Pyridine → HCID 10547930, compound

Participants

Reaction Conditions

Reaction Steps

3,N-(N,N-Dimethylaminopropyl)-1,N-ethylcarbodiimide hydrochloride (EDAC.HCl) (385 mg, 2.0 mmol) was added in one portion to a solution of 6-amino-4-(4-phenoxyanilino)quinazoline (328 mg, 1.0 mmol), acrylic acid (148 mg, 2.04 mmol), and pyridine (165 mg, 2.1 mmol) in THF (10 mL) stirred under nitrogen at 0° C. After 4 hours at 0° C., tlc (10% MeOH/CHCl3) showed considerable SM, so the reaction mixture was stirred at 25° C. for 2 hours. The mixture was recooled to 0° C., and water (2 mL) was added dropwise. This solution was poured onto rapidly stirred ice-water (40 mL), the pH was raised to 7 with saturated Na2CO3 solution, and the very fine ppt was allowed to settle, collected by Buchner filtration, rinsed with water (2×10 mL), and dried in a vacuum oven at 65° C. for 4 hours. The pale yellow solid was refluxed and sonicated in EtOAc (10 mL), filtered, and the filtrate was eluted through a small silica gel plug with EtOAc. The combined washings were stripped rigourously at 25° C. under vacuum to give N-(4-[4-phenoxyanilino]quinazolin-6-yl)acrylamide (162 mg, 41%) as a pale yellow glass; mp 185-191° C.

Provenance & Evidence