sulfanilamido-guanidina (82) [52]

1,04 g di sulfanilammide (0.006 moli) vengono solubilizzati in 1,6 ml di HCl conc., vengono quindi addizionati 2.4 ml di cianamide (50% p/p soluzione acquosa) (0.058 moli) e si scalda a 100 °C per 30 minuti. Dopo raffreddamento la soluzione ottenuta è versata in un becker contenente una soluzione satura di NaHCO3 e tenuta

in freezer tutta la notte. Si forma un precipitato che viene poi raccolto mediante filtrazione sottovuoto e che corrisponde a 0.739 g di prodotto 82 desiderato. Resa: 45 %.

4-[(7,7-dimetil-5-oxo-5,6,7,8-tetraidrochinazolin-2- il)amino]benzenesolfonammide (78b)

Il composto 81 (0.195 g, 0.0010 moli) è solubilizzato nell’opportuna quantità di n- BuOH e addizionato di 0.300 g (0.0010 moli) del composto 82 e di 0.080 g (0.0020 moli) di NaOH. La miscela di reazione viene scaldata a 120 °C per 16 ore

91 controllando l’andamento mediante TLC (miscela eluente: etere di petrolio 40- 60/acetato di etile = 1:9). Dopo raffreddamento il solido ottenuto viene raccolto mediante filtrazione sottovuoto e purificato tramite cristallizzazione da etanolo. Resa: 40 % P.f.: 257-260 °C 1_{H NMR (400 MHz, DMSO-d} 6): δ 1.03 (s, 6H), 2.48 (s, 2H), 2.86 (s, 2H), 7.76 (d, J = 8.0 Hz, 2H), 7.96 (d, J = 8.0 Hz, 2H), 8.84 (s, 1H); 13_{C NMR (100 MHz, DMSO-} d6): δ 27.78 (2C), 32.29, 44.86, 51.05, 117.69, 119.18 (2C), 126.50 (2C), 137.61, 142.38, 157.31, 160.68, 172.30, 194.98.

Sintesi dei derivati 4-((7,7-dimetil-5-oxo-5,6,7,8-tetraidrochinazolin-2- il)amino)-N-fenilbenzenesolfonammidici (79a-i)

Procedura generale

Il composto 78b (0,190 g, 0,545 mmoli) è addizionato di 0,005g (0,027 mmoli) di CuI, 0,655 mmoli dell’opportuno iodobenzene, 0,188g (1,364 mmoli) di K2CO3,

0,03 ml di N,N’-dimetiletilendiammina (DMEDA) solubilizzati in 3 ml di Acetonitrile . La reazione viene condotta in corrente di N2 e scaldata a 100 °C,

mantenendola in agitazione, per un periodo che va da 8 a 24 ore, controllandone

l’andamento mediante T.L.C. (miscela eluente: etere di petrolio 40-60/acetato di etile = 5:5). Dopo raffreddamento la sospensione ottenuta viene filtrata a pressione ridotta ottenendo i composti solidi grezzi che vengono purificati mediante cromatografia flash su gel di silice (diametro: 3 cm, altezza: 17 cm, miscela eluente: etere di petrolio 40-60/acetato di etile = 5:5).

