been solved with SHELXS-9721 and refined
with SHELXL-97.22
Crystal data for C10H13N3O (3, CCDC 259437): ortho-
˚
rhombic, space group Pbca, aZ10.5139(4) A, bZ
3
˚
˚
˚
4.1.11. 1-Acetyl-7-phenyl-2,3-dihydro-1H-imidazo[1,2-
a]pyrimidin-5-one (12). Compound 4 (0.2 g 0.93 mmol),
acetic anhydride (2 mL) and Et3N (2.5 mL) were refluxed in
8.0906(3) A, cZ23.4330(7) A, VZ1993.30(12) A , ZZ8,
˚
lZ0.71073 A, TZ130 K, R1Z0.0331, wR2Z0.0830 for
1860 independent reflections with IO2s(I).