Diisopropylethylamine → 4-[(3-Bromophenyl)amino]-6-[(4-{N-[(ethoxycarbonyl)methyl]-N-methylamino}-1-oxo-2-buten-1-yl)-amino]-quinazoline

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Reaction Steps

13.94 ml of Hünig base are pipetted into a suspension of 9.37 g of sarcosine ethylester hydrochloride in 25 ml of tetrahydrofuran while cooling with an ice bath. Then a solution of 2.00 g of 4-[(3-bromophenyl)amino]-6-[(4-bromo-1-oxo-2-buten-1-yl)amino]-quinazoline in 10 ml of dimethylformamide is added dropwise within 15 minutes. The reaction mixture is allowed to come up to ambient temperature overnight in an ice bath. For working up, 25 ml of saturated sodium hydrogen carbonate solution and 50 ml of ethyl acetate are added. The organic phase is separated off and the aqueous phase is extracted with ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over magnesium sulphate and concentrated by evaporation. The dark-brown oily residue is stirred with 50 ml of water, the precipitate formed is suction filtered and washed with water. The crude product is purified by chromatography on a silica gel column with methylene chloride/methanol (50:1 to 20:1). Yield: 1.00 g (46% of theory), Melting point: 182-183° C. Mass spectrum (ESI*): m/z=496, 498 [M−H]*

Provenance & Evidence