92 4-((7,7-dimetil-5-oxo-5,6,7,8-tetraidrochinazolin-2-il)amino)-N- fenilbenzenesolfonammide (79a) Resa: 20 % P.f.: 215-217 °C 1_{H NMR (400 MHz, DMSO-d} 6): δ 1.03 (s, 6H), 2.46 (s, 2H), 2.86 (s, 2H), 3.65 (s, 3H), 6.98-7.02 (m, 1H), 7.09 (d, J = 7.6 Hz, 2H), 7.21-7.24 (m, 2H), 7.70 (d, J = 8.8 Hz, 2H), 7.95 (d, J = 8.8 Hz, 2H), 8.84 (s, 1H), 10.17 (s, 1H, scamb.), 10.68 (s, 1H, scamb); 13C NMR (100 MHz, DMSO-d6): δ 27.75, 35.55, 37.13, 51.44, 119.75, 120.25, 123.64, 124.40, 128.29, 129.36, 137.52, 138.53, 138.64, 141.54, 149.44, 192.13. 4-((7,7-dimetil-5-oxo-5,6,7,8-tetraidrochinazolin-2-il)amino)-N-(4- metossifenil)benzenesolfonammide (79b) Resa: 25 % P.f.: 210-212 °C 1_{H NMR (400 MHz, DMSO-d} 6): δ 1.03 (s, 6H), 2.50 (s, 2H), 2.86 (s, 2H), 3.65 (s, 3H), 6.79 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.93 (d, J = 8.8 Hz, 2H), 8.84 (s, 1H), 9.80 (s, 1H, scamb.), 10.66 (s, 1H, scamb); 13_{C NMR (100 MHz, DMSO-d} 6): δ 27.85, 32.38, 51.07, 55.19, 114.32, 119.07, 123.24, 127.82, 129.21, 130.50, 138.07, 143.20, 152.95, 153.85, 160.65, 166.42, 172.33, 195.09. 4-((7,7-dimetil-5-oxo-5,6,7,8-tetraidrochinazolin-2-il)amino)-N-(4- clorofenil)benzenesolfonammide (79c)

93 Resa: 20 % P.f.: 235-237 °C 1_{H NMR (400 MHz, DMSO-d} 6): δ 1.03 (s, 6H), 2.48 (s, 2H), 2.86 (s, 2H), 7.10 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 8.4 Hz, 2H), 7.96 (d, J = 8.8 Hz, 2H), 8.84 (s, 1H), 10.834 (bs, 1H, scamb.), 10.69 (s, 1H, scamb); 13C NMR (100 MHz, DMSO-d6): δ 27.77, 32.30, 44.96, 51.08, 117.92, 119.18, 121.40, 127.79, 127.89, 129.09, 132.54, 136.99, 143.55, 157.27, 160.56, 172.35, 195.09. 4-((7,7-dimetil-5-oxo-5,6,7,8-tetraidrochinazolin-2-il)amino)-N-(4- tolil)benzenesolfonammide (79d) Resa: 15 % P.f.: 246-248 °C 1_{H NMR (400 MHz, DMSO-d} 6): δ 1.03 (s, 6H), 2.17 (s, 3H), 2.49 (s, 2H), 2.86 (s, 2H), 6.99 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 8.4 Hz, 2H), 7.93 (d, J = 8.6 Hz, 2H), 8.84 (s, 1H), 10.01 (s, 1H, scamb.), 10.67 (s, 1H, scamb); 13_{C NMR (100 MHz, DMSO-d} 6): δ 20.37, 27.86, 32.40, 45.87, 51.18, 118.98, 119.17, 120.45, 126.07, 127.84, 129.62, 130.26, 143.38, 143.78, 144.39, 157.18, 157.36, 194.96. 4-((7,7-dimetil-5-oxo-5,6,7,8-tetraidrochinazolin-2-il)amino)-N-(4- nitrofenil)benzenesolfonammide (79e) Resa: 20 % P.f.: 264-266 °C

