2310
N. Zanatta et al.
PAPER
1H NMR (DMSO-d6/TMS): d = 9.68 (s, 1 H, H-4), 8.42 (d, 1 H,
J = 8.1 Hz, H-6), 7.92 (d, 1 H, J = 8.1 Hz, H-9), 7.61 (t, 1 H, J = 8.1
Hz, H-8), 7.50 (t, 1 H, J = 8.1 Hz, H-7), 4.65 (s, 1 H, OH), 3.55 (t,
2 H, J = 5.4 Hz, H-1¢), 2.87 (t, 2 H, J = 5.4 Hz, H-3¢), 1.87 (m, 2 H,
H-2¢).
1H NMR (DMSO-d6/TMS): d = 12.57 (br s, 1 H, NH), 8.73 (s, 1 H,
H-4), 7.85 (d, 1 H, J = 7.1 Hz, H-6), 7.50 (d, 1 H, J = 7.1 Hz, H-9),
7.33–7.19 (m, 2 H, H-7, H-8), 2.00 (s, 3 H, CH3).
13C NMR (DMSO-d6/TMS): d = 162.9 (C-2), 147.1 (C-10a), 140.4
(C-9a), 130.5 (C-4), 128.3 (C-5a), 123.8 (C-8), 120.8 (C-7), 116.8
(C-9), 113.9 (C-3), 109.9 (C-6), 13.2 (CH3).
2
13C NMR (DMSO-d6/TMS): d = 149.5 (q, JC,F = 33.4 Hz, C-2),
147.1 (C-10a), 144.6 (C-9a), 137.8 (C-4), 127.0 (C-8), 126.6 (C-
1
5a), 122.4 (C-7), 120.98 (q, JC,F = 275.6 Hz, CF3), 119.6 (C-9),
4-Methylpyrimido[1,2-a]benzimidazol-2(1H)-one (6c); Typical
Procedure B
116.8 (C-3), 113.4 (C-6), 59.9 (C-1¢), 33.2 (C-3¢), 24.5 (C-2¢).
19F NMR (DMSO-d6/fluorobenzene): d = –63.96 (CF3).
GC/MS (EI, 70 eV): m/z (%) = 295 (M+, 88), 250 (100), 182 (16).
1H NMR (DMSO-d6/TMS): d = 12.70 (br s, 1 H, NH), 8.38 (d, 1 H,
J = 7.9 Hz, H-6), 7.53 (d, 1 H, J = 7.9 Hz, H-9), 7.43 (t, 1 H, J = 7.9
Hz, H-7), 7.29 (t, 1 H, J = 7.9 Hz, H-8), 5.84 (s, 1 H, H-3), 2.31 (s,
3 H, CH3).
Pyrimido[1,2-a]benzimidazol-2(1H)-one (6a); Typical
Procedure A
13C NMR (DMSO-d6/TMS): d = 159.2 (C-2), 148.2 (C-9a, C-10a),
126.7 (C-4, C-5a), 125.4 (C-8), 121.2 (C-7), 115.0 (C-9), 113.5 (C-
6), 98.4 (C-3), 21.6 (CH3).
Et3N (0.2 mL, 1.4 mmol) was added to a solution of 2 (0.3 g, 1.4
mmol) in toluene (10 mL). The mixture was stirred for 15 min at r.t.
After that, the ketone 5a (0.31 g, 1.4 mmol) was added and the mix-
ture was stirred under reflux until the reaction time was complete
(see Table 2). The solvent was evaporated under reduced pressure.
A mixture of CHCl3–H2O (10:30 mL) was added to the residual sol-
id to dissolve the Et3N salt and the product was filtered and dried in
a desiccator under vacuum.
3-Phenylpyrimido[1,2-a]benzimidazol-2(1H)-one (6d);11b Typi-
cal Procedure B
1H NMR (DMSO-d6/TMS): d = 12.97 (br s, 1 H, NH), 8.49 (d, 1 H,
J = 8.0 Hz, H-6), 8.15–8.10 (m, 2 H, H-8, H-9), 7.49–7.52 (m, 6 H,
H-7, C6H5), 6.63 (s, 1 H, H-3).
