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Russ.Chem.Bull., Int.Ed., Vol. 58, No. 11, November, 2009
Ponomarev et al.
4 h in Ac2O (8 mL) using a condenser equipped with a calcium
chloride drying tube, then heating was stopped, and the reaction
mixture was kept for ~14 h. Then, the solution was triturated
with a glass rod in a glass flask, the crystalline mass obtained was
diluted with diethyl ether (30 mL), a precipitate was filtered off
and washed with diethyl ether. The yield was 3.04 g (70%), m.p.
115 °C (cf. Ref. 13: m.p. 116.5—117.5 °C).
C, 71.62; H, 3.30; F, 9.80; N, 10.95. C23H13F2N3O. Calculꢀ
ated (%): C, 71.68; H, 3.44; F, 9.86; N, 10.90.
2,3ꢀBis(4ꢀbromophenyl)ꢀ10Hꢀpyridazino[6,1ꢀb]quinazolinꢀ
10ꢀone (5) was obtained similarly to compound 3 by the reaction
of compound 2 with 4,4´ꢀdibromobenzil (0.74 g, 2 mmol).
The yield was 0.70 g (62%), m.p. 193—196 °C. 1H NMR
(DMSOꢀd6), δ: 6.98 (d, 2 H, J = 7.1 Hz); 7.18 (d, 2 H,
J = 7.9 Hz); 7.32—7.49 (m, 4 H); 7.56 (d, 1 H, J = 7.0 Hz); 7.62
(s, 1 H, —CH=); 7.68—7.78 (m, 2 H); 8.44 (d, 1 H, J = 7.3 Hz).
Found (%): C, 54.52; H, 2.50; Br, 31.56; N, 8.34. C23H13Br2N3O.
Calculated (%): C, 54.47; H, 2.58; Br, 31.51; N, 8.29.
9HꢀAcenaphtho[1´,2´:3,4]pyridazino[6,1ꢀb]quinazolinꢀ9ꢀone
(6). 3ꢀAminoꢀ2ꢀmethylquinazolone (2) (0.184 g, 1 mmol) and
acenaphthenequinone (0.182 g, 1 mmol) in PFP (0.3 g) were
heated for 1.5 h at 70 °C. Gradual formation of a precipitate
was observed. The reaction mixture was diluted with ethanol
(10 mL), an orange precipitate was filtered off, washed with
acetone, and dried. The yield was 0.28 g (87%), m.p. >350 °C.
TLC: Rf = 0.4, a fluorescing spot. 1H NMR (CF3COOD), δ:
7.30—8.52 (m, 4 H); 8.69 (t, 1 H, J = 7.8 Hz); 8.82 (d, 1 H,
J = 8.0 Hz); 8.88 (d, 1 H, J = 8.0 Hz); 9.01 (d, 1 H, J = 7.2 Hz);
9.91 (d, 1 H, J = 6.8 Hz); 9.14 (s, 1 H, —CH=); 9.21 (d, 1 H,
J = 8.4 Hz). Found (%): C, 78.52; H, 3.49; N, 13.01. C21H11N3O.
Calculated (%): C, 78.49; H, 3.45; N, 13.08.
Indolo[3´,2´:3,4]pyridazino[6,1ꢀb]quinazolinꢀ7(14H)ꢀone
(7). 3ꢀAminoꢀ2ꢀmethylquinazolone (2) (0.184 g, 1 mmol)
and isatin (0.147 g, 1 mmol) in PFP (0.4 g) were heated for 2 h at
80 °C. Gradual formation of a precipitate was observed. The
reaction mixture was diluted with acetone (10 mL), an orange
precipitate was filtered off, washed with acetone, and dried. The
yield was 0.33 g (100%), m.p. > 350 °C. TLC: Rf = 0.3, a
fluorescing spot. 1H NMR (CF3COOD), δ: 7.54 (t, 1 H,
J = 7.6 Hz); 7.76 (d, 1 H, J = 8.4 Hz); 7.88—8.00 (m, 3 H);
8.26 (t, 1 H, J = 7.6 Hz); 8.36 (d, 1 H, J = 8.0 Hz); 8.74 (d, 1 H,
J = 8.4 Hz); 8.84 (s, 1 H, —CH=). Found (%): C, 71.36;
H, 3.58; N, 19.61. C17H10N4O. Calculated (%): C, 71.32;
H, 3.52; N, 19.57.
