All chemical were purchased from the Merck or Aldrich chemical companies and employed without further purification. The reaction progression and purity of the synthesized compounds were checked by TLC (silica gel 60 F-254 plates). The FT-IR spectra were taken on a Perkin Elmer Spectrum Version 10.02.00 employing KBr pellets. The 1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded on a Bruker spectrometer (δ in ppm) by DMSO‐d6 as a solvent with chemical shifts measured relative to TMS as the internal standard. The mass spectra were taken on the Agilent Mass Spectrometer (HP), Model: 5973 Network Mass Selective Detector, Ion source: Electron Impact (EI) 70 eV, Ion source temperature: 230 ºC, with Quadrupole Analyzer. Melting points were measured with a BUCHI 510 melting point apparatus. Elemental analysis was carried out using a MIRA II analyzer. A MIRA III analyzer took the FESEM images. The X-ray diffraction (XRD) measurements were performed with an XRD Philips PW1730. Thermogravimetric-differential thermal analysis (TGA-DTA) was accomplished using an SDT-Q600 device.
Spectral data
2,7-Diamino-4-(3-hydroxyphenyl)-1,8-naphthyridine-3-carbonitrile (4a) Cream solid, M.p. > 350°C, IR (KBr, cm–1): ν = 3513, 3410, 3324, 3197, 2213, 1644 and 1619. 1H NMR (400 MHz, DMSO-d6) δ = 9.80 (s, 1H), 7.36 (t, J = 7.8 Hz, 1H), 7.26 (d, J = 8.9 Hz, 1H), 6.99 (s, 2H), 6.93 (dd, J = 8.1, 2.4 Hz, 1H), 6.80 (s, 2H), 6.78 (s, 1H), 6.75 (d, J = 2.1 Hz, 1H), 6.44 (d, J = 8.9 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ = 162.3, 158.9, 158.5, 157.2, 155.0, 135.8, 135.6, 129.7, 119.5, 116.8, 116.0, 115.7, 109.3, 108.2, 87.3. ESI-mass: m/z = 277.
2,7-Diamino-4-phenyl-1,8-naphthyridine-3-carbonitrile (4b) Yellow pall solid, M.p. > 350°C, IR (KBr, cm–1): ν = 3431, 3320, 3148, 2205, 1607 and 1561. 1H NMR (400 MHz, DMSO-d6) δ = 7.63–7.51 (m, 3H), 7.42 (dd, J = 7.3, 2.3 Hz, 2H), 7.21 (d, J = 8.9 Hz, 1H), 7.01 (s, 2H), 6.84 (s, 2H), 6.44 (d, J = 8.9 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ = 162.3, 158.9, 158.6, 155.0, 135.5, 134.7, 129.1, 129.0, 128.5, 116.8, 109.4, 108.2, 87.5. ESI-mass: m/z = 261.
2,7-Diamino-4-(p-tolyl)-1,8-naphthyridine-3-carbonitrile (4c) Yellow solid, M.p. 331 − 33°C, IR (KBr, cm–1): ν = 3495, 3419, 3389, 3287, 3166, 2207, 1639, 1604 and 1499. 1H NMR (400 MHz, DMSO-d6) δ = 7.38 (d, J = 7.8 Hz, 2H), 7.31 (d, J = 7.9 Hz, 2H), 7.24 (d, J = 9.0 Hz, 1H), 6.99 (s, 2H), 6.81 (s, 2H), 6.44 (d, J = 8.9 Hz, 1H), 2.42 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ = 162.2, 158.9, 158.6, 155.1, 138.7, 135.6, 131.7, 129.1, 129.0, 116.9, 109.3, 108.3, 87.5, 20.8. ESI-mass: m/z = 275.
2,7-Diamino-4-(4-isopropylphenyl)-1,8-naphthyridine-3-carbonitrile (4d) Yellow solid, M.p. > 350°C, IR (KBr, cm–1): ν = 3492, 3429, 3385, 3281, 317, 2958, 2206, 1636, 1603, and 1574. 1H NMR (250 MHz, DMSO-d6) δ = 7.42 (d, J = 7.6 Hz, 2H), 7.34 (s, 2H), 7.22 (d, J = 9.0 Hz, 1H), 6.95 (s, 2H), 6.77 (s, 2H), 6.42 (d, J = 9.2 Hz, 1H), 3.05–2.90 (m, 1H), 1.26 (d, J = 6.2 Hz, 6H). 13C NMR (62.5 MHz, DMSO-d6) δ = 162.76, 159.44, 159.08, 155.47, 149.83, 136.10, 132.51, 129.59, 126.97, 117.48, 109.84, 108.81, 87.95, 33.68, 24.16. ESI-mass: m/z = 303.