13C NMR (DMSO-d6/TMS): d = 159.8 (C-2), 149.5 (C-10a), 137.0
(C-9a), 130.2 (C-4), 129.0, 128.6, 128.4, 127.0 (C6H5), 126.2 (C-8),
125.7 (C-5a), 121.8 (C-7), 115.7 (C-9), 111.0 (C-6), 97.1 (C-3).
Pyrimido[1,2-a]benzimidazol-2(1H)-one (6a); Typical
Procedure B
Et3N (0.2 mL, 1.4 mmol) was added to a solution of 3 (0.19 g, 1.4
mmol) in toluene (10 mL). The mixture was stirred for 15 min at r.t.
After that, the ketone 5a (0.31 g, 1.4 mmol) was added and the mix-
ture was stirred under reflux until the reaction time was complete
(see Table 2). The solvent was evaporated under reduced pressure.
A mixture of CHCl3–H2O (10:30 mL) was added to the residue to
dissolve the Et3N and the product was filtered and dried in a desic-
cator under vacuum; mp 254–257 °C (CHCl3–MeOH, dec.) {Lit.10b
mp 336–339 °C (probably, this is the pyrimido[1,2-a]benzimidazol-
4(1H)-one isomer!)}.
1H NMR (DMSO-d6/TMS): d = 12.26 (br s, 1 H, NH), 9.79 (d, 1 H,
J = 7.3 Hz, H-4), 8.42 (d, 1 H, J = 8.1 Hz, H-6), 7.94 (d, 1 H, J = 8.1
Hz, H-9), 7.77 (d, 1 H, J = 7.3 Hz, H-3), 7.63 (t, 1 H, J = 8.1 Hz, H-
8), 7.53 (t, 1 H, J = 8.1 Hz, H-7).
3-(3-Hydroxypropyl)pyrimido[1,2-a]benzimidazol-2(1H)-one
(6e); Typical Procedure C
Mp 269–270 °C (CHCl3–MeOH).
1H NMR (DMSO-d6/TMS): d = 11.70 (br s, 1 H, NH), 7.80 (s, 1 H,
H-4), 7.43–7.39 (m, 2 H, H-6, H-9), 7.09–7.04 (m, 2 H, H-7, H-8),
4.04 (t, 2 H, J = 5.0 Hz, H-1¢), 2.31 (t, 2 H, J = 5.0 Hz, H-3¢), 1.84
(quintet, 2 H, J = 5.0 Hz, H-2¢).
13C NMR (DMSO-d6/TMS): d = 167.2 (C-2), 153.3 (C-4), 147.8
(C-9a, C-10a), 120.9 (C-5a, C-7, C-8, C-9), 113.7 (C-6), 108.6 (C-
3), 66.1 (C-1¢), 20.7 (C-3¢), 18.9 (C-2¢).
GC/MS (EI, 70 eV): m/z (%) = 243 (M+, 18), 213 (28), 111 (100),
83 (28).
13C NMR (DMSO-d6/TMS): d = 161.1 (C-2), 147.2 (C-10a), 143.4
(C-9a), 138.8 (C-4), 127.1 (C-8), 126.8 (C-5a), 123.2 (C-7), 119.1
(C-9), 113.7 (C-6), 102.9 (C-3).
Anal. Calcd for C13H13N3O2 (243.26): C, 64.19; H, 5.39; N, 17.27.
Found: C, 64.19; H, 5.10; N, 17.58.
2a,6a,3,4,5,6-Hexahydropyran[2¢,3¢:6,5]pyrimido[1,2-a]benz-
imidazol-2-one (8e); Procedure A
Mp 260–262 °C (CHCl3–MeOH).