15ꢀPhenylꢀ9Hꢀacenaphtho[1´,2´:3,4]pyridazino[6,1ꢀb]ꢀ
quinazolinꢀ9ꢀone (9) was obtained similarly to 6 by the reaction
of 3ꢀaminoꢀ2ꢀbenzylquinazolone (8) (0.251 g, 1 mmol) with
acenaphthenequinone (0.182 g, 1 mmol). The yield was 0.38 g
(96%), m.p. > 350 °C. 1H NMR (CDCl3), δ: 7.11 (d, 1 H,
J = 6.8 Hz); 7.25 (s, 1 H); 7.43—7.53 (m, 2 H); 7.62—7.84 (m,
7 H); 7.93 (d, 1 H, J = 8.0 Hz); 8.03 (d, 1 H, J = 8.0 Hz); 9.01
(d, 1 H, J = 7.2 Hz); 8.50 (d, 1 H, J = 6.8 Hz); 8.54 (d, 1 H,
J = 7.6 Hz). Found (%): C, 81.57; H, 3.75; N, 10.63. C27H15N3O.
Calculated (%): C, 81.60; H, 3.80; N, 10.57.
3ꢀAminoꢀ2ꢀmethylquinazolone (2). 2ꢀMethylbenzoxazinone
(1) (3.22 g, 20 mmol) was dissolved in THF (12 mL) and added
to hydrazine hydrate in excess amount (4 mL, 80 mmol) with
stirring. Formation of white precipitate (acetimidinium salt)
was observed. After addition of 0.5% aq. NaOH (10 mL),
formation of purple emulsion was observed, which was heated
until the color disappeared. The reaction mixture was diluted
with water (20 mL) and a white precipitate formed was filtered
off, washed with water, and dried. The yield was 1.75 g
1
(99%), m.p. 149—150 °C (cf. Ref. 14: m.p. 149.3 °C). H NMR
(CDCl3), δ: 2.70 (s, 3 H, Me); 4.89 (s, 2 H, NH2); 7.43 (t, 1 H,
J = 7.6 Hz); 7.62 (d, 1 H, J = 8.4 Hz); 7.71 (t, 1 H, J = 7.8 Hz);
8.21 (d, 1 H, J = 8.0 Hz).
3ꢀAminoꢀ2ꢀbenzylquinazolone (8) was obtained similarly to
compound 2 by the reaction of 2ꢀbenzylbenzoxazinone (4.75 g,
20 mmol) with hydrazine hydrate. The yield was 4.08 g (81%),
m.p. 160—165 °C (cf. Ref. 15: m.p. 164 °C). 1H NMR (CDCl3),
δ: 4.38 (s, 2 H, —CH2—); 4.78 (s, 2 H, NH2); 7.15—7.50 (m,
6 H); 7.74 (s, 2 H); 8.21 (d, 1 H, J = 7.2 Hz).
3ꢀAminoꢀ6ꢀhydroxyꢀ2ꢀmethylquinazolone (27). 6ꢀAcetoxyꢀ
2ꢀmethylbenzoxazinone (26) (3.03 g, 14 mmol) was dissolved in
THF (16 mL) and added to hydrazine hydrate in excess amount
(4 mL, 80 mmol) with stirring. Sequential formation of a beige
emulsion, exothermic reaction with the formation of solution
with shade of pink, and then formation of white precipitate
(acetimidinium salt) were observed. A 0.5% aq. NaOH (20 mL)
was added to the reaction mixture and the suspension was stirred
for 1 h, then a precipitate was filtered off and washed with water.
The yield was 2.36 g (96%), m.p. 337 °C (with decomp.).