2,7-Diamino-4-(4-methoxyphenyl)-1,8-naphthyridine-3-carbonitrile (4e) Yellow pall solid, M.p. 331–333°C decompose, IR (KBr, cm–1): ν = 3500, 3426, 3387, 3273, 3162, 2207, 1605 and 1501. 1H NMR (400 MHz, DMSO-d6) δ = 7.37 (d, J = 8.7 Hz, 2H), 7.28 (d, J = 8.9 Hz, 1H), 7.16–7.10 (m, 2H), 6.99 (s, 2H), 6.80 (s, 2H), 6.44 (d, J = 8.9 Hz, 1H), 3.86 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ = 162.2, 159.8, 158.9, 158.6, 154.8, 135.6, 130.6, 126.6, 117.1, 113.9, 109.2, 108.4, 87.6, 55.2, 40.0. ESI-mass: m/z = 291.
2,7-Diamino-4-(3,4-dimethoxyphenyl)-1,8-naphthyridine-3-carbonitrile (4f) Yellow solid, M.p. 303°C, IR (KBr, cm–1): ν = 3499, 3413, 3387, 3278, 3185, 2829, 2207, 1605, and 1565. 1H NMR (400 MHz, DMSO-d6) δ = 7.35 (d, J = 8.9 Hz, 1H), 7.14 (d, J = 8.3 Hz, 1H), 7.03 (d, J = 2.0 Hz, 1H), 7.01–6.92 (m, 3H), 6.79 (s, 2H), 6.45 (d, J = 8.9 Hz, 1H), 3.85 (s, 3H), 3.78 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ = 162.24, 158.95, 158.62, 154.98, 149.37, 148.43, 135.85, 126.83, 121.76, 117.13, 112.84, 111.54, 109.27, 108.48, 87.70, 55.64, 55.51. ESI-mass: m/z = 321.
2,7-Diamino-4-(4-bromophenyl)-1,8-naphthyridine-3-carbonitrile (4g) Yellow solid, M.p. > 350°C, IR (KBr, cm–1): ν = 3437, 3342, 3203, 2208, 1668, 1634 and 1613. 1H NMR (400 MHz, DMSO-d6) δ = 7.78 (d, J = 8.2 Hz, 2H), 7.40 (d, J = 8.2 Hz, 2H), 7.20 (d, J = 8.9 Hz, 1H), 7.04 (s, 2H), 6.88 (s, 2H), 6.45 (d, J = 9.0 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ = 162.3, 158.8, 158.6, 153.7, 135.4, 133.9, 131.6, 131.2, 122.7, 116.7, 109.6, 108.1, 87.3. ESI-mass: m/z = 339.
2,7-Diamino-4-(4-chlorophenyl)-1,8-naphthyridine-3-carbonitrile (4h) Yellow solid, M.p. °C 338 decompose, IR (KBr, cm–1): ν = 3436, 3341, 3239, 3202, 2209, 1642, 1612 and 1515. 1H NMR (400 MHz, DMSO-d6) δ = 7.65 (d, J = 8.5 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.9 Hz, 1H), 7.04 (s, 2H), 6.88 (s, 2H), 6.45 (d, J = 9.0 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ = 162.3, 158.8, 158.6, 153.7, 135.4, 134.0, 133.5, 131.0, 128.7, 116.7, 109.6, 108.1, 87.4. ESI-mass: m/z = 295.
2,7-Diamino-4-(2,4-dichlorophenyl)-1,8-naphthyridine-3-carbonitrile (4i) Yellow solid, M.p. > 350°C, IR (KBr, cm–1): ν = 3441, 3350, 3182, 2214, 1639, 1610 and 1570. 1H NMR (400 MHz, DMSO-d6) δ = 7.92 (d, J = 2.1 Hz, 1H), 7.65 (dd, J = 8.2, 2.1 Hz, 1H), 7.52 (d, J = 8.2 Hz, 1H), 7.16–6.91 (m, 5H), 6.45 (d, J = 8.9 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ = 162.5, 158.7, 158.6, 151.0, 134.9, 134.8, 132.9, 132.7, 132.2, 129.3, 127.9, 116.1, 109.9, 108.1, 87.7. ESI-mass: m/z = 329.