4-Ethoxy-3,4-dihydropyrimido[1,2-a]benzimidazol-2(1H)-one
(8a); Typical Procedure C
1H NMR (DMSO-d6/TMS): d = 11.70 (br s, 1 H, NH), 7.49 (dd, 1H,
J = 3.4 Hz, 2.2 Hz, H-6), 7.43 (dd, 1 H, J = 3.4 Hz, 2.3 Hz, H-9),
7.15–7.13 (m, 2 H, H-8, H-7), 5.92 (d, 1 H, J = 3.6 Hz, H-4), 3.89–
3.87 (m, 1 H, H-1¢), 3.75–3.70 (m, 1 H, H-1¢), 3.23–3.20 (m, 1 H,
H-3), 2.49–2.45 (m, 1 H, H-3¢), 1.83–1.77 (m, 1 H, H-3¢), 1.47–1.43
(m, 2 H, H-2¢).
13C NMR (DMSO-d6/TMS): d = 168.5 (C-2), 147.4 (C-10a), 141.8
(C-9a), 131.8 (C-5a), 122.1 (C-8), 121.2 (C-7), 117.4 (C-9), 109.1
(C-6), 77.6 (C-4), 66.5 (C-1¢), 39.2 (C-3), 21.6 (C-3¢), 21.4 (C-2¢).
Et3N (0.2 mL, 1.4 mmol) was added to a solution of 3 (0.19 g, 1.4
mmol) in MeCN (10 mL). The mixture was stirred for 15 min at r.t.
After that, 5a (0.31 g, 1.4 mmol) was added and the mixture was
stirred at r.t. (under reflux for 5b and 5e) until the reaction time was
complete (see Table 2). The solvent was evaporated under reduced
pressure. A mixture of CHCl3–H2O (10:30 mL) was added to the
residue to dissolve the Et3N and the product was filtered and dried
in a desiccator under vacuum; mp 339–342 °C (CHCl3–MeOH).
1H NMR (DMSO-d6/TMS): d = 11.63 (br s, 1 H, NH), 7.58 (d, 1 H,
J = 8.2 Hz, H-6), 7.43 (d, 1 H, J = 8.2 Hz, H-9), 7.16–7.13 (m, 2 H,
H-7), 6.00–5.8 (m, 1 H, H-4), 3.71–3.67 (m, 1 H, OCH2), 3.41–3.38
(m, 1 H, OCH2), 3.32–3.27 (m, 1 H, H-3), 2.82–2.50 (m, 1 H, H-3),
1.02 (t, 3 H, J = 7.0 Hz, CH3).
CG/MS (EI, 70 eV): m/z (%) = 243 (M+, 34), 213 (18), 111 (100),
83 (18).
Anal Calcd for C13H13N3O2 (243.26): C, 64.19; H, 5.39; N, 17.27.
Found: C, 64.62; H, 5.44; N, 16.91.
13C NMR (DMSO-d6/TMS): d = 167.2 (C-2), 147.3 (C-10a), 141.6
(C-9a), 132.9 (C-5a), 122.1 (C-8), 121.4 (C-7), 117.6 (C-9), 109.4
(C-6), 77.6 (C-4), 64.1 (OCH2), 37.7(C-3), 14.9 (CH3).
1-(1-Ethoxy-4,4,4,-trifluoro-3-oxobuten-1-yl)pyrimido[1,2-
a]benzimidazol-2(1H)-one (10)
K2CO3 (1.38 g, 1.0 mmol) was added to a solution of 6a (0.185 g,
1.0 mmol) in acetone (15 mL). The mixture was stirred for 15 min
at r.t. Ketone 9 (0.212 g, 1.0 mmol) was added and the mixture was
3-Methylpyrimido[1,2-a]benzimidazol-2(1H)-one (6b); Typical
Procedure C
Mp 284–285 °C (CHCl3–MeOH, dec.).
Synthesis 2006, No. 14, 2305–2312 © Thieme Stuttgart · New York