Kislyi et al.
formed is filtered off and washed with MeOH. Yield: 0.18 g
(62%). Red crystals, mp 192-195 °C (EtOH). H NMR (DMSO-
spectrum: 2.59 (s, 3H), 3.48 (s, 3H), 7.42 (d, J ) 2.1 Hz, 1H),
7.69 (d, J ) 2.1 Hz, 1H). Ratio 7c/7d 6:1.
1
d6, δ): 2.55 (s, 3H), 2.94 (d, J ) 5.0 Hz, 3H), 3.47 (s, 3H), 7.00
(d, J ) 2.1 Hz, 1H), 7.21 (d, J ) 2.1 Hz, 1H), 8.83 (br.q, J ) 5.0
Hz, 1H, NH). 13C NMR (DMSO-d6, δ): 23.1, 29.4, 30.4, 96.7,
105.0, 107.3, 149.6, 151.5, 151.7, 157.0, 162.8. EI-MS (70 eV)
(m/z, I, %): 248 [M+, 77], 202 [6], 56 [100]. Anal. Calcd for
C11H12N4O3: C, 53.22; H, 4.87; N, 22.57. Found: C, 53.49; H,
4.71; N, 22.38.
Preparation of 5-Alkylamino-2,3-dimethyl-7-nitroquinazo-
line-4(3H)-ones 6a-j (General Procedure). A solution of 2,3-
dimethyl-5,7-dinitroquinazolinone 5 (0.4 g, 1.52 mmol) and the
corresponding amine (6.06 mmol) (in the case of methylamine and
dimethylamine, a 10-fold excess of 40% aq. solution is used) in
BuOH (5 mL) (in the case of methylamine and dimethylamine,
EtOH is used) is refluxed for 1 h and cooled. The precipitate thus
formed is filtered off in 3 h and washed with MeOH. The resulting
red crystals could be recrystallized from EtOH (6a, c) or MeCN
(6b, d-j).
5-Amino-2,3-dimethyl-7-nitroquinazoline-4(3H)-one(8),7-Amino-
2,3-dimethyl-5-nitroquinazoline-4(3H)-one (8′). To a solution of
the mixture of isomers 7c and 7d (0.34 g, 1.31 mmol) in MeCN
(10 mL) NaI (1.77 g, 11.78 mmol) and FeCl3 (0.32 g, 1.96 mmol)
are added. The mixture is stirred for 30 min and filtered. The filtrate
is evaporated to dryness, and the residue is washed with 10% aq.
Na2S2O3 and then with water. Yield of the mixture of isomers: 0.28
g (92%). Red crystals. Major isomer is 5-amino-2,3-dimethyl-7-
1
nitroquinazoline-4(3H)-one 8. H NMR (DMSO-d6, δ): 2.55 (s,
3H), 3.47 (s, 3H), 7.17 (d, J ) 2.2 Hz, 1H), 7.31 (d, J ) 2.2 Hz,
1
1H), 7.65 (br.s., 2H). Signals of the minor isomer 8′ in H NMR
spectrum (DMSO-d6, δ): 2.56 (s, 3H), 3.40 (s, 3H), 6.55 (br.s,
2H), 6.66 (s, 1H), 6.82 (s, 1H). Ratio 8/8′ 6:1. EI-MS (70 eV) (m/
z, I, %): 234 [M+, 67], 204 [22], 188 [47], 56 [100].
Preparation of 7-Alkylsulfanyl-5-nitroquinazoline-4(3H)-ones
9a-c (General Procedure). A suspension of 5,7-dinitroquinazoli-
none 4 or 5 (1.50 mmol), a corresponding alkanethiol (1.52 mmol),
and K2CO3 (0.31 g, 2.27 mmol) in DMF (7 mL) is stirred for 40
min at rt. The mixture is poured into water (100 mL) and acidified
to pH 3. The precipitate is filtered off and washed with water.
7-Butylsulfanyl-2-methyl-5-nitroquinazoline-4(3H)-one (9a).
5-((4-Methoxyphenyl)amino)-2,3-dimethyl-7-nitroquinazoline-
4(3H)-one (6k). A solution of 2,3-dimethyl-5,7-dinitroquinazolinone
5 (0.26 g, 1.0 mmol) and p-methoxyaniline (0.37 g, 3.0 mmol) in
DMF (5 mL) is stirred at 100 °C for 10 h. The mixture is poured
into water (100 mL) and acidified to pH 3, and the precipitate is
filtered off and purified by flash-chromatography (silica gel,
eluent: heptane-EtOAc from 9:1 to 1:1). Yield: 0.12 g (35%).
