反应详情

tert-Butyl[5-({7-methoxy-8-[3-(morpholin-4-ylsulfonyl)propoxy]-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl}carbamoyl)pyrimidin-2-yl]carbamate (Step 1, 150 mg 0.26 mmol) was dissolved in CH2Cl2 (15 mL) and TFA (0.16 mL, 2.1 mmol) was added dropwise. The mixture was stirred at rt over 2 d, after which 5 drops of Et3N were added causing a solid to precipitate. The mixture was stirred overnight, then the solvents removed under reduced pressure. The resulting residue was triturated in EtOAc (15 mL), collected by vacuum filtration and washed further with EtOAc (10 mL). This solid was then triturated in water (5 mL) collected by vacuum filtration and washed further with water (10 mL). High vacuum drying gave the title compound (172 mg, 92%): HPLC MS RT=0.87 min, MH+=545.2; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 2.21-2.26 (2H, m), 3.15-3.18 (4H, m), 3.24-3.29 (2H, m), 3.61-3.65 (4H, m), 3.99 (3H, s), 4.18-4.25 (2H, m), 4.37 (2H, t), 4.48-4.55 (2H, m), 7.44 (1H, d), 8.02 (1H, d), 9.06 (2H, s).

1. customto precipitate
2. stirringThe mixture was stirred overnight
3. customthe solvents removed under reduced pressure
4. customThe resulting residue was triturated in EtOAc (15 mL)
5. filtrationcollected by vacuum filtration
6. washwashed further with EtOAc (10 mL)
7. customThis solid was then triturated in water (5 mL)
8. filtrationcollected by vacuum filtration
9. washwashed further with water (10 mL)
10. customHigh vacuum drying