Methyl (3Z)-3-[(Dimethylamino)methylidene]-6-fluoro-4-oxo-3,4-dihydro-2H-chroman-2-carboxy-
late (2). To a solution of methyl 6-fluoro-4-oxo-3,4-dihydro-2H-chroman-2-carboxylate (1) (4.48 g, 20 mmol)
in DMF (10 ml), DMF–DMA (4.76 g, 40 mmol) was added. The reaction mixture was heated with stirring at
150°C for 6 h. At the end of the reaction, the solvent was evaporated, and the residue was crystallized from a
methanol–acetone mixture, 1:1. Yield 4.6 g (77%); mp 156-157°C. 1H NMR spectrum, δ, ppm (J, Hz): 7.61 (1Н,
3
s, =CHNMe2); 7.38 (1H, dd, JН–F = 8.0, 4J = 3.0, Н-5); 7.16 (1Н, td, 3JH–F = 8.0, 4J = 3.0, 3J = 8.0, Н-7); 6.95
3
(1Н, dd, JH–F = 4.0, J = 8.0, Н-8); 6.22 (1Н, s, Н-2); 3.61 (3Н, s, СО2СН3); 3.26 (6Н, s, N(CH3)2). Mass
spectrum, m/z (Irel, %): 280 [М+Н]+ (100). Found, %: С 60.11; Н 4.92; N 4.96. C14H14FNO4. Calculated, %:
С 60.21; Н 5.05; N 5.02.
Methyl 3-Aminomethylidene-6-fluoro-4-oxo-3,4-dihydro-2H-chroman-2-carboxylates (4a-p)
(General Method). To a solution of compound 2 (0.27 g, 1 mmol) in dioxane (5 ml), corresponding amine
3a-p (2.5 mmol) was added. The reaction mixture was boiled with stirring for 3-8 h, and the reaction was
monitored by TLC. At the end of the reaction the reaction mixture was evaporated, and the residue was
chromatographed (compounds 4a-i) or crystallized from acetonitrile (compounds 4j-p).
Methyl
(3Z)-3-{[(2-Aminoethyl)amino]methylidene}-6-fluoro-4-oxo-3,4-dihydro-2H-chroman-
2-carboxylate Hydrochloride (5). A solution of compound 4c (0.39 g, 1 mmol) in methanol (10 ml) and conc
HCl (1 ml) was boiled for 2 h. At the end of the reaction, the solvent was evaporated and the residue was
crystallized from 2-propanol. Yield 0.31 g (93%); mp 115-116°C. 1H NMR spectrum, δ, ppm (J, Hz): 9.81 (1H,
3
4
m, NH); 8.61 (1Н, s, =CHN); 8.41 (3Н, m, NH2·HC1); 7.34 (1H, dd, JН–F = 8.0, J = 3.0, Н-5); 7.12 (Н, td,
4
3
3
3JH–F = 8.0, J = 3.0, J = 8.0, Н-7); 6.91 (Н, dd, JH–F = 4.0, J = 8.0, Н-8); 6.16 (1Н, s, Н-2); 3.62 (2Н, m,
CH2CH2NH2); 3.57 (3Н, s, СО2СН3); 2.99 (2Н, m, CH2CH2NH2). Mass spectrum, m/z (Irel, %): 331 [М+Н]+
100. Found, %: С 50.71; Н 4.73; N 8.41. C14H16ClFN204. Calculated, %: С 50.84; Н 4.88; N 8.47.
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