7-Amino-2-hydroxy-4-(3-nitrophenyl)-1,8-naphthyridine-3-carbonitrile (4j) Ceram solid, M.p. > 350°C, IR (KBr, cm–1): ν = 3397, 3174, 3086, 2938, 2227, 1615, 1536 and 1375. 1H NMR (400 MHz, DMSO-d6) δ = 12.37 (s, 1H), 8.43 (d, J = 8.6 Hz, 1H), 8.34 (s, 1H), 7.96 (d, J = 8.1 Hz, 1H), 7.90 (t, J = 7.9 Hz, 1H), 7.48 (s, 2H), 7.15 (d, J = 9.0 Hz, 1H), 6.38 (d, J = 9.0 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ = 162.1, 160.3, 156.2, 152.1, 147.8, 136.4, 135.5, 135.2, 130.5, 124.4, 123.5, 116.2, 107.5, 104.4, 97.8. ESI-mass: m/z = 307.
7-Amino-2-hydroxy-4-(3-hydroxyphenyl)-1,8-naphthyridine-3-carbonitrile (4k) Ceram solid, M.p. > 350°C, IR (KBr, cm–1): ν = 3404, 3188, 2945, 2233, 1618, 1481, 1379 and 1116. 1H NMR (400 MHz, DMSO-d6) δ = 12.23 (s, 1H), 9.84 (s, 1H), 7.37 (t, J = 8.9 Hz, 3H), 7.18 (d, J = 8.9 Hz, 1H), 6.94 (dd, J = 8.2, 1.5 Hz, 1H), 6.84–6.76 (m, 2H), 6.38 (d, J = 9.0 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ = 162.0, 160.5, 158.8, 157.3, 152.0, 136.6, 135.1, 129.9, 118.9, 116.4, 116.3, 115.1, 107.2, 104.3, 97.3. ESI-mass: m/z = 278.
7-Amino-4-(3-ethoxy-4-hydroxyphenyl)-2-hydroxy-3,4-dihydro-1,8-naphthyridine-3-carbonitrile (4l) Ceram solid, M.p. > 350°C, IR (KBr, cm–1): ν = 3469, 3351, 3236, 2976, 2256, 2219, 1684, 1629, 1520, 1473, 1355 and 1042. 1H NMR (400 MHz, DMSO-d6) δ = 10.69 (d, J = 9.2 Hz, 1H), 8.98 (d, J = 15.2 Hz, 1H), 6.96–6.91 (m, 1H), 6.83–6.76 (m, 1H), 6.74–6.69 (m, 1H), 6.59–6.48 (m, 1H), 6.12–5.93 (m, 3H), 4.81 (d, J = 12.9 Hz, 1H), 4.37–4.29 (m, 1H), 4.02–3.92 (m, 2H), 1.31 (t, J = 7.0 Hz, 3H). 13C NMR (100 MHz, DMSO-d6) δ = 163.6, 158.3, 148.0, 146.9, 146.3, 137.9, 137.1, 130.3, 128.9, 121.2, 119.5, 117.0, 116.6, 115.6, 115.5, 113.5, 106.9, 106.4, 102.8, 102.4, 63.7, 42.9, 41.8, 14.6. ESI-mass: m/z = 324.
7-Amino-4-(4-chlorophenyl)-2-hydroxy-3,4-dihydro-1,8-naphthyridine-3-carbonitrile (4m) Yellow solid, M.p. > 350°C, IR (KBr, cm–1): ν = 3395, 3344, 3163, 2223, 1623, 1477, 1378 and 1092. 1H NMR (250 MHz, DMSO-d6) δ = 10.72 (s, 1H), 7.32 (t, J = 39.2 Hz, 5H), 6.42 (s, 1H), 5.98 (s, 2H), 4.90 (d, J = 37.3 Hz, 1H), 4.47 (s, 1H). 13C NMR (62.5 MHz, DMSO-d6) δ = 163.7, 163.4, 159.2, 158.9, 148.6, 139.0, 138.5, 138.0, 137.4, 132.9, 131.0, 129.8, 129.4, 117.2, 116.8, 106.4, 103.5, 102.9, 43.0, 41.8. ESI-mass: m/z = 298.