1H NMR (DMSOꢀd6), δ: 2.53 (s, 3 H, Me); 5.76 (s, 2 H, NH2);
7.24 (q, 1 H, J1 = 8.9 Hz, J2 = 2.8 Hz); 7.37 (d, 1 H, J = 2.8 Hz);
7.47 (d, 1 H, J = 8.7 Hz). Found (%): C, 56.50; H, 4.77;
N, 22.05. C9H9N3O2. Calculated (%): C, 56.54; H, 4.74;
N, 21.98.
2,3ꢀDiphenylꢀ10Hꢀpyridazino[6,1ꢀb]quinazolinꢀ10ꢀone (3).
3ꢀAminoꢀ2ꢀmethylquinazolone (2) (0.35 g, 2 mmol) and benzil
(0.42 g, 2 mmol) were heated for 15 h in PFP (0.8 g) at 140 °C.
TLC: Rf = 0.6, a fluorescing spot. The reaction mixture was
cooled and precipitated with methanol (10 mL), a precipitate was
filtered off, dried, and then sublimed at 180 °C and residual presꢀ
sure of 0.01 Torr. The yield was 0.42 g (60%), m.p. 189—190 °C
(cf. Ref. 5: m.p. 189—190 °C). 1H NMR (DMSOꢀd6), δ:
7.25—7.45 (m, 10 H, Ph); 7.60 (t, 1 H, J = 6.7 Hz); 7.82 (d, 1 H,
J = 7.7 Hz); 7.88 (s, 1 H, —CH=); 7.95 (t, 1 H, J = 6.7 Hz); 8.37
(d, 1 H, J = 6.7 Hz). Found (%): C, 79.16; H, 4.22; N, 11.97.
C23H15N3O. Calculated (%): C, 79.07; H, 4.33; N, 12.03.
2,3ꢀBis(4ꢀfluorophenyl)ꢀ10Hꢀpyridazino[6,1ꢀb]quinazolinꢀ
10ꢀone (4) was obtained similarly to compound 3 by the reaction
of compound 2 with 4,4´ꢀdifluorobenzil (0.49 g, 2 mmol).
The yield was 0.50 g (62%), m.p. 186—223 °C (amphoteric
compound). 1H NMR (DMSOꢀd6), δ: 7.12—7.41 (m, 4 H);
7.31—7.36 (m, 2 H); 7.38—7.43 (m, 2 H); 7.59 (t, 1 H,
J = 6.5 Hz); 7.80 (d, 1 H, J = 6.5 Hz); 7.85 (s, 1 H, —CH=);
7.98 (t, 1 H, J = 6.5 Hz); 8.35 (d, 1 H, J = 6.6 Hz). Found (%):
7ꢀBromoꢀ3ꢀhydroxyꢀ9Hꢀacenaphtho[1´,2´:3,4]pyridazinoꢀ
[6,1ꢀb]quinazolinꢀ9ꢀone (28) (ABꢀmonomer) was obtained
similarly to 6 by the reaction of sodium salt of 3ꢀaminoꢀ
6ꢀhydroxyꢀ2ꢀmethylquinazolone (27) (0.640 g, 3 mmol) with
4ꢀbromoacenaphthenequinone (0.783 g, 3 mmol). The yield
was 1.21 g (96%), m.p. > 350 °C. 1H NMR (CF3COOD), δ:
7.30—8.52 (m, 3 H); 8.81 (d, 1 H, J = 8.0 Hz); 8.82 (d, 1 H,
J = 8.4 Hz); 9.01 (d, 1 H, J = 7.6 Hz); 9.91 (s, 1 H); 9.14 (s, 1 H,
—CH=); 9.21 (d, 1 H, J = 8.4 Hz). Found (%): C, 60.64;
H, 2.47; Br, 19.25; N, 10.15. C21H10BrN3O2. Calculated (%):
C, 60.60; H, 2.42; Br, 19.20; N, 10.10.
6,6´ꢀBis(2ꢀmethylbenzoxazinone) (11). Benzidineꢀ3,3´ꢀdiꢀ
carboxylic acid (14.32 g, 50 mmol) was refluxed for 4 h in Ac2O
(50 mL) using a condenser equipped with a calcium chloride