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Isobutyl chloroformate (20.35 g, 0.15 mol) was added dropwise over 20 minutes to a solution of acrylic acid (10.82 g), 0.15 mol) and triethylamine (30.19 g, 0.30 mol) in THF (400 mL), stirred under nitrogen at 0° C. The slurry was stirred at that temperature for 30 minutes, and then 6-amino-4[(3-methylphenyl)amino]quinazoline (27.71 g, 107 mmol) in DMF (80 mL) was added dropwise over 45 minutes. After a further 4 hours, further mixed anhydride (from acrylic acid (3.61 g, 50 mmol), isobutyl chloroformate (6.80 g, 50 mmol) and triethylamine (10.1 g, 100 mmol) in THF (100 mL) at 0° C.) was added in one portion. After a further 15 minutes, the reaction mixture was stirred at 25° C. for 30 minutes, and then poured onto ice-water (1 L). Ether (200 mL) was added and the phases were separated. The aqueous phase was extracted with EtOAc (500 mL), and the combined organic phases were washed with water (500 mL), and saturated brine (250 mL). The solution was stirred with anhydrous MgSO4 for 2 minutes, filtered, and silica gel (150 g) was added. The mixture was stripped to dryness, and used as the origin of a flash silica chromatography column (700 g), eluting with acetone/dichloromethane (25% 4 L, 35% 8 L, 40% 4 L). The solvent was stripped from the appropriate fractions and the residue was suspended in EtOAc (200 mL) refluxed for 5 minutes and sonicated at 60° C. for 20 minutes, then collected by Buchner filtration, rinsed with EtOAc (3×25 mL), and dried in a vacuum oven at 75° C. for 16 hours, to give N-[4-[(3-methyl-phenyl)amino]quinazolin-6-yl]acrylamide (11.38 g, 35%) as a light yellow solid, mp 247-8° C.

1. stirringThe slurry was stirred at that temperature for 30 minutes
2. waitAfter a further 15 minutes
3. stirringthe reaction mixture was stirred at 25° C. for 30 minutes
4. additionpoured onto ice-water (1 L)
5. customthe phases were separated
6. extractionThe aqueous phase was extracted with EtOAc (500 mL)
7. washthe combined organic phases were washed with water (500 mL), and saturated brine (250 mL)
8. stirringThe solution was stirred with anhydrous MgSO4 for 2 minutes
9. filtrationfiltered
10. additionsilica gel (150 g) was added
11. washeluting with acetone/dichloromethane (25% 4 L, 35% 8 L, 40% 4 L)
12. temperaturerefluxed for 5 minutes
13. customsonicated at 60° C. for 20 minutes
14. filtrationcollected by Buchner filtration
15. washrinsed with EtOAc (3×25 mL)
16. customdried in a vacuum oven at 75° C. for 16 hours