2302
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 11, November, 2007
Savina et al.
Table 2. 1H NMR spectra of compounds 3—8 (DMSOꢀd6)
Comꢀ
pound
δ (J/Hz)
С(3)H2
(s, 2 H)
N(4)H
—
H(5)—H(8)
(m)
Substituent
at the C(9) atom
3
5.14
7.43 (1 H); 7.73 (2 H); 8.39 (1 H)
1.29 (t, 3 H, СH2СH3, J = 7.0); 4.05 (m, 2 H,
СH2СH3); 8.06 (t, 1 H, NH, J = 5.2)
4
5
6
5.23
5.48
5.17
12.70 (br.s)
7.42, 7.57, 7.71, 8.19 (all 1 H each)
7.86, 8.05, 8.17, 8.45 (all 1 H each)
7.23—730, 7.48, 7.76, 8.48
—
—
—
—
5.38 (d, 2 H, СH2, J = 6.4); 8.65 (t, 1 H, NH)
(all m, 5 H + 1 H + 2 H + 1 H)*
7
8
5.26
5.67
—
—
7.52, 7.79, 7.89, 8.21 (all 1 H each) 3.79—3.89 (m, 8 H, (CH2)4O)
7.76, 7.89, 7.96—8.23, 8.39
7.29 (br.s, 2 H, NH2)
(all m, 1 H + 1 H + 3 H + 3 H)*
* Overlap with the signals for the substituent at the C(9) atom.
Furo[3,4ꢀb]quinolineꢀ1,9(3H,4H )ꢀdione (4). Compound 2
(7.53 g, 30 mmol) was added at 40 °C to a stirred solution
of sodium ethoxide prepared from metallic sodium (1.73 g,
75 mmol) and anhydrous EtOH (80 mL). The reaction mixture
was stirred at 40—45 °C for 6 h. On cooling to 20 °C, the
precipitate that formed was filtered off and suspended in water
(100 mL). The stirred suspension was acidified under cooling
with dilute HCl to pH 5. The product was filtered off, washed
with water, and dried to give compound 4 (4.1 g).
9ꢀChlorofuro[3,4ꢀb]quinolinꢀ1(3H )ꢀone (5). Phosphoryl
chloride (6.4 mL) was added dropwise at 5 2 °C for 30 min to
stirred DMF (10 mL). The mixture was stirred at this temperaꢀ
ture for 10 min. Compound 4 (1.23 g, 6 mmol) was added and
the reaction mixture was stirred at 20 °C for 4 h. The precipitate
that formed was filtered off, washed with DMF, and suspended
in water (100 mL). The suspension was stirred for 30 min and
the precipitate was filtered off, washed with water, and dried to
give compound 5 (0.95 g).
9ꢀ(Benzylamino)furo[3,4ꢀb]quinolinꢀ1(3H )ꢀone (6). Benzylꢀ
amine (0.21 g, 2 mmol) was added to a stirred suspension of
compound 5 (0.22 g, 1 mmol) in EtOH (10 mL). The mixture
was refluxed with stirring for 1 h. On cooling, the precipitate
that formed was filtered off, washed with ethanol, and dried to
give compound 6 (0.21 g).
9ꢀMorpholinofuro[3,4ꢀb]quinolinꢀ1(3H )ꢀone (7) and 3ꢀamiꢀ
noꢀ1ꢀ(1ꢀoxoꢀ1,3ꢀdihydrofuro[3,4ꢀb]quinolinꢀ9ꢀyl)pyridinium
chloride (8) were obtained analogously. In the synthesis of comꢀ
pound 8, the reaction mixture was refluxed for 6 h.
3ꢀ(Dimethylaminomethylidene)ꢀ4ꢀmethylfuro[3,4ꢀb]quinoꢀ
lineꢀ1,9(3H,4H )ꢀdione (9). Dimethylformamide dimethyl acetal
(3.0 g, 25 mmol) was added to a stirred suspension of comꢀ
pound 4 (0.3 g, 1.5 mmol) in DMF (6 mL). The mixture was
refluxed with stirring for 3 h. On cooling, the precipitate that
formed was filtered off, washed with DMF and water, and dried
to give compound 9 (0.1 g). 1H NMR (DMSOꢀd6), δ: 3.28 (s,
6 H, NMe2); 3.84 (s, 3 H, Me); 7.19 (s, 1 H, H(1´)); 7.36, 7.74,
8.18 (all m, 1 H + 2 H + 1 H, H(5)—H(8)).