1
Yield: 85%, mp 218-220 °C (MeOH). H NMR (DMSO-d6, δ):
0.91 (t, 3H, J ) 7.5 Hz); 1.43 (m, 2H), 1.62 (m, 2H), 2.36 (s, 3H),
3.18 (t, J ) 7.5 Hz, 2H), 7.54 (s, 1H), 7.71 (s, 1H), 12.53 (br.s,
1H). 13C NMR (DMSO-d6, δ): 13.5, 21.4, 21.5, 30.0, 30.4, 107.6,
117.5, 123.8, 146.8, 148.4, 150.2, 157.2, 158.0. EI-MS (70 eV)
(m/z, I, %): 294 [12], 293 [M+, 82], 237 [100]. Anal. Calcd for
C13H15N3O3S: C, 53.23; H, 5.15; N, 14.32; S, 10.93. Found: C,
53.51; H, 5.27; N, 14.12; S, 10.65.
1
Red powder, mp 150-152 °C (MeCN). H NMR (DMSO-d6, δ):
2.60 (s, 3H), 3.52 (s, 3H), 3.80 (s, 3H), 7.05 (d, J ) 8.3 Hz, 2H),
7.27 (d, J ) 2.1 Hz, 1H), 7.31 (d, J ) 8.3 Hz, 2H), 7.36 (d, J )
2.1 Hz, 1H), 10.51 (br.s, 1H). EI-MS (70 eV) (m/z, I, %): 340
[M+, 100], 325 [70], 279 [31], 165 [30]. Anal. Calcd for
C17H16N4O4: C, 59.99; H, 4.74; N, 16.46. Found: C, 60.26; H,
4.81; N, 16.22.
2-Methyl-7-nitro-5-(phenylsulfanyl)quinazoline-4(3H)-one (9d),
2-Methyl-5-nitro-7-(phenylsulfanyl)quinazoline-4(3H)-one (9e).
A suspension of 2-methyl-5,7-dinitroquinazolinone 4 (0.70 g, 2.80
mmol), thiophenol (0.58 g, 4.20 mmol) and K2CO3 (0.58 g, 2.80
mmol) in DMF (10 mL) is stirred for 40 min at rt. The resulting
precipitate is filtered off and washed with water to yield 2-methyl-
7-nitro-5-(phenylsulfanyl)quinazolin-4(3H)-one 9d. Yield: 0.44 g
(50%). Yellow crystals, mp 260-263 °C (DMF). 1H NMR (DMSO-
d6, δ): 2.38 (s, 3H), 7.11 (s, 1H), 7.64 (m, 5H), 7.84 (s, 1H), 12.56
(br.s, 1H). EI-MS (70 eV) (m/z, I, %): 313 [M+, 100], 266 [18],
171 [23]. Anal. Calcd for C15H11N3O3S: C, 57.50; H, 3.54; N,
13.41; S, 10.23. Found: C, 57.92; H, 3.58; N, 13.30; S, 10.33.
The filtrate is poured into water (100 mL) and acidified to pH 3,
and the precipitate is filtered off and washed with water. Yield of
the mixture of isomers 9d and 9e: 0.23 g (26%). Overall ratio 9d/
9e 3:1.
5-Methylamino-2-methyl-7-nitroquinazoline-4(3H)-one (6l). A
solution of 2-methyl-5,7-dinitroquinazolinone 4 (0.38 g, 1.52 mmol)
and 40% aq. methylamine (1.2 mL, 15 mmol) in EtOH (5 mL) is
refluxed for 5 h and cooled. The resulting precipitate is filtered off
and washed with MeOH. Yellowish-brown crystals. Yield: 0.21 g
1
(58%), decomp > 290 °C (EtOH). H NMR (DMSO-d6, δ): 2.31
(s, 3H), 2.92 (d, J ) 5.0 Hz, 3H), 7.01 (d, J ) 2.1 Hz, 1H), 7.23
(d, J ) 2.1 Hz, 1H), 8.79 (br.s, 1H); 12.37 (br.s, 1H). EI-MS (70
eV) (m/z, I, %): 234 [M+, 100], 188 [34], 159 [32], 147 [73]. Anal.
Calcd for C10H10N4O3: C, 51.28; H, 4.30; N, 23.92. Found: C,
51.59; H, 4.39; N, 23.76.
5-Azido-2-methyl-7-nitroquinazoline-4(3H)-one (7a), 7-Azido-
2-methyl-5-nitroquinazoline-4(3H)-one (7b). A suspension of
2-methyl-5,7-dinitroquinazolinone 4 (0.38 g, 1.52 mmol) and NaN3
(0.10 g, 1.54 mmol) in DMF (7 mL) is stirred at 60 °C for 2 h.