94 1_{H NMR (400 MHz, DMSO-d} 6): δ 1.04 (s, 6H), 2.49 (s, 2H), 2.87 (s, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 8.8 Hz, 2H), 8.02(d, J = 9.2 Hz, 2H), 8.13-8,15 (m, 2H), 8.85 (s, 1H), 10.74 (s, 1H, scamb.), 11.19 (s, 1H, scamb); 13C NMR (100 MHz, DMSO-d6): δ 27.72, 32.26, 44.80, 51.01, 117.72, 117.94, 119.26, 125.32, 127.92, 131.60, 142.31, 143.97, 144.41, 157.21, 160.48, 172.27, 194.96. 4-((7,7-dimetil-5-oxo-5,6,7,8-tetraidrochinazolin-2-il)amino)-N-(3- metossifenil)benzenesolfonammide (79f) Resa: 15 % P.f.: 209-211 °C 1_{H NMR (400 MH z, DMSO-d} 6): δ 1.03 (s, 6H), 2.56 (s, 2H), 2.86 (s, 2H), 3.70 (s, 3H), 6.56-6.59 (m, 1H), 6.67-6.68 (m, 2H), 7.11 (t, 1H), 7.22 (d, J = 8.8 Hz, 2H), 7.96 (d, J = 8.8 Hz, 2H), 8.84 (s, 1H), 10.20 (s, 1H, scamb.), 10.69 (s, 1H, scamb); 13_{C NMR (100 MHz, DMSO-d} 6): δ 27.86, 32.37, 51.09, 55.18, 106.73, 114.45, 116.42, 118.27, 119.78, 123.89, 127.13, 130.76, 139.47, 143.36, 156.31, 169.16, 186.75, 189.12, 193.14 4-((7,7-dimetil-5-oxo-5,6,7,8-tetraidrochinazolin-2-il)amino)-N-(3- clorofenil)benzenesolfonammide (79g) Resa: 15 % P.f.: 229-231 °C 1_{H NMR (400 MHz, DMSO-d} 6): δ 1.03 (s, 6H), 2.49 (s, 2H), 2.86 (s, 2H), 7.03- 7.12 (m, 3H), 7.26 (t, J = 8.0 Hz, 1H), 7.73 (d, J = 8.8 Hz, 2H), 7.98 (d, J = 8.8 Hz, 2H), 8.85 (s, 1H), 10.50 (s, 1H, scamb.), 10.72 (s, 1H, scamb); 13C NMR (100 MHz,

95 DMSO-d6): δ 27.78, 32.29, 36.09, 42.54, 110.90, 117.88, 118.78, 119.32, 120.91, 127.75, 131.05, 133.29, 143.69, 145.53, 160.42, 172.28, 189.92, 195.05, 197.16. 4-((7,7-dimetil-5-oxo-5,6,7,8-tetraidrochinazolin-2-il)amino)-N-(3- tolil)benzenesolfonammide (79h) Resa: 15 % P.f.: 218-220°C 1_{H NMR (400 MHz, DMSO-d} 6): δ 1.07 (s, 6H), 2.19 (s, 3H), 2.46 (s, 2H), 2.86 (s, 2H), 6.80-6.82 (m, 1H), 6.89-6.91 (m, 2H), 7.07-7.09 (m, 1H), 7.70 (d, J = 8.0 Hz, 2H), 7.95 (d, J = 7.6 Hz, 2H), 8.84 (s, 1H), 10.13 (s, 1H, scamb.), 10.69 (s, 1H, scamb); 13C NMR (100 MHz, DMSO-d6): δ 20.38, 27.84, 32.41, 45.85, 51.17, 111.12, 118.89, 119.722, 120.13, 121.17, 124.83, 128.11, 131.36, 140.26, 143.38, 157.26, 169.15, 173.78, 189.21, 194.37. 4-((7,7-dimetil-5-oxo-5,6,7,8-tetraidrochinazolin-2-il)amino)-N-(3- nitrofenil)benzenesolfonammide (79i) Resa: 20 % P.f.: 241-243 °C 1_{H NMR (400 MHz, DMSO-d} 6): δ 1.03 (s, 6H), 2.48 (s, 2H), 2.86 (s, 2H), 7.53- 7.54 (m, 2H), 7.76 (d, J = 9.2 Hz, 2H), 7.84-7.87 (m, 1H), 7.95-8.00 (m, 3H), 8.84 (s, 1H), 10.72 (s, 1H, scamb.), 10.85 (s, 1H, scamb); 13C NMR (100 MHz, DMSO- d6): δ 27.71, 32.24, 44.82, 51.03, 110.67, 116.46, 118.39, 118.96, 121.03, 126.78,

96

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