2ꢀ[(5ꢀOxoꢀ2,5ꢀdihydroꢀ3ꢀfuryl)amino]benzoic acid (10).
A. Compound 2 (2.47 g, 10 mmol) was added to a solution of
NaOH (0.44 g, 11 mmol) in ethanol (50 mL). The resulting
suspension was refluxed with stirring for 30 min. On cooling, the
precipitate that formed was filtered off, washed with ethanol,
dried, and dissolved in water (25 mL). The solution was acidiꢀ
fied with conc. HCl to pH 6—7. The precipitate that formed was
filtered off, washed with water, and dried to give compound 10
1
(1.87 g). H NMR (DMSOꢀd6), δ: 4.93 (s, 2 H, C(2´)H2); 5.48
(s, 1 H, H(4´)); 7.14, 7.50, 7.60, 8.00 (all m, 1 H each,
H(3)—H(6)); 10.43 (br.s, 1 H, NH); 13.50 (br.s, 1 H, COOH).
B. A mixture of tetronic acid (2.0 g, 20 mmol) and anthraꢀ
nilic acid (2.74 g, 20 mmol) was refluxed in stirred MeOH
(20 mL) for 6 h. On cooling, the precipitate that formed was
filtered off, washed with methanol, and dried to give comꢀ
pound 10 (2.97 g).
3ꢀ(Dimethylaminomethylidene)furo[3,4ꢀb]quinolineꢀ
1,9(3H,4H )ꢀdione (11). Phosphoryl chloride (14 mL) was added
dropwise at 5 2 °C for 30 min to stirred DMF (45 mL). The
mixture was stirred at this temperature for 10 min. Then comꢀ
pound 10 (2.97 g, 13.6 mmol) was added and the reaction mixꢀ
ture was stirred at 20 °C for 4 h. The precipitate was filtered off,
washed with DMF, and suspended in water (100 mL). The
suspension was stirred for 30 min and the precipitate was filtered
off, washed with water, and dried. Then it was suspended in
ethanol (200 mL) and the stirred suspension was alkalified with
1 M NaOH to pH 7—7.5. On cooling, the precipitate was filꢀ
tered off, washed with ethanol, and dried to give compound 11
(1.8 g) as a mixture of Eꢀ and Zꢀisomers (5 : 1). 1H NMR
(DMSOꢀd6), δ: 3.41, 3.65 (both s, 3 H each, NMe2); 7.25
and 7.35, 7.48 and 7.52, 7.57 and 7.72, 8.15 and 8.03 (all m,
1 H each, H(5)—H(8)); 8.02, 7.69 (s, 1 H, H(1´)); 11.63, 11.28
(br.s, 1 H, NH).
3ꢀ(Benzylaminomethylidene)furo[3,4ꢀb]quinolineꢀ
1,9(3H,4H )ꢀdione (12). A suspension of compound 11 (0.13 g,
0.445 mmol) and benzylamine (0.090 g, 0.89 mmol) in ethanol
(5 mL) was stirred for 4 h. The precipitate was filtered off,
washed with ethanol, dried, and recrystallized from DMF to
give compound 12 (0.09 g). 1H NMR (DMSOꢀd6), δ: 4.68 (d,
2 H, CH2Ph, J = 6.0 Hz); 7.21—7.56, 8.15 (both m, 8 H + 1 H,
Ph, H(5)—H(8)); 8.31 (d, 1 H, H(1´), J = 14.7 Hz); 9.78 (m,
1 H, NHCH2Ph); 11.84 (br.s, 1 H, N(4)H).
3ꢀ(Morpholinomethylidene)furo[3,4ꢀb]quinolineꢀ
1,9(3H,4H )ꢀdione (13) was obtained analogously.
Ethyl 2ꢀ{[(2ꢀdimethylaminomethylidene)ꢀ4ꢀformylꢀ5ꢀoxoꢀ
2,5ꢀdihydroꢀ3ꢀfuryl]amino}benzoate (14). Phosphoryl chloride
(9 mL) was added dropwise at 5 2 °C for 30 min to stirred DMF
(30 mL). The mixture was stirred at this temperature for 10 min
and then compound 2 (2.47 g, 10 mmol) was added. The reacꢀ
Savina