The mixture is poured into water (100 mL) and acidified to pH 3.
The precipitate is filtered off and washed with water. Yield of the
mixture of isomers is 0.26 g. Additional amount of the product
(0.05 g) is obtained by extraction of the filtrate with EtOAc and
evaporation of the solvent. Total yield is 0.31 g (83%). The major
isomer is 5-azido-2-methyl-7-nitroquinazoline-4(3H)-one 7a, de-
comp > 170 °C (50% aq. MeCN). 1H NMR (DMSO-d6, δ): 2.37
(s, 3H), 7.83 (d, J ) 2.0 Hz, 1H), 7.98 (d, J ) 2.0 Hz, 1H), 12.58
(br.s., 1H). EI-MS (70 eV) (m/z, I, %): 221 [20], 220 [M+ - 26,
100], 218 [15]. Anal. Calcd for C9H6N6O3: C, 43.91; H, 2.46; N,
34.14. Found: C, 44.24; H, 2.23; N, 33.90. Signals of minor isomer
7b observed in the spectrum: 7.40 (d, J ) 2.0 Hz, 1H), 7.65 (d, J
) 2.0 Hz, 1H). Ratio 7a/7b 6:1.
Reaction of 5,7-Dinitroquinazoline-4(3H)-ones 4 and 5 with
Phenols (Preparation of 10a-f, General Procedure). A suspen-
sion of 5,7-dinitroquinazolinone 4 or 5 (1.52 mmol), a correspond-
ing phenol (1.56 mmol), and K2CO3 (0.32 g, 2.34 mmol) in DMF
(7 mL) is stirred at 80 °C for 4 h. The mixture is poured into water
(100 mL) and acidified to pH 3, and the precipitate is filtered off
and dissolved in benzene (20 mL). The filtrate is extracted with
benzene (3 × 20 mL). The combined benzene solutions are filtered
through silica gel, and the solvent evaporated to dryness.
2,3-Dimethyl-7-nitro-5-phenoxyquinazoline-4(3H)-one (10a),
2,3-Dimethyl-5-nitro-7-phenoxyquinazoline-4(3H)-one (10b). Yield
of the mixture of isomers: 55%. Major isomer is 2,3-dimethyl-5-
1
nitro-7-phenoxyquinazoline-4(3H)-one 10b. H NMR (DMSO-d6,
δ): 2.52 (s, 3H), 3.46 (s, 3H), 6.90 (d, J ) 2.0 Hz, 1H), 7.24 (d,
J ) 8.0 Hz, 2H), 7.32 (t, J ) 8.0 Hz, 1H), 7.52 (t, J ) 8.0 Hz,
2H), 7.64 (d, J ) 2.0 Hz, 1H). Signals of the minor isomer 10a:
2.60 (s, 3H), 3.47 (s, 3H), 7.07 (d, J ) 8.1 Hz, 2H), 7.22 (t, J )
8.1 Hz, 1H), 7.38 (d, J ) 2.0 Hz, 1H), 7.43 (t, J ) 8.1 Hz, 2H),
7.99 (d, J ) 2.0 Hz, 1H). EI-MS (70 eV) (m/z, I, %): 311 [M+,
35], 281 [53], 253 [24], 97 [65], 56 [100]. Ratio 10a/10b 1:5.
Preparation of 1-Alkylamino-3-nitrodibenz[b,f][1,4]oxazepine-
11(10H)-ones 12a-d (General Procedure). A suspension of 1,3-
5-Azido-2,3-dimethyl-7-nitroquinazoline-4(3H)-one (7c), 7-Azi-
do-2,3-dimethyl-5-nitroquinazoline-4(3H)-one (7d). Prepared from
5 as described above for 7a and 7b. Yield of the mixture of
isomers: 85%. EI-MS (70 eV) (m/z, I, %): 260 [M+, 4], 234 [M+
- 26, 44], 232 [48], 186 [72], 56 [100]. Major isomer is 5-azido-
1
2,3-dimethyl-7-nitroquinazoline-4(3H)-one 7c. H NMR (DMSO-
d6, δ): 2.60 (s, 3H), 3.50 (s, 3H), 7.86 (d, J ) 2.1 Hz, 1H), 8.01
(d, J ) 2.1 Hz, 1H). Signals of minor isomer 7d observed in the
2290 J. Org. Chem., Vol. 73, No. 6, 2008