反应详情

温度

120 °C

To N-(8-hydroxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide (Example 2-5 in WO2004029055, 250 mg, 0.001 mol) and K2CO3 (1.1 g, 0.008 mol) in DMF (5 ml) was added 4-[(3-chloropropyl)sulfonyl]morpholine (Intermediate E, 204.0 mg, 0.001 mol) to a sealed tube and heated to 120° C. for 3 h. The reaction was poured into water and extracted with CH2Cl2. Organic layers dried with MgSO4, filtered and concentrated. The residue was purified using silica gel flash chromatography (100% EtOAc, then 0-20% MeOH/CH2Cl2) to provide the title compound (130 mg, 33%). TLC: Rf=0.21 in 10% MeOH/CH2Cl2, HPLC MS RT=1.81 min., MW=499.1; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 2.22 (2H, m), 3.17 (4H, m), 3.26 (2H, m), 3.64 (4H, m), 4.18-4.29 (4H, m), 4.56 (2H, m), 7.22 (1H, d), 7.74 (1H, s), 7.89 (1H, m), 8.12 (1H, d), 8.81 (1H, m), 8.95 (1H, dd), 9.44 (1H, s).

1. extractionextracted with CH2Cl2
2. dry with materialOrganic layers dried with MgSO4
3. filtrationfiltered
4. concentrationconcentrated
5. customThe residue was purified