6
78
N-(3-Chloro-4-fluorophenyl)-7[methoxy-6-[(3-morpholin-4-yl) propoxy]-quinazolin-4-yl] amine (7)
6
-(3-Chloropropoxy)-N-(3-chloro-4-fluorophenyl)-7-methoxyquinazolin-4-amine (22, 87.5 g, 0.22
mol) and potassium iodide (2.0 g) were added to the solution of morpholine (43 g, 0.5 mol) in DMF
200 mL). The solution was stirred at 60 °C for 30 min, then poured into ice-water (2 L) and extracted
(
with chloroform (3 × 300 mL). The organic layers were combined, washed with a saturated solution of
sodium carbonate (2 × 200 mL) and brine (1 × 100 mL) and then dried (Na SO ). The solvent was
2
4
removed under vacuum. The crude product was crystallized from ethyl acetate to afford compound 7
1
(
(
76.5 g, 78% yield, 99.6% HPLC purity); mp: 119-120°C; H-NMR: 2.43 (tt, 2H, -CH
2
CH
2
CH
2
-), 2.64
m, 4H,), 2.73 (t, 2H,-CH ), 3.82 (m, 4H, ), 4.02 (s,3H, -OCH ), 4.26 (t, 2H, -OCH ), 7.13 (s, 1H,
2
3
2
HAr), 7.29 (s, 1H, HAr), 7.49 (s, 1H, HAr), 7.61 (d, 1H, HAr), 7.98 (d, 1H, HAr), 8.66 (s, 1H, HAr),
1
3
1
1
1
0.44-10.80 (b, 1H, -NH-); C-NMR: 26.23, 53.79, 55.40, 56.22, 60.39, 61.67, 66.95, 67.76, 100.79,
08.19, 109.04, 118.07, 122.71, 123.13, 135.18, 136.18, 147.67, 149.15, 153.63, 155.30, 156.47,
+
62.74.; MS m/z: 447.1 ([M+H] , 100%).
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Sample availability: Samples of compounds 16-21 are available from the authors.
2007 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.
©